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SAPHNELO™

SAPHNELO

(anifrolumab-fnia)

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Highlights of Prescribing Information

<?xml version="1.0" encoding="UTF-8"?><title>These highlights do not include all the information needed to use SAPHNELO<sup>®</sup> safely and effectively. See full prescribing information for SAPHNELO.<br/>SAPHNELO (anifrolumab-fnia) injection, for intravenous, or subcutaneous use<br/>Initial U.S. Approval: 2021</title>

SPL product data elements section
RECENT MAJOR CHANGES SECTION
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
6 ADVERSE REACTIONS
7 DRUG INTERACTIONS
8 USE IN SPECIFIC POPULATIONS
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
13 NONCLINICAL TOXICOLOGY
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
SPL PATIENT PACKAGE INSERT SECTION
INSTRUCTIONS FOR USE SECTION
INSTRUCTIONS FOR USE SECTION
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

SPL product data elements section

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<?xml version="1.0" encoding="UTF-8"?><section ID="ID_AC87E54B-D573-497C-B999-135F66DF81D8"> <id root="f2a3e675-cf4c-4818-bf6b-d13b31e8d9a6"/> <code code="43683-2" codeSystem="2.16.840.1.113883.6.1" displayName="RECENT MAJOR CHANGES SECTION"/> <effectiveTime value="20260424"/> <excerpt> <highlight> <text> <paragraph/> <paragraph>Dosage and Administration (<linkHtml href="#ID_09900799-953e-499f-9f97-fe2a797a3e58">2</linkHtml>) 04/2026</paragraph> </text> </highlight> </excerpt> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_8af3bc2a-f1a6-4e1f-ba08-85805e2ef822"> <id root="24ab7780-01a6-4a3d-94ba-a23d78c3051a"/> <code code="34067-9" codeSystem="2.16.840.1.113883.6.1" displayName="INDICATIONS & USAGE SECTION"/> <title>1 INDICATIONS AND USAGE </title> <text> <paragraph>SAPHNELO is indicated for the treatment of adult patients with moderate to severe systemic lupus erythematosus (SLE), who are receiving standard therapy.</paragraph> <paragraph> <content styleCode="underline">Limitations of Use</content> </paragraph> <paragraph>The efficacy of SAPHNELO has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Use of SAPHNELO is not recommended in these situations.</paragraph> </text> <effectiveTime value="20260424"/> <excerpt> <highlight> <text> <paragraph>SAPHNELO is a type I interferon (IFN) receptor antagonist indicated for the treatment of adult patients with moderate to severe systemic lupus erythematosus (SLE), who are receiving standard therapy. (<linkHtml href="#ID_8af3bc2a-f1a6-4e1f-ba08-85805e2ef822">1</linkHtml>)</paragraph> <paragraph> <content styleCode="underline">Limitations of Use:</content> The efficacy of SAPHNELO has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Use of SAPHNELO is not recommended in these situations. (<linkHtml href="#ID_8af3bc2a-f1a6-4e1f-ba08-85805e2ef822">1</linkHtml>)</paragraph> </text> </highlight> </excerpt> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_09900799-953e-499f-9f97-fe2a797a3e58"> <id root="c0a078e0-a934-4a7d-b363-7e70b4a5a290"/> <code code="34068-7" codeSystem="2.16.840.1.113883.6.1" displayName="DOSAGE & ADMINISTRATION SECTION"/> <title>2 DOSAGE AND ADMINISTRATION </title> <effectiveTime value="20260424"/> <excerpt> <highlight> <text> <list listType="unordered"> <item> <caption>•</caption>The recommended intravenous dosage is 300 mg every 4 weeks. (<linkHtml href="#ID_63aa4842-0c00-4352-a8b7-c7026d3bedf8">2.2</linkHtml>) </item> <item> <caption>•</caption>The recommended subcutaneous dosage is 120 mg once every week. (<linkHtml href="#ID_63aa4842-0c00-4352-a8b7-c7026d3bedf8">2.2</linkHtml>)</item> <item> <caption>•</caption>See Full Prescribing Information for complete preparation and administration information. (<linkHtml href="#ID_9f3f7989-b79f-498f-a0a0-06780f8197e7">2.3</linkHtml>, <linkHtml href="#ID_81c9195e-4190-46c4-9b2d-a748e67db692">2.4</linkHtml>)</item> </list> </text> </highlight> </excerpt> <component> <section ID="ID_2282b273-e988-4c58-8035-dc5b5296d5ac"> <id root="13e6ab6a-aa7f-4a8e-843b-1fc3a77099c9"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>2.1 Important Administration Information </title> <text> <paragraph> <content styleCode="xmChange">SAPHNELO is intended for use under the guidance of a healthcare provider and may be administered as an intravenous infusion or as a subcutaneous injection.</content> </paragraph> <paragraph> <content styleCode="xmChange">SAPHNELO vials are for intravenous use only and must be diluted prior to intravenous administration <content styleCode="italics">[see <linkHtml href="#ID_9f3f7989-b79f-498f-a0a0-06780f8197e7">Dosage and Administration (2.3)</linkHtml>]</content>.</content> </paragraph> <paragraph> <content styleCode="xmChange">SAPHNELO prefilled syringe and autoinjector (SAPHNELO PEN) are for subcutaneous use only <content styleCode="italics">[see <linkHtml href="#ID_81c9195e-4190-46c4-9b2d-a748e67db692">Dosage and Administration (2.4)</linkHtml>]</content>.</content> </paragraph> </text> <effectiveTime value="20260424"/> </section> </component> <component> <section ID="ID_63aa4842-0c00-4352-a8b7-c7026d3bedf8"> <id root="15dc73a6-9134-4984-92c3-369fe13a2945"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>2.2 Recommended Dosage </title> <text> <paragraph> <content styleCode="xmChange">The recommended dosage of SAPHNELO is:</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="xmChange">300 mg, administered as an intravenous infusion over a 30‑minute period every 4 weeks; or</content> </item> <item> <caption>•</caption> <content styleCode="xmChange">120 mg, administered as a subcutaneous injection once every week.</content> </item> </list> <paragraph> <content styleCode="xmChange"> <content styleCode="underline">Missed Dose</content> </content> </paragraph> <paragraph> <content styleCode="xmChange">If a planned intravenous infusion is missed, administer SAPHNELO as soon as possible. Maintain a minimum interval of 14 days between infusions.</content> </paragraph> <paragraph> <content styleCode="xmChange">If a planned subcutaneous dose is missed, instruct the patient to administer SAPHNELO as soon as they remember. Thereafter, instruct the patient to start a new weekly schedule from the day the missed dose was administered or resume dosing on their usual day of administration, providing a minimum interval of 3 days between subcutaneous injections.</content> </paragraph> </text> <effectiveTime value="20260424"/> </section> </component> <component> <section ID="ID_9f3f7989-b79f-498f-a0a0-06780f8197e7"> <id root="ec6833b4-dba7-4db7-895e-9a5fa9c0c915"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>2.3 Intravenous Preparation and Administration Instructions </title> <text> <paragraph>SAPHNELO is supplied as a single-dose vial. Prepare the diluted infusion solution using aseptic technique, by the following procedure:</paragraph> <list listType="ordered"> <item> <caption>1.</caption>Visually inspect the vial for particulate matter and discoloration. SAPHNELO is a clear to opalescent, colorless to slightly yellow, solution. Discard the vial if the solution is cloudy, discolored or visible particles are observed. Do not shake the vial.</item> <item> <caption>2.</caption>Withdraw and discard 2 mL of solution from a 50 mL or 100 mL 0.9% Sodium Chloride Injection, USP infusion bag.</item> <item> <caption>3.</caption>Withdraw 2 mL of solution from the vial of SAPHNELO and add it to the infusion bag. Mix the solution by gentle inversion. Do not shake.</item> <item> <caption>4.</caption>Each vial is intended for one time use only. Discard any unused portion remaining in the vial.</item> <item> <caption>5.</caption>Administer the infusion solution immediately after preparation.</item> <item> <caption>6.</caption>If the infusion solution is not administered immediately, store the diluted solution of SAPHNELO at room temperature 59°F to 77°F (15°C to 25°C) for up to 4 hours, or refrigerated 36°F to 46°F (2°C to 8°C) for up to 24 hours. Do not freeze. Protect from light. If refrigerated, allow the diluted SAPHNELO solution to reach room temperature prior to administration.</item> <item> <caption>7.</caption>Administer the infusion solution intravenously over a 30-minute period through an infusion line containing a sterile, low-protein binding 0.2 to 15 micron in-line or add-on filter.</item> <item> <caption>8.</caption>To ensure the complete dose of SAPHNELO has been administered, flush the entire infusion line with 25 mL of 0.9% Sodium Chloride Injection, USP at the end of the infusion.</item> <item> <caption>9.</caption>Do not co-administer other medicinal products through the same infusion line.</item> <item> <caption>10.</caption>Dispose of any unused medicinal product or waste material in accordance with local requirements<content styleCode="xmChange">.</content> </item> </list> </text> <effectiveTime value="20260424"/> </section> </component> <component> <section ID="ID_81c9195e-4190-46c4-9b2d-a748e67db692"> <id root="8b2e39ea-285b-4005-9e24-0139c90a3e66"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>2.4 Subcutaneous Preparation and Administration Instructions </title> <text> <paragraph> <content styleCode="xmChange">The SAPHNELO prefilled syringe and autoinjector (SAPHNELO PEN) are for subcutaneous use.</content> </paragraph> <list listType="ordered"> <item> <caption>1.</caption> <content styleCode="xmChange">Comprehensive instructions for subcutaneous administration of SAPHNELO using the prefilled syringe or autoinjector are provided in the ‘Instructions for Use’.</content> </item> <item> <caption>2.</caption> <content styleCode="xmChange">Patients/caregivers may administer SAPHNELO prefilled syringe/SAPHNELO PEN after proper training in the subcutaneous injection technique and after the healthcare provider determines it is appropriate.</content> </item> <item> <caption>3.</caption> <content styleCode="xmChange">Prior to administration, remove SAPHNELO from the refrigerator and allow it to come to room temperature for 60 minutes.</content> </item> <item> <caption>4.</caption> <content styleCode="xmChange">Visually inspect SAPHNELO for particulate matter and discoloration prior to administration. SAPHNELO is a clear to opalescent, colorless to slightly yellow, solution. Discard the prefilled syringe or autoinjector if the solution is cloudy, discolored or visible particles are observed.</content> </item> <item> <caption>5.</caption> <content styleCode="xmChange">Administer the subcutaneous injection into the thigh or abdomen, avoiding the 5 cm (approximately 2 inches) area around the navel. The upper arm can also be used if a healthcare professional or caregiver administers the injection.</content> </item> <item> <caption>6.</caption> <content styleCode="xmChange">Do not inject into areas where the skin is tender, bruised, erythematous or hardened. When injecting in the same region, advise patients to use an injection site at least 3 cm (1‑inch) away from the last injection site.</content> </item> <item> <caption>7.</caption> <content styleCode="xmChange">Dispose of any unused medicinal product or waste material in accordance with local requirements.</content> </item> </list> </text> <effectiveTime value="20260424"/> </section> </component> <component> <section ID="ID_81ea23a8-2ae5-4bc3-8bee-390329604b66"> <id root="e85616df-69d6-45e0-8721-6b339c1582c1"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>2.5 Switching Between Intravenous and Subcutaneous Administration </title> <text> <paragraph> <content styleCode="xmChange">When transitioning patients from intravenous administration to subcutaneous administration of SAPHNELO, administer the first subcutaneous injection approximately 2 weeks after the last intravenous infusion.</content> </paragraph> <paragraph> <content styleCode="xmChange">When transitioning patients from subcutaneous administration to intravenous administration of SAPHNELO, administer the first intravenous infusion approximately 3 to 4 weeks after the last subcutaneous injection.</content> </paragraph> </text> <effectiveTime value="20260424"/> </section> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_eefa5e54-13da-46f9-8e66-0abbc39af0d8"> <id root="0bac35ea-2175-490f-8ca3-14bda8cea4bb"/> <code code="43678-2" codeSystem="2.16.840.1.113883.6.1" displayName="DOSAGE FORMS & STRENGTHS SECTION"/> <title>3 DOSAGE FORMS AND STRENGTHS </title> <text> <paragraph> <content styleCode="underline">Intravenous Infusion</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>Injection: 300 mg/2 mL (150 mg/mL) as a clear to opalescent, colorless to slightly yellow solution in a single-dose vial.</item> </list> <paragraph> <content styleCode="underline">Subcutaneous Injection</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>Injection: 120 mg/0.8 mL as a clear to opalescent, colorless to slightly yellow solution in a single-dose prefilled syringe or single-dose autoinjector (SAPHNELO PEN).</item> </list> </text> <effectiveTime value="20260424"/> <excerpt> <highlight> <text> <paragraph>Intravenous Infusion:</paragraph> <list listType="unordered"> <item> <caption>•</caption>Injection: 300 mg/2 mL (150 mg/mL) in a single-dose vial. (<linkHtml href="#ID_eefa5e54-13da-46f9-8e66-0abbc39af0d8">3</linkHtml>)</item> </list> <paragraph>Subcutaneous Injection:</paragraph> <list listType="unordered"> <item> <caption>•</caption>Injection: 120 mg/0.8 mL in a single-dose prefilled syringe or single-dose autoinjector (SAPHNELO PEN). (<linkHtml href="#ID_eefa5e54-13da-46f9-8e66-0abbc39af0d8">3</linkHtml>) </item> </list> </text> </highlight> </excerpt> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_6d3244c5-5a4f-4c5d-a045-f7617e984b8d"> <id root="61879c53-7264-4f0e-acad-1f7b162f1338"/> <code code="34070-3" codeSystem="2.16.840.1.113883.6.1" displayName="CONTRAINDICATIONS SECTION"/> <title>4 CONTRAINDICATIONS </title> <text> <paragraph>SAPHNELO is contraindicated in patients with a history of anaphylaxis with anifrolumab-fnia <content styleCode="italics">[see <linkHtml href="#ID_ac54e222-c42f-4bb9-ac2a-77059b3c7f5a">Warnings and Precautions (5.2)</linkHtml>]</content>.</paragraph> </text> <effectiveTime value="20260424"/> <excerpt> <highlight> <text> <paragraph>SAPHNELO is contraindicated in patients with a history of anaphylaxis with anifrolumab-fnia. (<linkHtml href="#ID_6d3244c5-5a4f-4c5d-a045-f7617e984b8d">4</linkHtml>)</paragraph> </text> </highlight> </excerpt> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_ffdc5663-db46-4b14-bfb7-da99e3dfc283"> <id root="119c2a6e-5c27-4bfc-beda-276a64f4d5cc"/> <code code="43685-7" codeSystem="2.16.840.1.113883.6.1" displayName="WARNINGS AND PRECAUTIONS SECTION"/> <title>5 WARNINGS AND PRECAUTIONS </title> <effectiveTime value="20260424"/> <excerpt> <highlight> <text> <list listType="unordered"> <item> <caption>•</caption>Serious Infections: Serious and sometimes fatal infections have occurred in patients receiving SAPHNELO. SAPHNELO increases the risk of respiratory infections and herpes zoster. Avoid initiating treatment during an active infection. Consider the individual benefit-risk if using in patients with severe or chronic infections. Consider interrupting therapy with SAPHNELO if patients develop a new infection during treatment. (<linkHtml href="#ID_0622efa7-563c-4bd1-a678-012b3c491247">5.1</linkHtml>)</item> <item> <caption>•</caption>Hypersensitivity Reactions Including Anaphylaxis: Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported. (<linkHtml href="#ID_ac54e222-c42f-4bb9-ac2a-77059b3c7f5a">5.2</linkHtml>)</item> <item> <caption>•</caption>Malignancy: Consider the individual benefit-risk in patients with known risk factors for malignancy prior to prescribing SAPHNELO. (<linkHtml href="#ID_a43e910e-e90a-496b-841d-fa189746063e">5.3</linkHtml>)</item> <item> <caption>•</caption>Immunizations: Avoid use of live or live-attenuated vaccines in patients receiving SAPHNELO. (<linkHtml href="#ID_74e712d3-7a99-4b92-8f3e-35f95c0b6b7c">5.4</linkHtml>)</item> <item> <caption>•</caption>Not Recommended for Use with Other Biologic Therapies. (<linkHtml href="#ID_36e47e80-c67a-4d42-9aae-29a7dc4417bb">5.5</linkHtml>)</item> </list> </text> </highlight> </excerpt> <component> <section ID="ID_0622efa7-563c-4bd1-a678-012b3c491247"> <id root="60fb9680-010a-4ebc-8d7e-ff71ad3c33ec"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>5.1 Serious Infections </title> <text> <paragraph>Serious and sometimes fatal infections (including COVID‑19) have occurred in patients receiving immunosuppressive agents, including SAPHNELO. In controlled trials, fatal infections occurred more frequently in patients receiving SAPHNELO <content styleCode="italics">[see <linkHtml href="#ID_ff61362d-6225-41fa-a1c4-05d3c488f884">Adverse Reactions (6.1)</linkHtml>]</content>.</paragraph> <paragraph>In controlled trials, SAPHNELO increased the risk of respiratory infections and herpes zoster (disseminated herpes zoster events have been reported) <content styleCode="italics">[see </content> <content styleCode="italics"> <linkHtml href="#ID_ff61362d-6225-41fa-a1c4-05d3c488f884">Adverse Reactions (6.1)</linkHtml> </content> <content styleCode="italics">]</content>.</paragraph> <paragraph>Avoid initiating treatment with SAPHNELO in patients with any clinically significant active infection until the infection is resolved or adequately treated. Consider the benefit and risk of administering SAPHNELO in patients with a chronic infection, a history of recurrent infections, or known risk factors for infection. Instruct patients to seek medical advice if signs or symptoms of a clinically significant infection occur. If a patient develops an infection or is not responding to standard anti-infective therapy while on SAPHNELO, monitor the patient closely and consider interrupting SAPHNELO until the infection resolves.</paragraph> </text> <effectiveTime value="20260424"/> </section> </component> <component> <section ID="ID_ac54e222-c42f-4bb9-ac2a-77059b3c7f5a"> <id root="e045a21b-05f6-4ef8-b065-4751aa108294"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>5.2 Hypersensitivity Reactions Including Anaphylaxis </title> <text> <paragraph>Serious hypersensitivity reactions (including anaphylaxis) have been reported following SAPHNELO administration <content styleCode="italics">[see <linkHtml href="#ID_6d3244c5-5a4f-4c5d-a045-f7617e984b8d">Contraindication (4)</linkHtml>]</content>. Events of angioedema have also been reported <content styleCode="italics">[see <linkHtml href="#ID_ff61362d-6225-41fa-a1c4-05d3c488f884">Adverse Reactions (6.1)</linkHtml>]</content>.</paragraph> <paragraph>Other hypersensitivity reactions and infusion-related reactions have occurred following administration of SAPHNELO <content styleCode="italics">[see <linkHtml href="#ID_ff61362d-6225-41fa-a1c4-05d3c488f884">Adverse Reactions (6.1)</linkHtml>]</content>. Consider pre-medication before infusion of SAPHNELO for patients with a history of these reactions.</paragraph> <paragraph>SAPHNELO should be administered by healthcare providers prepared to manage hypersensitivity reactions, including anaphylaxis, and infusion-related reactions. If a serious infusion-related or hypersensitivity reaction (e.g., anaphylaxis) occurs, immediately interrupt the administration of SAPHNELO and initiate appropriate therapy.</paragraph> </text> <effectiveTime value="20260424"/> </section> </component> <component> <section ID="ID_a43e910e-e90a-496b-841d-fa189746063e"> <id root="a43e910e-e90a-496b-841d-fa189746063e"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>5.3 Malignancy </title> <text> <paragraph>There is an increased risk of malignancies with the use of immunosuppressants. The impact of SAPHNELO treatment on the potential development of malignancies is not known.</paragraph> <paragraph>Consider the individual benefit-risk in patients with known risk factors for the development or reoccurrence of malignancy prior to prescribing SAPHNELO. In patients who develop malignancies, consider the benefit-risk of continued treatment with SAPHNELO.</paragraph> </text> <effectiveTime value="20210730"/> </section> </component> <component> <section ID="ID_74e712d3-7a99-4b92-8f3e-35f95c0b6b7c"> <id root="b7321c4e-2f20-44f6-ab62-410bb02bf9cd"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>5.4 Immunizations </title> <text> <paragraph>Update immunizations, according to current immunization guidelines, prior to initiating SAPHNELO therapy. Avoid concurrent use of live or live-attenuated vaccines in patients treated with SAPHNELO.</paragraph> </text> <effectiveTime value="20260424"/> </section> </component> <component> <section ID="ID_36e47e80-c67a-4d42-9aae-29a7dc4417bb"> <id root="36e47e80-c67a-4d42-9aae-29a7dc4417bb"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>5.5 Not Recommended for Concomitant Use with Other Biologic Therapies </title> <text> <paragraph>SAPHNELO has not been studied in combination with other biologic therapies, including B-cell-targeted therapies. Therefore, use of SAPHNELO is not recommended for use in combination with biologic therapies.</paragraph> </text> <effectiveTime value="20210730"/> </section> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_e08a0080-616e-4eb3-b952-394914f09b65"> <id root="c827ef75-a2e9-4098-b606-5b3b1b38183f"/> <code code="34084-4" codeSystem="2.16.840.1.113883.6.1" displayName="ADVERSE REACTIONS SECTION"/> <title>6 ADVERSE REACTIONS </title> <text> <paragraph>The following clinically significant adverse reactions are also discussed elsewhere in the labeling:</paragraph> <list listType="unordered"> <item> <caption>•</caption>Serious Infections <content styleCode="italics">[see <linkHtml href="#ID_0622efa7-563c-4bd1-a678-012b3c491247">Warnings and Precautions (5.1)</linkHtml>]</content> </item> <item> <caption>•</caption>Hypersensitivity Reactions Including Anaphylaxis <content styleCode="italics">[see <linkHtml href="#ID_ac54e222-c42f-4bb9-ac2a-77059b3c7f5a">Warnings and Precautions (5.2)</linkHtml>]</content> </item> <item> <caption>•</caption>Malignancy <content styleCode="italics">[see <linkHtml href="#ID_a43e910e-e90a-496b-841d-fa189746063e">Warnings and Precautions (5.3)</linkHtml>]</content> </item> </list> </text> <effectiveTime value="20260424"/> <excerpt> <highlight> <text> <paragraph>Most common adverse drug reactions (incidence ≥5%) are nasopharyngitis, upper respiratory tract infections, bronchitis, infusion related reactions, herpes zoster and cough. (<linkHtml href="#ID_e08a0080-616e-4eb3-b952-394914f09b65">6</linkHtml>)</paragraph> <paragraph> <content styleCode="bold">To report SUSPECTED ADVERSE REACTIONS, contact </content> <content styleCode="bold">AstraZeneca at 1-800-236-9933</content> <content styleCode="bold"> or FDA at 1-800-FDA-1088 or <linkHtml href="http://www.fda.gov/medwatch">www.fda.gov/medwatch.</linkHtml> </content> </paragraph> </text> </highlight> </excerpt> <component> <section ID="ID_ff61362d-6225-41fa-a1c4-05d3c488f884"> <id root="a09ea7c0-941a-482d-8929-aceaceeeb1c1"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>6.1 Clinical Trials Experience </title> <text> <paragraph>Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.</paragraph> <paragraph> <content styleCode="underline">Adverse Reactions with Intravenous Administration</content> </paragraph> <paragraph>The safety of SAPHNELO was assessed in adult patients with moderate to severe SLE who received SAPHNELO 300 mg by intravenous infusion every 4 weeks (N=459) for 52 weeks, compared to placebo (N=466) in controlled clinical trials (Trials 1, 2 and 3) [see <content styleCode="italics"> <linkHtml href="#ID_3077249f-911e-46b6-8cea-64f8c1c3ec22">Clinical Studies (14.1)</linkHtml> </content>]. The population studied had a mean age of 41 years (range: 18 to 69), of which 93% were female, 60% White, 13% Black/African American, and 10% Asian.</paragraph> <paragraph>In the controlled-clinical trials, adverse reactions, irrespective of causality, were reported in 87% of patients receiving SAPHNELO and 79% of patients receiving placebo. </paragraph> <paragraph>Adverse reactions that occurred at greater than or equal to 2% incidence are shown in Table 1.</paragraph> <table width="100%"> <caption>Table 1 Adverse Reactions Occurring in ≥2% of Adults with Moderate to Severe SLE Treated with Intravenous SAPHNELO for 52 weeks in Trials 1, 2 and 3</caption> <col width="33%"/> <col width="33%"/> <col width="33%"/> <tbody> <tr> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Adverse Reaction</content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">SAPHNELO</content> </paragraph> <paragraph> <content styleCode="bold">(N=459)</content> </paragraph> <paragraph> <content styleCode="bold">%</content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Placebo</content> </paragraph> <paragraph> <content styleCode="bold">(N=466)</content> </paragraph> <paragraph> <content styleCode="bold">%</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph> Upper respiratory tract infection<footnote ID="_Ref43384025">Upper respiratory tract infections (including Upper respiratory tract infections, Nasopharyngitis, Pharyngitis)</footnote> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>34</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>23</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> Bronchitis<footnote ID="_Ref43384040">Bronchitis (including Bronchitis, Bronchitis viral, Tracheobronchitis)</footnote> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>11</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>5.2</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> Infusion‑related reactions</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>9.4</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>7.1</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> Herpes Zoster</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>6.1</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>1.3</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> Cough</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>5.0</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>3.2</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> Respiratory tract infection<footnote ID="_Ref43384063">Respiratory tract infection (including Respiratory tract infection, Respiratory tract infection viral, Respiratory tract infection bacterial)</footnote> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>3.3</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>1.5</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> Hypersensitivity</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>2.8</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>0.6</paragraph> </td> </tr> <tr> <td colspan="3" valign="top"> <paragraph>All patients received standard therapy.</paragraph> </td> </tr> </tbody> </table> <paragraph> <content styleCode="italics">Long-term Safety</content> </paragraph> <paragraph>Patients who completed Trials 2 and 3 (Phase III feeder trials) were eligible to continue on treatment in a randomized, double-blind, placebo-controlled long-term extension (LTE) trial, for an additional 3 years. The long-term safety of SAPHNELO was assessed in 257 patients who received SAPHNELO 300 mg every 4 weeks and 112 patients who received placebo in both a feeder trial and the LTE. Of these, 177 patients who received SAPHNELO (68.9%) and 52 patients who received placebo (46.4%) completed a total of 4 years on treatment. The overall long-term safety profile of SAPHNELO was consistent with Trials 1, 2 and 3.</paragraph> <paragraph> <content styleCode="italics">Specific Adverse Reactions</content> </paragraph> <paragraph> <content styleCode="italics">Infections: </content>In the 52‑week controlled-clinical trials, infections were reported in a greater proportion of patients while on treatment with SAPHNELO compared to placebo (69.7% versus 55.4%, respectively).</paragraph> <paragraph> <content styleCode="italics">Herpes Zoster: </content>In the 52‑week controlled-clinical trials, the incidence of herpes zoster in patients while on treatment with SAPHNELO was 6.1% and 1.3% in patients on placebo. Cases with multidermatomal involvement and disseminated presentation have been reported. Of the 28 SAPHNELO-treated patients with herpes zoster, 2 experienced disseminated disease requiring hospitalization compared to none among placebo-treated patients.</paragraph> <paragraph> <content styleCode="italics">Hypersensitivity Reactions Including Anaphylaxis:</content> During the SLE intravenous development program, there was one report of an anaphylactic reaction in a patient who received SAPHNELO 150 mg, and 4 reports of angioedema after 300 mg. In general, the hypersensitivity reactions were predominantly mild or moderate in intensity and did not lead to discontinuation of SAPHNELO.</paragraph> <paragraph>In the 52‑week controlled‑clinical trials, hypersensitivity reactions occurred in 2.8% of patients while on treatment with SAPHNELO and 0.6% of patients on placebo. Serious hypersensitivity reactions were reported in 0.6% of patients receiving SAPHNELO, including angioedema (n=2).</paragraph> <paragraph> <content styleCode="italics">Infusion‑related Reactions: </content>Infusion‑related reactions were mild to moderate in intensity; the most common symptoms were headache, nausea, vomiting, fatigue, and dizziness.</paragraph> <paragraph>In the 52‑week controlled‑clinical trials, the incidence of infusion‑related reactions while on treatment was 9.4% in patients while on treatment with SAPHNELO and 7.1% in patients on placebo.</paragraph> <paragraph> <content styleCode="italics">Malignancies: </content>In 52‑week controlled-clinical trials, malignancies (excluding non‑melanoma skin cancers) were observed in 0.7% and 0.6% of SAPHNELO-treated and placebo-treated patients. Malignant neoplasm (including non‑melanoma skin cancers) was reported in 1.3% of SAPHNELO-treated patients, compared to 0.6% placebo-treated patients. The malignancies that were reported in more than one patient treated with SAPHNELO included breast cancer and squamous cell carcinoma.</paragraph> <paragraph> <content styleCode="underline">Adverse Reactions with Subcutaneous Administration</content> </paragraph> <paragraph>The safety profile of SAPHNELO administered subcutaneously in adult patients with moderate to severe SLE is derived from Trial 5 <content styleCode="italics">[see <linkHtml href="#ID_77d1d46d-b690-4eaf-b40d-c20c8cc7537e">Clinical Studies (14.2)</linkHtml>]</content>. The data reflect SAPHNELO exposure in 185 patients who received SAPHNELO 120 mg by subcutaneous injection once every week, with a median duration of 52 weeks, as compared with comparable exposure to placebo in 182 patients. All patients received standard therapy. The population studied had a mean age of 43 years (range: 18 to 70), of which 92% were female, 74% White, 9% Asian, 8% American Indian or Alaska Native, and 5% Black/African American.</paragraph> <paragraph>The safety profile observed for SAPHNELO administered subcutaneously was consistent with the known safety profile of SAPHNELO administered intravenously<content styleCode="italics">.</content> </paragraph> <paragraph> <content styleCode="underline">Serious Infections in the Pool of Intravenous and Subcutaneous Trials</content> </paragraph> <paragraph>In the pool of four placebo-controlled clinical trials in adults with moderate to severe SLE where SAPHNELO was administered either intravenously or subcutaneously (Trials 1, 2, 3, and 5), the incidence of serious infections while on treatment was 5.4% in patients treated with SAPHNELO compared to 4.9% in patients receiving placebo. Fatal infections occurred while on treatment in 0.5% of SAPHNELO-treated patients and 0% in placebo-treated patients. The most frequent serious infection reported in patients treated with SAPHNELO was pneumonia. During the LTE of Trials 2 and 3, the most common serious infections were COVID‑19 and pneumonia.</paragraph> </text> <effectiveTime value="20260424"/> </section> </component> <component> <section ID="ID_8084456d-d289-4a11-ba71-70e75b9820dd"> <id root="8921765a-22b4-4e1c-8e3f-f72c91097f01"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>6.2 Postmarketing Experience </title> <text> <paragraph>The following adverse reaction has been identified during post-approval use of SAPHNELO. Because the reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.</paragraph> <paragraph>Arthralgia</paragraph> </text> <effectiveTime value="20240807"/> </section> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_adc0324b-a590-4b3b-a362-c107c1b3f7ca"> <id root="cb25a556-a6ef-4b80-9274-b4c85df1038f"/> <code code="34073-7" codeSystem="2.16.840.1.113883.6.1" displayName="DRUG INTERACTIONS SECTION"/> <title>7 DRUG INTERACTIONS </title> <text> <paragraph>No formal drug interaction trials have been conducted.</paragraph> </text> <effectiveTime value="20260424"/> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_48c03ccd-61ae-4094-a9e8-10cbcc5dc7a0"> <id root="bc11a597-fd28-4f02-9ec6-9b7c52f8fd1c"/> <code code="43684-0" codeSystem="2.16.840.1.113883.6.1" displayName="USE IN SPECIFIC POPULATIONS SECTION"/> <title>8 USE IN SPECIFIC POPULATIONS </title> <effectiveTime value="20260424"/> <component> <section ID="ID_14f23db1-eb47-44d5-b681-daed7d14b89c"> <id root="b4090de4-0b99-4327-b9d2-ba8806347bcd"/> <code code="42228-7" codeSystem="2.16.840.1.113883.6.1" displayName="PREGNANCY SECTION"/> <title>8.1 Pregnancy </title> <text> <paragraph> <content styleCode="underline">Pregnancy Exposure Registry</content> </paragraph> <paragraph>There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to SAPHNELO during pregnancy. For more information about the registry or to report a pregnancy while on SAPHNELO, healthcare providers should contact AstraZeneca at 1‑877‑693‑9268 or <linkHtml href="https://anifrolumabpregnancyandbreastfeedingstudy.us/">https://anifrolumabpregnancyandbreastfeedingstudy.us/</linkHtml>.</paragraph> <paragraph> <content styleCode="underline">Risk Summary</content> </paragraph> <paragraph>The limited human data with SAPHNELO use in pregnant women are insufficient to inform on drug‑associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcome. Monoclonal IgG antibodies are known to be actively transported across the placenta as pregnancy progresses; therefore, anifrolumab‑fnia exposure to the fetus may be greater during the third trimester of pregnancy.</paragraph> <paragraph>In an enhanced pre- and post-natal development study with pregnant cynomolgus monkeys that received intravenous administration of anifrolumab-fnia, there was no evidence of embryotoxicity or fetal malformations with exposures up to approximately 28‑times the exposure at the maximum recommended human dose (MRHD) on an Area Under Curve (AUC) basis <content styleCode="italics">(see <linkHtml href="#_Data">Data</linkHtml>)</content>.</paragraph> <paragraph>All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.</paragraph> <paragraph> <content styleCode="underline">Clinical Considerations</content> </paragraph> <paragraph> <content styleCode="italics">Disease-Associated Maternal and/or Embryo/Fetal Risk</content>: Pregnant women with SLE are at increased risk of adverse pregnancy outcomes, including worsening of the underlying disease, premature birth, miscarriage, and intrauterine growth restriction. Maternal lupus nephritis increases the risk of hypertension and preeclampsia/eclampsia. Passage of maternal autoantibodies across the placenta may result in adverse neonatal outcomes, including neonatal lupus and congenital heart block.</paragraph> <paragraph ID="_Data"> <content styleCode="underline">Data</content> </paragraph> <paragraph> <content styleCode="italics">Animal Data</content>: In an enhanced pre- and post-natal development study, pregnant cynomolgus monkeys received anifrolumab-fnia at intravenous doses of 30 or 60 mg/kg once every 2 weeks from confirmation of pregnancy at Gestation Day 20, throughout the gestation period, and continuing until 1‑month post-partum (approximately Lactation Day 28). There was no evidence of anifrolumab-fnia related maternal toxicity, embryo-fetal toxicity, or post-natal developmental effects. No anifrolumab-fnia related effect on T-cell-dependent antibody response in the infants was noted up to Day 180 after birth. The no observed adverse effect level (NOAEL) for maternal and developmental toxicity was identified as 60 mg/kg (approximately 28‑times the MRHD on an AUC basis). In the infants, mean serum concentrations of anifrolumab‑fnia on Day 30 after birth increased with dose and were approximately 4.2% to 9.7% of the respective maternal concentrations. The anifrolumab-fnia concentrations in the infant serum were up to approximately 22‑times the concentrations in the maternal milk, suggesting that anifrolumab-fnia had transferred via the placenta.</paragraph> </text> <effectiveTime value="20260424"/> </section> </component> <component> <section ID="ID_f12f634b-67fd-416f-b4bf-49fd1020a094"> <id root="538eb055-edb4-446b-81a1-d5bc66c3faf4"/> <code code="77290-5" codeSystem="2.16.840.1.113883.6.1" displayName="LACTATION SECTION"/> <title>8.2 Lactation </title> <text> <paragraph> <content styleCode="underline">Risk Summary</content> </paragraph> <paragraph>No data are available regarding the presence of SAPHNELO in human milk, the effects on the breastfed child, or the effects on milk production. Anifrolumab-fnia was detected in the milk of female cynomolgus monkeys administered anifrolumab-fnia. Due to species-species differences in lactation physiology, animal data may not reliably predict drug levels in humans. Maternal IgG is known to be present in human milk. If anifrolumab-fnia is transferred into human milk, the effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to anifrolumab-fnia are unknown.</paragraph> <paragraph>The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for SAPHNELO and any potential adverse effects on the breast-fed child from SAPHNELO or from the underlying maternal condition.</paragraph> </text> <effectiveTime value="20260424"/> </section> </component> <component> <section ID="ID_70327d32-6dfe-4d47-9a06-5100bb925cc6"> <id root="aa6dc68b-0b41-49b8-a33c-0ac60eef8d06"/> <code code="34081-0" codeSystem="2.16.840.1.113883.6.1" displayName="PEDIATRIC USE SECTION"/> <title>8.4 Pediatric Use </title> <text> <paragraph>The safety and efficacy of SAPHNELO in pediatric patients have not been established.</paragraph> </text> <effectiveTime value="20260424"/> </section> </component> <component> <section ID="ID_a897bd37-c861-4ce6-84e4-136ede159b32"> <id root="bc19bcab-ec86-4bbc-a76c-4e90a3c4f8f5"/> <code code="34082-8" codeSystem="2.16.840.1.113883.6.1" displayName="GERIATRIC USE SECTION"/> <title>8.5 Geriatric Use </title> <text> <paragraph>Of the 952 patients with moderate to severe SLE exposed to SAPHNELO in clinical trials, 3% (n=33) were 65 and over. The number of patients aged 65 years of age and older was not sufficient to determine whether they respond differently from younger adult patients.</paragraph> </text> <effectiveTime value="20260424"/> </section> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_afb06fdc-a5ce-4ce2-8658-1a4bc3724190"> <id root="55f13598-a8eb-48b5-a6f4-20ce8ab56fa2"/> <code code="34089-3" codeSystem="2.16.840.1.113883.6.1" displayName="DESCRIPTION SECTION"/> <title>11 DESCRIPTION </title> <text> <paragraph>Anifrolumab-fnia is a type I interferon (IFN) receptor antagonist, immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that is produced in mouse myeloma cells (NS0) by recombinant DNA technology. The molecular weight is approximately 148 kDa.</paragraph> <paragraph> <content styleCode="underline">Intravenous Infusion</content> </paragraph> <paragraph>SAPHNELO (anifrolumab-fnia) injection is a sterile, preservative‑free, clear to opalescent, colorless to slightly yellow, solution in a single-dose vial for intravenous use. </paragraph> <paragraph>Each 2 mL single-dose vial contains 300 mg (150 mg/mL) of anifrolumab-fnia, L-histidine (3 mg), L-histidine hydrochloride monohydrate (6 mg), L-lysine hydrochloride (18 mg), polysorbate 80 (1 mg), trehalose dihydrate (98 mg), and Water for Injection, USP. The pH is 5.9.</paragraph> <paragraph> <content styleCode="underline">Subcutaneous Injection</content> </paragraph> <paragraph>SAPHNELO (anifrolumab-fnia) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow, solution in a prefilled syringe or autoinjector for subcutaneous injection.</paragraph> <paragraph>Each 0.8 mL single-dose prefilled syringe or autoinjector delivers 120 mg of anifrolumab-fnia, histidine (1 mg), L-histidine hydrochloride monohydrate (3 mg), lysine hydrochloride (7 mg), polysorbate 80 (0.4 mg), trehalose (36 mg), and Water for Injection, USP. The pH is 5.9.</paragraph> </text> <effectiveTime value="20260424"/> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_9d26338d-743f-41f6-9110-305d7411fe2a"> <id root="97fa2d78-507a-4f90-b352-be5a740b0ecc"/> <code code="34090-1" codeSystem="2.16.840.1.113883.6.1" displayName="CLINICAL PHARMACOLOGY SECTION"/> <title>12 CLINICAL PHARMACOLOGY </title> <effectiveTime value="20260424"/> <component> <section ID="ID_5d08e8de-e4b9-48f4-a8da-3f4478626d76"> <id root="f37e155f-1fe0-4c97-98f3-9aa3b12f21d7"/> <code code="43679-0" codeSystem="2.16.840.1.113883.6.1" displayName="MECHANISM OF ACTION SECTION"/> <title>12.1 Mechanism of Action </title> <text> <paragraph>Anifrolumab-fnia is a human IgG1κ monoclonal antibody that binds to subunit 1 of the type I interferon receptor (IFNAR) with high specificity and affinity. This binding inhibits type I IFN signaling, thereby blocking the biologic activity of type I IFNs. Anifrolumab-fnia also induces the internalization of IFNAR1, thereby reducing the levels of cell surface IFNAR1 available for receptor assembly. Blockade of receptor mediated type I IFN signaling inhibits IFN responsive gene expression as well as downstream inflammatory and immunological processes. Inhibition of type I IFN blocks plasma cell differentiation and normalizes peripheral T-cell subsets.</paragraph> <paragraph>Type I IFNs play a role in the pathogenesis of SLE. Approximately 60-80% of adult patients with active SLE express elevated levels of type I IFN inducible genes.</paragraph> </text> <effectiveTime value="20260424"/> </section> </component> <component> <section ID="ID_d599cad0-973d-48be-b733-3825bfedf466"> <id root="686cca3a-a86e-448d-aa2c-0aec23a734ef"/> <code code="43681-6" codeSystem="2.16.840.1.113883.6.1" displayName="PHARMACODYNAMICS SECTION"/> <title>12.2 Pharmacodynamics </title> <text> <paragraph>In patients with moderate to severe SLE, following the administration of SAPHNELO, neutralization (≥80%) of a type I IFN gene signature was observed from Week 4 to Week 52 in blood samples of patients with elevated levels of type I IFN inducible genes and returned to baseline levels within 8 to 12 weeks following withdrawal of SAPHNELO at the end of the 52‑week treatment period. However, the clinical relevance of the type I IFN gene signature neutralization is unclear.</paragraph> <paragraph>In SLE patients with positive anti-dsDNA antibodies at baseline (Trials 2 and 3), treatment with SAPHNELO led to numerical reductions in anti-dsDNA antibodies over time through Week 52.</paragraph> <paragraph>In patients with low complement levels (C3 and C4) at baseline (Trials 2 and 3), increases in complement levels were observed in patients receiving SAPHNELO through Week 52.</paragraph> </text> <effectiveTime value="20260424"/> </section> </component> <component> <section ID="ID_af451972-036a-4dd1-8970-2753a60c4cd2"> <id root="128e8276-22ab-465f-b288-fb3c8120f760"/> <code code="43682-4" codeSystem="2.16.840.1.113883.6.1" displayName="PHARMACOKINETICS SECTION"/> <title>12.3 Pharmacokinetics </title> <text> <paragraph>The pharmacokinetics (PK) of anifrolumab-fnia was studied in adult patients with SLE following intravenous doses ranging from one-third (100 mg) to 3.3 times (1000 mg) the approved intravenous dosage, 300 mg once every 4 weeks, and subcutaneous 120 mg weekly doses, as well as in healthy volunteers following a single intravenous dose at 300 mg and a single subcutaneous dose of 120 mg. </paragraph> <paragraph>Anifrolumab-fnia exhibits non-linear PK in the dose range of 100 mg to 1000 mg with more than dose-proportional increases in the exposure as measured by AUC, following intravenous administration.</paragraph> <paragraph>The estimated time to reach steady state is approximately 112 days for both intravenous and subcutaneous administration.</paragraph> <paragraph>Following 300 mg intravenous administrations every 4 weeks, the accumulation ratio for C<sub>max</sub> was 1.11 and for C<sub>trough</sub> was 2.37. Following 120 mg subcutaneous administration weekly, the accumulation ratio for C<sub>max</sub> was 1.85 and C<sub>trough</sub> was 1.85.</paragraph> <paragraph> <content styleCode="underline">Absorption</content> </paragraph> <paragraph>The bioavailability of anifrolumab-fnia was estimated to be 73% following subcutaneous injection. The estimated maximum serum concentration (C<sub>max</sub>) of anifrolumab-fnia at steady state was 63.7 μg/mL.</paragraph> <paragraph> <content styleCode="underline">Distribution</content> </paragraph> <paragraph>Based on population PK analysis, the estimated volume of distribution at steady state for a typical patient with SLE (68 kg) is 5.16 L.</paragraph> <paragraph> <content styleCode="underline">Elimination</content> </paragraph> <paragraph>From population PK analysis, anifrolumab-fnia exhibited non-linear PK due to IFNAR1-mediated drug clearance.</paragraph> <paragraph>The estimated systemic clearance (CL) for anifrolumab-fnia is 0.146 L/day.</paragraph> <paragraph>Based on population PK analysis of patients who received SAPHNELO for one year, serum concentrations of anifrolumab-fnia were below detection in 95% of patients approximately 16 weeks after the last dose.</paragraph> <paragraph> <content styleCode="underline">Specific Populations</content> </paragraph> <paragraph>There was no clinically meaningful difference in systemic clearance based on age, race, ethnicity, region, gender, IFN status or body weight, that requires dose adjustment.</paragraph> <paragraph> <content styleCode="italics">Age:</content> Based on population PK analyses, age (range 18 to 70 years) did not affect anifrolumab-fnia clearance. Limited PK data are available for geriatric patients; 3% (n=33) of the patients included in the PK analysis were 65 years or older <content styleCode="italics">[see <linkHtml href="#ID_a897bd37-c861-4ce6-84e4-136ede159b32">Use in Specific Populations (8.5)</linkHtml>]</content>.</paragraph> <paragraph> <content styleCode="italics">Patients with Renal Impairment:</content> No specific clinical trials have been conducted to investigate the effect of renal impairment on anifrolumab-fnia. Based on population PK analyses, anifrolumab-fnia clearance was comparable in SLE patients with mild (60-89 mL/min/1.73 m<sup>2</sup>) and moderate (30-59 mL/min/1.73 m<sup>2</sup>) decrease in eGFR values and patients with normal renal function (≥90 mL/min/1.73 m<sup>2</sup>). There were no SLE patients with a severe decrease in eGFR or end stage renal disease (<30 mL/min/1.73 m<sup>2</sup>); anifrolumab-fnia is not cleared renally.</paragraph> <paragraph>Patients with urine protein/creatinine ratio (UPCR) >2 mg/mg were excluded from the clinical trials. Based on population PK analyses, increased UPCR did not significantly affect anifrolumab-fnia clearance.</paragraph> <paragraph> <content styleCode="italics">Patients with Hepatic Impairment:</content> No specific clinical trials have been conducted to investigate the effect of hepatic impairment on anifrolumab-fnia. IgG1 monoclonal antibodies are predominantly eliminated via catabolism and are not expected to undergo hepatic metabolism; changes in hepatic function are not expected to influence anifrolumab-fnia clearance. Based on population PK analyses, baseline hepatic function biomarkers (ALT and AST ≤2.0 × ULN, and total bilirubin) had no clinically relevant effect on anifrolumab-fnia clearance.</paragraph> <paragraph> <content styleCode="underline">Drug Interactions</content> </paragraph> <paragraph>No formal drug-drug interaction trials have been conducted.</paragraph> <paragraph>Based on population PK analysis, concomitant use of oral corticosteroids, anti-malarials, immunosuppressants (azathioprine, methotrexate, mycophenolate mofetil, mycophenolic acid, and mizoribine), NSAIDs, ACE inhibitors, and HMG-CoA reductase inhibitors did not significantly affect the PK of anifrolumab-fnia.</paragraph> </text> <effectiveTime value="20260424"/> </section> </component> <component> <section ID="ID_64098e34-414f-4502-bc88-cbfbf175ed5b"> <id root="eef43cf8-e053-4bde-aa20-62a315f97191"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>12.6 Immunogenicity </title> <text> <paragraph>The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies (ADA) in the trials described below with the incidence of anti-drug antibodies in other trials, including those of anifrolumab-fnia.</paragraph> <paragraph>In Trials 2, 3, and the long-term extension trial, treatment emergent anti-anifrolumab-fnia antibodies were detected in 9 of 350 patients (ADA incidence 2.6%) who received SAPHNELO at the recommended intravenous dosing regimen for up to 4 years. </paragraph> <paragraph>In Trial 5, treatment emergent anti-anifrolumab-fnia antibodies were detected in 6 of 107 patients (ADA incidence 5.6%) treated with SAPHNELO at the recommended subcutaneous dosing regimen during the 52‑week treatment period. No neutralizing antibodies were detected.</paragraph> <paragraph>Because of the low occurrence of anti-drug antibodies, the effect of these antibodies on the pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of anifrolumab-fnia products is unknown.</paragraph> </text> <effectiveTime value="20260424"/> </section> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_caeebfb5-a4c4-4daf-a645-de3e82dd8cca"> <id root="c091c364-a661-470a-9623-1cf75353cc02"/> <code code="43680-8" codeSystem="2.16.840.1.113883.6.1" displayName="NONCLINICAL TOXICOLOGY SECTION"/> <title>13 NONCLINICAL TOXICOLOGY </title> <effectiveTime value="20260424"/> <component> <section ID="ID_9497c6fb-7098-405c-81ab-531e4ae36280"> <id root="96c6f2a0-7f34-4dbd-bd5f-6db71fda97ca"/> <code code="34083-6" codeSystem="2.16.840.1.113883.6.1" displayName="CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION"/> <title>13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility </title> <text> <paragraph>The carcinogenic and genotoxic potential of anifrolumab-fnia have not been evaluated. In rodent models of IFNAR1 blockade, increased carcinogenic potential has been observed. The clinical relevance of these findings is unknown.</paragraph> <paragraph>Effects on male and female fertility have not been directly evaluated in animal studies. No anifrolumab-fnia-related adverse effects on indirect measures of male or female fertility, based on semen analysis, spermatogenesis staging, menses cycle, organ weights and histopathological findings in the reproductive organs were observed in 9-month repeat-dose toxicity studies in cynomolgus monkeys at doses up to 50 mg/kg intravenous once weekly (approximately 58‑times the MRHD on an AUC basis) and 60 mg/kg subcutaneous once weekly (approximately 52-times the subcutaneous MRHD on an AUC basis).</paragraph> </text> <effectiveTime value="20260424"/> </section> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_60cc6a88-5e8e-4e59-bcfa-19512651bcf3"> <id root="bd383210-6526-4a02-80f7-371290e99a6e"/> <code code="34092-7" codeSystem="2.16.840.1.113883.6.1" displayName="CLINICAL STUDIES SECTION"/> <title>14 CLINICAL STUDIES </title> <effectiveTime value="20260424"/> <component> <section ID="ID_3077249f-911e-46b6-8cea-64f8c1c3ec22"> <id root="5f08e300-03e0-4d4b-a688-27758bbc145e"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>14.1 Intravenous Administration in Adults with Moderate to Severe SLE </title> <text> <paragraph> <content styleCode="underline">Trial Design and Population</content> </paragraph> <paragraph>The safety and efficacy of SAPHNELO were evaluated in three 52-week treatment period, multicenter, randomized, double-blind, placebo-controlled trials (Trial 1 [NCT01438489], Trial 2 [NCT02446912] and Trial 3 [NCT02446899]). Patients were diagnosed with SLE according to the American College of Rheumatology (1982 revised) classification criteria. All patients were ≥18 years of age and had moderate to severe disease, with a SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥6 points, organ level involvement based on the British Isles Lupus Assessment Group (BILAG) assessment, and a Physician’s Global Assessment [PGA] score ≥1, despite receiving standard SLE therapy consisting of either one or any combination of oral corticosteroids (OCS), antimalarials and/or immunosuppressants at baseline. Patients continued to receive their existing SLE therapy at stable doses during the clinical trials, with the exception of OCS (prednisone or equivalent) where tapering was a component of the protocol. Patients who had severe active lupus nephritis and patients who had severe active central nervous system lupus were excluded. The use of other biologic agents and cyclophosphamide were not permitted during the trials; patients receiving other biologic therapies were required to complete a wash-out period of at least 5 half‑lives prior to enrollment. All three trials were conducted in North America, Europe, South America and Asia. Patients received SAPHNELO or placebo, administered by intravenous infusion, every 4 weeks.</paragraph> <paragraph>Efficacy of SAPHNELO was established based on assessment of clinical response using the composite endpoints, the British Isles Lupus Assessment Group based Composite Lupus Assessment (BICLA) and the SLE Responder Index (SRI‑4).</paragraph> <paragraph>BICLA response at Week 52, was defined as improvement in all organ domains with moderate or severe activity at baseline:</paragraph> <list listType="unordered"> <item> <caption>•</caption>Reduction of all baseline BILAG A to B/C/D and baseline BILAG B to C/D, and no BILAG worsening in other organ systems, as defined by ≥1 new BILAG A or ≥2 new BILAG B;</item> <item> <caption>•</caption>No worsening from baseline in SLEDAI-2K, where worsening is defined as an increase from baseline of >0 points in SLEDAI-2K;</item> <item> <caption>•</caption>No worsening from baseline in patients’ lupus disease activity, where worsening is defined by an increase ≥0.30 points on a 3-point PGA visual analogue scale (VAS);</item> <item> <caption>•</caption>No discontinuation of treatment;</item> <item> <caption>•</caption>No use of restricted medication beyond the protocol-allowed threshold.</item> </list> <paragraph>SRI‑4 response, was defined as meeting each of the following criteria at Week 52 compared with baseline:</paragraph> <list listType="unordered"> <item> <caption>•</caption>Reduction from baseline of ≥4 points in the SLEDAI-2K;</item> <item> <caption>•</caption>No new organ system affected as defined by 1 or more BILAG A or 2 or more BILAG B items compared to baseline;</item> <item> <caption>•</caption>No worsening from baseline in the patients’ lupus disease activity defined by an increase ≥0.30 points on a 3‑point PGA VAS;</item> <item> <caption>•</caption>No discontinuation of treatment;</item> <item> <caption>•</caption>No use of restricted medication beyond the protocol-allowed threshold.</item> </list> <paragraph>Trial 1 randomized 305 patients (1:1:1) who received SAPHNELO, 300 mg or 1000 mg, or placebo once every 4 weeks for up to 52 weeks. The primary endpoint was a combined assessment of the SRI-4 and the sustained reduction in OCS (<10 mg/day and ≤OCS dose at Week 1, sustained for 12 weeks) measured at Week 24.</paragraph> <paragraph>Trial 2 and 3 were similar in design. Trial 2 randomized 457 patients (1:2:2) who received SAPHNELO 150 mg, 300 mg once every 4 weeks or placebo. Trial 3 randomized 362 patients (1:1) who received SAPHNELO 300 mg once every 4 weeks or placebo. The primary endpoints were improvement in disease activity evaluated at 52 weeks, measured by SRI‑4 in Trial 2 and BICLA in Trial 3 (defined above). The common secondary efficacy endpoints included in both trials were the maintenance of OCS reduction, improvement in cutaneous SLE activity, and flare rate. During Weeks 8-40, patients with a baseline OCS ≥10 mg/day were required to taper their OCS dose to ≤7.5 mg/day, unless there was worsening of disease activity. Both trials evaluated the efficacy of SAPHNELO 300 mg once every 4 weeks versus placebo; a dose of 150 mg was also evaluated for dose-response in Trial 2.</paragraph> <paragraph>Patient demographics and disease characteristics were generally similar and balanced across treatment arms (Table 2).</paragraph> <table styleCode="Noautorules" width="100%"> <caption>Table 2 Demographics and Baseline Characteristics of Adults with Moderate to Severe SLE in Trials 1, 2, and 3</caption> <col width="32%"/> <col width="18%"/> <col width="25%"/> <col width="25%"/> <tbody> <tr> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"/> <td align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="middle"> <paragraph> <content styleCode="bold">Total Population</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"/> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph> <content styleCode="bold">Trial 1</content> </paragraph> <paragraph> <content styleCode="bold">(N=305)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph> <content styleCode="bold">Trial 2</content> </paragraph> <paragraph> <content styleCode="bold">(N=457)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph> <content styleCode="bold">Trial 3</content> </paragraph> <paragraph> <content styleCode="bold">(N=362)</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Mean Age (years)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>40</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>41</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>42</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Female (%)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>93</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>92</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>93</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">White (%)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>42</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>71</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>60</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Black/African American (%)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>13</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>14</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>12</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Asian (%)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>7</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>5</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>17</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Hispanic or Latino (%)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>42</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>19</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>30</paragraph> </td> </tr> <tr> <td colspan="4" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Baseline SLEDAI-2K score</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> Mean (SD)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>10.9 (4.1)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>11.3 (3.72)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>11.5 (3.76)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> ≥10 points, n (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>182 (60)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>328 (72)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>260 (72)</paragraph> </td> </tr> <tr> <td colspan="4" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">BILAG organ system scoring (Overall)</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> At least one A, n (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>152 (50)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>217 (48)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>176 (49)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> No A and at least 2 Bs, n (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>134 (44)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>211 (46)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>169 (47)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Positive Anti-dsDNA levels, n (%)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>185 (77)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>207 (45)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>159 (44)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Abnormal ANA, n (%)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>299 (98)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>412 (90)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>325 (90)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Abnormal Complement C3 level, n (%)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>119 (39)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>157 (34)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>144 (40)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Abnormal Complement C4 level, n (%)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>74 (24)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>95 (21)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>95 (26)</paragraph> </td> </tr> <tr> <td colspan="4" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Baseline SLE treatment</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> OCS, n (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>258 (85)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>381 (83)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>292 (81)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> Antimalarials, n (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>219 (72)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>334 (73)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>252 (70)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> Immunosuppressants, n (%)</paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"> <paragraph>150 (49)</paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"> <paragraph>214 (47)</paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="middle"> <paragraph>174 (48)</paragraph> </td> </tr> </tbody> </table> <paragraph>Randomization was stratified by disease severity (SLEDAI-2K score at baseline, <10 vs ≥10 points), OCS dose on Day 1 (<10 mg/day vs ≥10 mg/day prednisone or equivalent) and interferon gene signature test results (high vs low).</paragraph> <paragraph> <content styleCode="underline">Trials 1, 2, and 3 Results</content> </paragraph> <paragraph>Although other intravenous SAPHNELO dosages were studied in Trials 1 and 2, only data for the approved intravenous SAPHNELO dosage of 300 mg every 4 weeks are presented below.</paragraph> <paragraph>The reduction in disease activity seen in the BICLA and SRI-4 was related primarily to improvement in the mucocutaneous and musculoskeletal organ systems. Flare rate was reduced in SAPHNELO patients compared to placebo patients although the difference was not statistically significant.</paragraph> <paragraph> <content styleCode="italics">BICLA</content> <content styleCode="italics">responder analysis</content> </paragraph> <paragraph>BICLA was the primary endpoint in Trial 3, SAPHNELO 300 mg once every 4 weeks demonstrated statistically significant and clinically meaningful efficacy in overall disease activity compared with placebo, with greater improvements in all components of the composite endpoint. In Trial 1 and 2, BICLA was a pre-specified analysis. The BICLA results are presented in Table 3.</paragraph> <table width="100%"> <caption>Table 3 BICLA Response Rate at Week 52 in Adults with Moderate to Severe SLE in Trials 1, 2, and 3</caption> <col width="20%"/> <col width="14%"/> <col width="13%"/> <col width="14%"/> <col width="12%"/> <col width="14%"/> <col width="14%"/> <tbody> <tr> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"/> <td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"> <paragraph> <content styleCode="bold">Trial 1</content> <footnote ID="_Ref184127397">Not formally tested in a pre-specified testing scheme and findings should be interpreted with caution.</footnote> <footnote ID="_Ref184127481">Based on post hoc analysis. </footnote> </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"> <paragraph> <content styleCode="bold">Trial 2</content> <footnoteRef IDREF="_Ref184127397"/> <footnoteRef IDREF="_Ref184127481"/> </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"> <paragraph> <content styleCode="bold">Trial 3</content> <footnote ID="_Ref184127524">Primary endpoint.</footnote> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"/> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph> <content styleCode="bold">SAPHNELO 300 mg once every 4 weeks</content> </paragraph> <paragraph> <content styleCode="bold">(N=99)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph> <content styleCode="bold">Placebo</content> </paragraph> <paragraph> <content styleCode="bold">(N=102)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph> <content styleCode="bold">SAPHNELO 300 mg once every 4 weeks</content> </paragraph> <paragraph> <content styleCode="bold"> (N=180)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph> <content styleCode="bold">Placebo</content> </paragraph> <paragraph> <content styleCode="bold">(N=184)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph> <content styleCode="bold">SAPHNELO 300 mg once every 4 weeks</content> </paragraph> <paragraph> <content styleCode="bold"> (N=180)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph> <content styleCode="bold">Placebo</content> </paragraph> <paragraph> <content styleCode="bold">(N=182)</content> </paragraph> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph> <content styleCode="bold">BICLA Response Rate</content> <footnote ID="_Ref184127535">In all 3 trials, patients who discontinued investigational product or initiated restricted medications beyond the protocol-specified thresholds are considered non-responders. For consistency, the results presented for Trial 2 represent the post-hoc analysis using the restricted medication thresholds as defined in Trial 3.</footnote> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>Responder, n (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>54 (54.6)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>27 (25.8)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>85 (47.1)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>55 (30.2)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>86 (47.8)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>57 (31.5)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>Difference in Response Rates (95% CI)</paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>28.8 (15.7, 41.9)</paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>17.0 (7.2, 26.8)</paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>16.3 (6.3, 26.3)</paragraph> <paragraph>p-value=0.001</paragraph> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph> <content styleCode="bold">Components of BICLA Response</content> <footnoteRef IDREF="_Ref184127535"/> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>BILAG Improvement, n (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>54 (54.5)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>28 (27.5)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>85 (47.2)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>58 (31.5)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>88 (48.9)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>59 (32.4)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>No Worsening of SLEDAI-2K, n (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>73 (73.7)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>61 (59.8)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>121 (67.2)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>104 (56.5)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>122 (67.8)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>94 (51.6)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>No Worsening of PGA, n (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>76 (76.8)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>62 (60.8)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>117 (65.0)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>105 (57.1)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>122 (67.8)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>95 (52.2)</paragraph> </td> </tr> <tr> <td colspan="7" valign="top"> <paragraph>The response rates and associated difference and 95% CI are calculated using a Cochran-Mantel-Haenszel approach adjusted for stratification factors. The reported percentages for the components are unadjusted.</paragraph> </td> </tr> </tbody> </table> <paragraph>In Trial 3, examination of subgroups by age, race, gender, ethnicity, disease severity [SLEDAI-2K at baseline], and baseline OCS use did not identify differences in response to SAPHNELO.</paragraph> <paragraph>Figure 1 shows the proportion of BICLA responders through the 52-week treatment period in Trial 3.</paragraph> <paragraph> <content styleCode="bold">Figure 1 Trial 3: Proportion (%) of BICLA Responders in Adults with Moderate to Severe SLE by Visit*</content> </paragraph> <renderMultiMedia ID="id-797368265" referencedObject="CF646C93-944D-4E4A-9117-C92326AA8E7C"/> <paragraph> <content styleCode="italics">SRI-4 responder analysis</content> </paragraph> <paragraph>SRI-4 was the primary endpoint in Trial 2, treatment with SAPHNELO did not result in statistically significant improvements over placebo. In Trials 1 and 3, SRI-4 was a pre-specified analysis. The SRI-4 results are presented in Table 4.</paragraph> <table width="100%"> <caption>Table 4 SRI-4 Response Rate at Week 52 in Adults with Moderate to Severe SLE in Trials 1, 2, and 3</caption> <col width="22%"/> <col width="16%"/> <col width="12%"/> <col width="14%"/> <col width="11%"/> <col width="15%"/> <col width="11%"/> <tbody> <tr> <td rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"/> <td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"> <paragraph> <content styleCode="bold">Trial 1</content> <footnote ID="_Ref184138958">Not formally tested in a pre-specified testing scheme and findings should be interpreted with caution.</footnote> </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"> <paragraph> <content styleCode="bold">Trial 2</content> <footnote ID="_Ref184139018">Primary endpoint.</footnote> </paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"> <paragraph> <content styleCode="bold">Trial 3</content> <footnoteRef IDREF="_Ref184138958"/> </paragraph> </td> </tr> <tr> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph> <content styleCode="bold">SAPHNELO 300 mg once every 4 weeks (N=99)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph> <content styleCode="bold">Placebo</content> </paragraph> <paragraph> <content styleCode="bold">(N=102)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph> <content styleCode="bold">SAPHNELO 300 mg once every 4 weeks (N=180)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph> <content styleCode="bold">Placebo</content> </paragraph> <paragraph> <content styleCode="bold">(N=184)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph> <content styleCode="bold">SAPHNELO 300 mg once every 4 weeks (N=180)</content> </paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph> <content styleCode="bold">Placebo</content> </paragraph> <paragraph> <content styleCode="bold">(N=182)</content> </paragraph> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">SRI-4 Response Rate</content> <footnote ID="_Ref184139106">In all 3 trials, patients who discontinued investigational product or initiated restricted medications beyond the protocol-specified thresholds are considered non-responders. For consistency, the results presented for Trial 2 represent the post-hoc analysis using the restricted medication thresholds as defined in Trial 3. The most commonly involved SLEDAI-2K organ domains were mucocutaneous, musculoskeletal and immune.</footnote> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>Responder, n (%)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>62 (62.8)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>41 (38.8)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>88 (49.0)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>79 (43.0)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>100 (55.5)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>68 (37.3)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="middle"> <paragraph>Difference in Response Rates (95% CI)</paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>24.0 (10.9, 37.2)</paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>6.0 (-4.2, 16.2)</paragraph> </td> <td align="center" colspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <paragraph>18.2 (8.1, 28.3)</paragraph> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Components of SRI-4 Response</content> <footnoteRef IDREF="_Ref184139106"/> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>SLEDAI-2K improvement, n (%)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>62 (62.6)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>41 (40.2)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>89 (49.4)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>80 (43.5)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>101 (56.1)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>71 (39.0)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>No worsening of BILAG, n (%)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>75 (75.8)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>61 (59.8)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>119 (66.1)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>105 (57.1)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>125 (69.4)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>94 (51.6)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>No worsening of PGA, n (%)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>76 (76.8)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>62 (60.8)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>117 (65.0)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>105 (57.1)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>122 (67.8)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>95 (52.2)</paragraph> </td> </tr> <tr> <td colspan="7" valign="top"> <paragraph>The response rates and associated difference and 95% CI are calculated using a Cochran-Mantel-Haenszel approach adjusted for stratification factors. The reported percentages for the components are unadjusted.</paragraph> </td> </tr> </tbody> </table> <paragraph> <content styleCode="italics">Effect on Concomitant Steroid Treatment</content> </paragraph> <paragraph>In Trial 3, among the 47% of patients with a baseline OCS use ≥10 mg/day, SAPHNELO demonstrated a statistically significant difference in the proportion of patients able to reduce OCS use by at least 25% to ≤7.5 mg/day at Week 40 and maintain the reduction through Week 52 (p-value = 0.004); 52% (45/87) of patients in the SAPHNELO group versus 30% (25/83) in the placebo group achieved this level of steroid reduction (difference 21% [95% CI 6.8, 35.7]). Consistent trends in favor of SAPHNELO compared to placebo, on effect of reduction of OCS use, were observed in Trial 1 and 2, but the difference was not statistically significant.</paragraph> </text> <effectiveTime value="20260424"/> <component> <observationMedia ID="CF646C93-944D-4E4A-9117-C92326AA8E7C"> <text>figure_1</text> <value mediaType="image/jpeg"> <reference value="image-01.jpg"/> </value> </observationMedia> </component> </section> </component> <component> <section ID="ID_77d1d46d-b690-4eaf-b40d-c20c8cc7537e"> <id root="dae25aa6-8edd-4e4e-a211-e5acfe0fc428"/> <code code="42229-5" codeSystem="2.16.840.1.113883.6.1" displayName="SPL UNCLASSIFIED SECTION"/> <title>14.2 Subcutaneous Administration in Adults with Moderate to Severe SLE </title> <text> <paragraph>The safety and efficacy of SAPHNELO administered subcutaneously were evaluated in a 52-week treatment period, multicenter, randomized, double-blind, placebo-controlled trial (Trial 5 [NCT04877691]). All patients were ≥18 years of age, diagnosed with SLE according to the American College of Rheumatology (1997 revised) classification criteria, and had moderate to severe disease, with a SLEDAI-2K score ≥6 points, organ level involvement based on BILAG assessment, and a PGA score ≥1, despite receiving standard SLE therapy consisting of either one or any combination of OCS, antimalarials and/or immunosuppressants at baseline. Patients continued to receive their existing SLE therapy at stable doses during the trial, with the exception of OCS (prednisone or equivalent) where tapering was a component of the protocol. Patients who had severe active lupus nephritis or severe active central nervous system lupus were excluded. Patients were randomized (1:1) to receive SAPHNELO 120 mg plus standard therapy or placebo plus standard therapy by subcutaneous injection once every week. Randomization was stratified by SLEDAI‑2K score at baseline (<10 vs ≥10 points), OCS dose on Day 1 (<10 mg/day vs ≥10 mg/day prednisone or equivalent) and interferon gene signature test results (high vs low).</paragraph> <paragraph>A pre-specified interim analysis was conducted when the first 220 randomized patients completed Week 52 or had withdrawn from the trial. Of these, 89% were female, 45% Hispanic or Latino, 78% White, 7% American Indian or Alaska Native, 7% Asian, and 4% Black/African American. The mean age was 43 years. At baseline, the mean SLEDAI‑2K score was 10.9 (SD: 3.4) and 67% had high disease activity (SLEDAI‑2K score ≥10), 45% had severe disease (BILAG A) in at least 1 organ system and 50% had moderate disease (BILAG B) in at least 2 organ systems. The most commonly affected organ systems (BILAG A or B at baseline) were the musculoskeletal (95%) and mucocutaneous (92%) systems; 2% cardiorespiratory and 2% renal organ domain involvement. At baseline, 95% had abnormal ANA, 40% were positive for anti-dsDNA antibodies; 33% of patients had abnormal C3, and 24% abnormal C4. Background SLE standard therapy included OCS (82%; mean daily dose, prednisone or equivalent, 9.8 mg), immunosuppressants (56%), and anti-malarials (80%). During Weeks 8-40, patients with a baseline OCS ≥10 mg/day were required to taper their OCS dose to ≤7.5 mg/day, unless there was worsening of disease activity.</paragraph> <paragraph>The primary endpoint was BICLA response rate measured at Week 52. At the interim analysis, SAPHNELO by subcutaneous administration demonstrated a statistically significant and clinically meaningful reduction of overall disease activity compared with placebo (Table 5).</paragraph> <table width="100%"> <caption>Table 5 BICLA Response Rate at Week 52 in Adults with Moderate to Severe SLE in Trial 5</caption> <col width="36%"/> <col width="32%"/> <col width="31%"/> <tbody> <tr> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"/> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">SAPHNELO 120 mg once weekly</content> </paragraph> <paragraph> <content styleCode="bold">(N=109)</content> </paragraph> </td> <td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Placebo</content> </paragraph> <paragraph> <content styleCode="bold">(N=111)</content> </paragraph> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">BICLA Response</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Toprule Botrule " valign="middle"> <list listType="ordered"> <item> <caption> </caption>Responder, n (%)<footnote ID="_Ref184320364">Per protocol, patients who used restricted medications beyond the protocol-specified thresholds, discontinued investigational product or died were considered non-responders.</footnote> </item> </list> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>64 (58.5)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>48 (43.2)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <list listType="ordered"> <item> <caption> </caption>Difference in Response Rates, % (95% CI)</item> </list> </td> <td align="center" colspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>15.3 (2.1, 28.5)</paragraph> <paragraph>p-value=0.0231<footnote ID="_Ref227590038">Based on an interim analysis using Pocock alpha spending function with an information fraction of 0.6. The primary endpoint was tested at the alpha level of 0.0354 at the interim analysis.</footnote> </paragraph> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Components of BICLA Response</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <list listType="ordered"> <item> <caption> </caption>BILAG Improvement, n (%)</item> </list> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>64 (58.5)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>48 (43.3)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <list listType="ordered"> <item> <caption> </caption>No Worsening of SLEDAI-2K, n (%)</item> </list> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>80 (73.4)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>77 (68.9)</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <list listType="ordered"> <item> <caption> </caption>No Worsening of PGA, n (%)</item> </list> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>80 (73.5)</paragraph> </td> <td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>78 (70.0)</paragraph> </td> </tr> <tr> <td colspan="3" styleCode="Toprule " valign="top"> <paragraph>The response rates, associated difference, and 95% CI are calculated using a Cochran-Mantel-Haenszel approach adjusted for stratification factors.</paragraph> </td> </tr> </tbody> </table> <paragraph>Subgroup analysis by disease severity (based on baseline SLEDAI-2K, <10 points, ≥10 points) and baseline OCS use (<10 mg/day, ≥10 mg/day) did not identify differences in response to SAPHNELO.</paragraph> </text> <effectiveTime value="20260424"/> </section> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_af944e10-8fd8-419c-96dd-4470fde6403e"> <id root="3decfe0f-0a69-49ed-8372-713611f4ef2b"/> <code code="34069-5" codeSystem="2.16.840.1.113883.6.1" displayName="HOW SUPPLIED SECTION"/> <title>16 HOW SUPPLIED/STORAGE AND HANDLING </title> <text> <paragraph> <content styleCode="underline">How Supplied</content> </paragraph> <paragraph>SAPHNELO (anifrolumab-fnia) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow solution in a single-dose vial for intravenous infusion or a prefilled syringe or autoinjector for subcutaneous injection.</paragraph> <paragraph>SAPHNELO is available as follows:</paragraph> <table styleCode="Noautorules" width="100%"> <col width="50%"/> <col width="50%"/> <tbody> <tr> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Packaging Unit and Strength</content> </paragraph> </td> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Pack Size and NDC</content> </paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>300 mg/2 mL (150 mg/mL) single-dose vial</paragraph> <paragraph>(NDC 0310-3040-00)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>One vial in a carton: NDC 0310-3040-00</paragraph> </td> </tr> <tr> <td styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>120 mg/0.8 mL single-dose prefilled syringe</paragraph> <paragraph>(NDC 0310-3080-75)</paragraph> </td> <td styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>One syringe in a carton: NDC 0310-3080-02</paragraph> </td> </tr> <tr> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>120 mg/0.8 mL single-dose autoinjector</paragraph> <paragraph>(SAPHNELO PEN) (NDC 0310-3080-25)</paragraph> </td> <td styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph>One autoinjector in a carton: NDC 0310-3080-01</paragraph> </td> </tr> </tbody> </table> <paragraph>The prefilled syringe (including needle cover) and autoinjector (including cap) are not made with natural rubber latex.</paragraph> <paragraph> <content styleCode="underline">Storage and Handling</content> </paragraph> <paragraph>Store SAPHNELO in a refrigerator at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light.</paragraph> <list listType="unordered"> <item> <caption>•</caption>Do not freeze. Do not shake. Do not expose to heat. Do not use SAPHNELO past the expiration date.</item> </list> <paragraph>If needed, SAPHNELO prefilled syringe or autoinjector can be stored at room temperature 68°F to 77°F (20°C to 25°C) for up to 7 days in the original carton to protect from light. After the SAPHNELO prefilled syringe or autoinjector has reached room temperature, do not return to the refrigerator. Discard SAPHNELO prefilled syringe or autoinjector if not used within 7 days at room temperature storage.</paragraph> </text> <effectiveTime value="20260424"/> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_756af5a2-a30f-42f4-ada3-8c3046e8ed2a"> <id root="305a6ae7-6bfc-4d9d-930a-56e9bfffd8d8"/> <code code="34076-0" codeSystem="2.16.840.1.113883.6.1" displayName="INFORMATION FOR PATIENTS SECTION"/> <title>17 PATIENT COUNSELING INFORMATION </title> <text> <paragraph>Advise the patient and/or caregiver to read the FDA-approved patient labeling (Patient Information and Instructions for Use).</paragraph> <paragraph> <content styleCode="underline">Serious Infections</content> </paragraph> <paragraph>Inform patients that SAPHNELO may decrease their ability to fight infections and that serious infections, including fatal ones, occurred in patients receiving SAPHNELO in clinical trials. Also inform patients that they are at increased risk of respiratory infections and herpes zoster during treatment with SAPHNELO <content styleCode="italics">[see <linkHtml href="#ID_0622efa7-563c-4bd1-a678-012b3c491247">Warnings and Precautions (5.1)</linkHtml>]</content>. Advise patients to contact their healthcare provider if they develop any symptoms of an infection.</paragraph> <paragraph> <content styleCode="underline">Hypersensitivity Reactions/Anaphylaxis</content> </paragraph> <paragraph>Inform patients that serious hypersensitivity reactions, including anaphylaxis, have been reported in patients who received SAPHNELO. Instruct patients to immediately tell their healthcare provider or go to the emergency department of their nearest hospital, if they experience symptoms of an allergic reaction (e.g., anaphylaxis) during or after the administration of SAPHNELO <content styleCode="italics">[see <linkHtml href="#ID_ac54e222-c42f-4bb9-ac2a-77059b3c7f5a">Warnings and Precautions (5.2)</linkHtml>]</content>.</paragraph> <paragraph> <content styleCode="underline">Immunizations</content> </paragraph> <paragraph>Inform patients that they should not receive live or live-attenuated vaccines while receiving SAPHNELO. Advise patients to discuss with their healthcare provider before seeking immunizations on their own <content styleCode="italics">[see <linkHtml href="#ID_74e712d3-7a99-4b92-8f3e-35f95c0b6b7c">Warnings and Precautions (5.4)</linkHtml>]</content>.</paragraph> <paragraph> <content styleCode="underline">Pregnancy</content> </paragraph> <paragraph>Advise female patients to inform their healthcare provider if they intend to become pregnant during therapy, suspect they are pregnant or become pregnant while receiving SAPHNELO <content styleCode="italics">[see <linkHtml href="#ID_14f23db1-eb47-44d5-b681-daed7d14b89c">Use in Specific Populations (8.1)</linkHtml>]</content>.</paragraph> <paragraph>Inform women that there is a pregnancy registry that monitors pregnancy outcomes in women exposed to SAPHNELO and they can contact AstraZeneca at 1-877-693-9268 for more information or to report the pregnancy.</paragraph> <paragraph>Manufactured by: AstraZeneca AB Södertälje, Sweden SE-15185</paragraph> <paragraph>US License No. 2059</paragraph> <paragraph>Distributed by: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850</paragraph> <paragraph>SAPHNELO is a registered trademark of AstraZeneca.</paragraph> <paragraph>©AstraZeneca 2026</paragraph> </text> <effectiveTime value="20260424"/> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_8f2c0fb5-6773-4ce8-9e63-8ca1aeb84abd"> <id root="af058ce7-12aa-40b5-95a5-c030c218fad7"/> <code code="42230-3" codeSystem="2.16.840.1.113883.6.1" displayName="SPL PATIENT PACKAGE INSERT SECTION"/> <text> <table width="100%"> <col width="50%"/> <col width="50%"/> <tbody> <tr> <td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">PATIENT INFORMATION</content> </paragraph> <paragraph> <content styleCode="bold">SAPHNELO<sup>®</sup> (saf-NEH-low)</content> </paragraph> <paragraph> <content styleCode="bold">(anifrolumab-fnia)</content> </paragraph> <paragraph> <content styleCode="bold">injection, for intravenous or subcutaneous use</content> </paragraph> </td> </tr> <tr> <td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">What is SAPHNELO?</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>SAPHNELO is a prescription medicine used to treat adults with moderate to severe systemic lupus erythematosus (SLE or lupus) who are receiving other lupus medicines.</item> <item> <caption>•</caption>SAPHNELO contains anifrolumab-fnia which is in a group of medicines called monoclonal antibodies. Lupus is a disease of the immune system (the body system that fights infection). When given together with other medicines for lupus, SAPHNELO may help to reduce your lupus disease activity more than other lupus medicines alone.</item> <item> <caption>•</caption>It is not known if SAPHNELO is effective in people with severe active lupus nephritis or central nervous system lupus.</item> <item> <caption>•</caption>It is not known if SAPHNELO is safe and effective in children.</item> </list> </td> </tr> <tr> <td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Do not use SAPHNELO if you:</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>are allergic to anifrolumab-fnia or any of the ingredients in SAPHNELO. See the end of this Patient Information leaflet for a complete list of ingredients in SAPHNELO.</item> </list> </td> </tr> <tr> <td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Before you receive SAPHNELO, tell your healthcare provider about all of your medical conditions, including if you:</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>think you have an infection or have infections that keep coming back. You should not receive SAPHNELO if you have an infection unless your healthcare provider tells you to. See <content styleCode="bold">“What are the possible side effects of SAPHNELO?”</content> </item> <item> <caption>•</caption>are scheduled to receive a vaccination or if you think you may need a vaccination. You should not receive live vaccines during treatment with SAPHNELO.</item> <item> <caption>•</caption>have or have had any type of cancer.</item> <item> <caption>•</caption>are receiving other biologic medicines or monoclonal antibodies.</item> <item> <caption>•</caption>are pregnant or plan to become pregnant. It is not known if SAPHNELO will harm your unborn baby. Tell your healthcare provider if you are pregnant, think you might be pregnant, or plan to become pregnant during your treatment with SAPHNELO.</item> <item> <caption>•</caption> <content styleCode="bold">Pregnancy Exposure Registry</content>. If you become pregnant while receiving SAPHNELO, talk to your healthcare provider. A pregnancy exposure registry monitors pregnancy outcomes in women exposed to SAPHNELO. You can find out more information about the registry by calling AstraZeneca at 1-877-693-9268.</item> <item> <caption>•</caption>are breastfeeding or plan to breastfeed. It is not known if SAPHNELO passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby while receiving SAPHNELO.</item> </list> <paragraph> <content styleCode="bold">Tell your healthcare provider about all the medicines you take,</content> including prescription and over-the-counter medicines, vitamins, and herbal supplements. SAPHNELO may affect the way other medicines work, and other medicines may affect how SAPHNELO works.</paragraph> </td> </tr> <tr> <td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">How will I receive SAPHNELO?</content> </paragraph> <paragraph> <content styleCode="bold">SAPHNELO is intended for use under your healthcare provider’s care and may be administered as an intravenous infusion or as a subcutaneous injection.</content> </paragraph> <paragraph> <content styleCode="bold">When given into a vein (intravenously)</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>Your healthcare provider will give you SAPHNELO through a needle placed in a vein (IV or intravenous infusion). It takes about 30 minutes to give you the full dose of SAPHNELO.</item> <item> <caption>•</caption>SAPHNELO is usually given 1 time every 4 weeks.</item> <item> <caption>•</caption>If you miss an appointment, call your healthcare provider as soon as possible to reschedule your appointment.</item> </list> <paragraph> <content styleCode="bold">When given under the skin (subcutaneously)</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>SAPHNELO may be prescribed as a single-dose prefilled syringe or as a single-dose autoinjector (SAPHNELO PEN).</item> <item> <caption>•</caption>Use SAPHNELO exactly as your healthcare provider tells you to use it.</item> <item> <caption>•</caption>SAPHNELO is injected under your skin (subcutaneously) in your stomach (abdomen), thigh or upper arm (for caregiver administration only) 1 time every week.</item> <item> <caption>•</caption>Before you use SAPHNELO, your healthcare provider will train you or your caregiver how to give the injections.</item> <item> <caption>•</caption>Read the <content styleCode="bold">Instructions for Use</content> that comes with SAPHNELO for information on how to prepare and inject SAPHNELO.</item> <item> <caption>•</caption>If you miss your dose of SAPHNELO inject a dose as soon as you remember. Then, continue to inject 1 time each week based on the new day SAPHNELO was injected or at your regularly scheduled time as long as there are at least 3‑days between the doses. In case you are not sure when to inject SAPHNELO, call your healthcare provider.</item> </list> </td> </tr> <tr> <td colspan="2" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">What are the possible side effects of SAPHNELO?</content> </paragraph> <paragraph> <content styleCode="bold">SAPHNELO may cause serious side effects, including:</content> </paragraph> </td> </tr> <tr> <td colspan="2" styleCode="Rrule Lrule " valign="top"> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Serious Infections.</content> SAPHNELO can lower the ability of your immune system to fight infections. You may be at a higher risk of developing respiratory infections, and shingles (herpes zoster) during treatment with SAPHNELO. Infections (including COVID-19) could be serious, leading to hospitalization or death. Tell your healthcare provider right away if you have any of the following symptoms of an infection:</item> </list> </td> </tr> <tr> <td styleCode="Lrule " valign="top"> <list listType="unordered"> <item> <caption>•</caption>fever, sweating, or chills</item> <item> <caption>•</caption>muscle aches</item> <item> <caption>•</caption>cough</item> <item> <caption>•</caption>shortness of breath</item> </list> </td> <td styleCode="Rrule " valign="top"> <list listType="unordered"> <item> <caption>•</caption>burning when urinating</item> <item> <caption>•</caption>urinating more often</item> <item> <caption>•</caption>diarrhea or stomach pain</item> <item> <caption>•</caption>warm, red, or painful skin or sores on your body.</item> </list> </td> </tr> <tr> <td colspan="2" styleCode="Rrule Lrule " valign="top"> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Allergic (hypersensitivity) reactions</content>, including anaphylaxis. Serious allergic reactions can happen during or after you get your SAPHNELO infusion or take your SAPHNELO injection. Tell your healthcare provider or get emergency help right away if you have any of the following symptoms of a serious allergic reaction:</item> </list> </td> </tr> <tr> <td styleCode="Lrule " valign="top"> <list listType="unordered"> <item> <caption>•</caption>swelling of your face, mouth, and tongue</item> <item> <caption>•</caption>breathing problems</item> </list> </td> <td styleCode="Rrule " valign="top"> <list listType="unordered"> <item> <caption>•</caption>fainting or dizziness</item> <item> <caption>•</caption>feeling lightheaded (low blood pressure)</item> </list> </td> </tr> <tr> <td colspan="2" styleCode="Rrule Lrule " valign="top"> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Cancer</content>. SAPHNELO may reduce the activity of your immune system. Medicines that affect the immune system may increase your risk of certain cancers.</item> </list> </td> </tr> <tr> <td colspan="2" styleCode="Rrule Lrule " valign="middle"> <paragraph> <content styleCode="bold">The most common side effects of SAPHNELO include:</content> </paragraph> </td> </tr> <tr> <td styleCode="Lrule " valign="top"> <list listType="unordered"> <item> <caption> </caption> <list listType="unordered"> <item> <caption>•</caption>upper respiratory infections</item> <item> <caption>•</caption>infusion reactions (when given intravenously)</item> <item> <caption>•</caption>cough</item> </list> </item> </list> </td> <td styleCode="Rrule " valign="top"> <list listType="unordered"> <item> <caption>•</caption>bronchitis</item> <item> <caption>•</caption>shingles (herpes zoster)</item> </list> </td> </tr> <tr> <td colspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">How should I store SAPHNELO?</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>Store SAPHNELO prefilled syringe and autoinjector in a refrigerator between 36°F to 46°F (2°C to 8°C) in the original carton to protect from light. </item> <item> <caption>•</caption>If needed, the SAPHNELO prefilled syringe or autoinjector (SAPHNELO PEN) can be stored at room temperature between 68°F to 77°F (20°C to 25°C) for up to 7 days in the original carton to protect from light. After the SAPHNELO prefilled syringe or autoinjector has reached room temperature, do not return to the refrigerator. Throw away SAPHNELO prefilled syringe or autoinjector if not used within 7 days at room temperature storage. </item> <item> <caption>•</caption>Do not shake SAPHNELO.</item> <item> <caption>•</caption>Do not freeze SAPHNELO.</item> <item> <caption>•</caption>Do not expose SAPHNELO to heat.</item> <item> <caption>•</caption>Do not use SAPHNELO past the expiration date.</item> <item> <caption>•</caption> <content styleCode="bold">Keep SAPHNELO and all medicines out of the reach of children.</content> </item> </list> </td> </tr> <tr> <td colspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph>These are not all of the possible side effects of SAPHNELO.</paragraph> <paragraph>Call your doctor for medical advice about side effects. You may report side effects to FDA at 1‑800‑FDA‑1088.</paragraph> </td> </tr> <tr> <td colspan="2" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <paragraph> <content styleCode="bold">General information about the safe and effective use of SAPHNELO</content> </paragraph> <paragraph>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use SAPHNELO for a condition for which it was not prescribed. Do not give SAPHNELO to other people, even if they have the same symptoms that you have. It may harm them. If you would like more information about SAPHNELO, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about SAPHNELO that is written for health professionals.</paragraph> </td> </tr> <tr> <td colspan="2" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">What are the ingredients in SAPHNELO?</content> </paragraph> <paragraph> <content styleCode="bold">Active ingredient:</content> anifrolumab-fnia</paragraph> <paragraph> <content styleCode="bold">Inactive ingredients: </content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>Intravenous infusion: L-histidine, L-histidine hydrochloride monohydrate, L-lysine hydrochloride, trehalose dihydrate, polysorbate 80 and Water for Injection.</item> <item> <caption>•</caption>Subcutaneous injection: histidine, L-histidine hydrochloride monohydrate, lysine hydrochloride, polysorbate 80, trehalose, and Water for Injection.</item> </list> <paragraph>The SAPHNELO prefilled syringe and autoinjector are not made with natural rubber latex.</paragraph> <paragraph>Manufactured by: AstraZeneca AB Södertälje, Sweden SE-15185</paragraph> <paragraph>Distributed by: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850</paragraph> <paragraph>©AstraZeneca 2026</paragraph> <paragraph>SAPHNELO is a registered trademark of AstraZeneca.</paragraph> <paragraph>For more information, go to <linkHtml href="https://www.saphnelo.com/">https://www.SAPHNELO.com</linkHtml> or call 1-800-236-9933.</paragraph> </td> </tr> <tr> <td colspan="2" valign="top"> <paragraph>This Patient Information has been approved by the U.S. Food and Drug Administration. Issued: April 2026</paragraph> </td> </tr> </tbody> </table> </text> <effectiveTime value="20260424"/> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_d6426925-cfc4-4776-a4fe-79559b3ee365"> <id root="fa3b778a-68ef-40e3-8dd3-4e8b395e0adc"/> <code code="59845-8" codeSystem="2.16.840.1.113883.6.1" displayName="INSTRUCTIONS FOR USE SECTION"/> <text> <table width="100%"> <col width="33%"/> <col width="33%"/> <col width="33%"/> <tbody> <tr> <td align="center" colspan="3" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">INSTRUCTIONS FOR USE</content> </paragraph> <paragraph> <content styleCode="bold">SAPHNELO® (saf-NEL-low)</content> </paragraph> <paragraph> <content styleCode="bold">(anifrolumab-fnia)</content> </paragraph> <paragraph> <content styleCode="bold">injection, for subcutaneous use</content> </paragraph> <paragraph> <content styleCode="bold">Single-dose prefilled syringe</content> </paragraph> <paragraph> <content styleCode="bold">120 mg/0.8 mL</content> </paragraph> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>This Instructions for Use contains information on how to inject using SAPHNELO prefilled syringe.</paragraph> <paragraph> <content styleCode="bold">Read this Instructions for Use before you start using SAPHNELO prefilled syringe and each time you get a refill. There may be new information.</content> This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.</paragraph> <paragraph>Your healthcare provider should show you or your caregiver how to use SAPHNELO prefilled syringe the right way. If you or your caregiver have any questions, talk to your healthcare provider. SAPHNELO prefilled syringe is for use under the skin (subcutaneous) only.</paragraph> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Important storage information and warnings</content> </paragraph> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule " valign="top"> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Store SAPHNELO prefilled syringe in a refrigerator between 36°F to 46°F (2°C to 8°C) in the original carton until ready to use.</content> </item> <item> <caption>•</caption>If needed, SAPHNELO prefilled syringe can be stored at room temperature between 68°F to 77°F (20°C to 25°C) for up to 7 days in the original carton to protect from light. After SAPHNELO prefilled syringe has reached room temperature, <content styleCode="bold">do not</content> return to the refrigerator. Throw away SAPHNELO prefilled syringe if not used within 7 days at room temperature. </item> <item> <caption>•</caption>Each SAPHNELO prefilled syringe contains 1 dose for one time use only. <content styleCode="bold">Do not</content> share SAPHNELO prefilled syringe with other people.</item> </list> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Do not</content> use SAPHNELO prefilled syringe if it has:</paragraph> <list listType="unordered"> <item> <caption>•</caption>been frozen or exposed to heat.</item> <item> <caption>•</caption>been dropped, damaged, or appears to be tampered with.</item> </list> <paragraph> <content styleCode="bold">Do not</content> shake SAPHNELO prefilled syringe.</paragraph> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>If any of the above happens, throw away the prefilled syringe in an FDA-cleared sharps disposal container and use a new prefilled syringe.</paragraph> <paragraph> <content styleCode="bold">Keep SAPHNELO prefilled syringe and all medicines out of the sight and reach of children.</content> </paragraph> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">SAPHNELO prefilled syringe parts</content> </paragraph> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Do not</content> remove the needle cover until right before injecting SAPHNELO.</paragraph> <paragraph> <content styleCode="bold">Do not</content> touch the needle guard activation clips. This will keep you from activating the needle guard too soon.</paragraph> </td> </tr> <tr> <td align="center" colspan="2" styleCode="Rrule Lrule Botrule " valign="top"> <renderMultiMedia ID="id-1741946956" referencedObject="ID_53cd53f2-07f7-40da-a03d-e289f04a28ef"/> </td> <td styleCode="Rrule Lrule Botrule " valign="top"> <renderMultiMedia ID="id-1322959805" referencedObject="ID_2c90f5f1-f1ae-4392-a5c5-7e0f69cd889f"/> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Preparing to inject using SAPHNELO prefilled syringe</content> </paragraph> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 1 – Gather supplies for your injection</content> </paragraph> </td> </tr> <tr> <td align="center" colspan="3" styleCode="Rrule Lrule " valign="top"> <renderMultiMedia ID="id-710032995" referencedObject="ID_9a9894dc-3ab9-4d26-a747-e4cbace75492"/> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>See Step 9 for instructions on how to throw away (dispose of) the used SAPHNELO prefilled syringe.</paragraph> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 2 – Inspect the carton and wait 60 minutes</content> </paragraph> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule " valign="top"> <paragraph>Select a clean, well-lit, flat work surface, such as a table.</paragraph> <paragraph> <content styleCode="bold">Check the expiration date (EXP) on the carton.</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Do not</content> use if the expiration date has passed.</item> </list> <paragraph>Check the carton for damage.</paragraph> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Do not</content> use if the carton looks damaged.</item> </list> </td> </tr> <tr> <td colspan="2" styleCode="Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Let SAPHNELO prefilled syringe come to room temperature for 60 minutes before injecting.</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>Keep SAPHNELO prefilled syringe in the original carton to protect from light.</item> <item> <caption>•</caption> <content styleCode="bold">Do not</content> warm SAPHNELO prefilled syringe in any other way. For example, <content styleCode="bold">do</content> <content styleCode="bold">not</content> warm it in a microwave, hot water, direct sunlight or near other heat sources.</item> </list> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <renderMultiMedia ID="id-924880122" referencedObject="E419043F-BF32-4965-9779-0D423AAF5677"/> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 3 – Remove the prefilled syringe from the carton and inspect</content> </paragraph> </td> </tr> <tr> <td colspan="2" styleCode="Lrule " valign="top"> <paragraph>Open the carton and remove SAPHNELO prefilled syringe by holding the middle of the syringe body.</paragraph> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Do not</content> hold or remove by the plunger.</item> </list> </td> <td align="center" rowspan="4" styleCode="Rrule " valign="middle"> <renderMultiMedia ID="id8732707" referencedObject="ID_34a09534-e81a-40ab-a3fa-6e93999b5dfa"/> </td> </tr> <tr> <td colspan="2" styleCode="Lrule " valign="top"> <paragraph> <content styleCode="bold">Check the expiration date on the prefilled syringe.</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Do not</content> use if the expiration date has passed.</item> </list> </td> </tr> <tr> <td colspan="2" styleCode="Lrule " valign="top"> <paragraph> <content styleCode="bold">Check the prefilled syringe for damage.</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Do not</content> use if damaged.</item> </list> </td> </tr> <tr> <td colspan="2" styleCode="Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Check the liquid through the viewing window.</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>The liquid should be clear and colorless to slightly yellow.</item> <item> <caption>•</caption> <content styleCode="bold">Do not</content> use if the liquid is cloudy, discolored, or contains visible particles.</item> <item> <caption>•</caption>It is normal to see small air bubbles in the liquid. <content styleCode="bold">Do not</content> try to remove the air bubbles.</item> </list> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Injecting using your SAPHNELO prefilled syringe</content> </paragraph> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 4 – Choose an injection site</content> </paragraph> </td> </tr> <tr> <td colspan="2" styleCode="Lrule Botrule " valign="top"> <paragraph>You or your caregiver can inject in the front of your thigh or the lower part of your stomach (abdomen).</paragraph> <paragraph>A caregiver may also inject your upper arm.</paragraph> <paragraph> <content styleCode="bold">Do not</content> try to inject yourself in the upper arm.</paragraph> <paragraph>Choose an injection site that is at least 1-inch (3 cm) away from where you last injected.</paragraph> <paragraph> <content styleCode="bold">Do not</content> inject:</paragraph> <list listType="unordered"> <item> <caption>•</caption>into the 2-inch (5 cm) area around your belly button.</item> <item> <caption>•</caption>where the skin is red, warm, tender, bruised, scaly or hard.</item> <item> <caption>•</caption>into scarred, damaged, discolored or tattooed skin. </item> <item> <caption>•</caption>through clothing.</item> </list> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <renderMultiMedia ID="id-1171949082" referencedObject="ID_179fdfa3-600d-40af-b2e5-632d21400bd3"/> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 5 – Wash your hands and clean the injection site</content> </paragraph> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule " valign="top"> <paragraph>Wash your hands well with soap and water.</paragraph> <paragraph>Clean the injection site with an alcohol wipe or with soap and water. Let the site air dry.</paragraph> </td> </tr> <tr> <td styleCode="Lrule Botrule " valign="top"> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Do not</content> touch the cleaned injection site again or blow on it before injecting.</item> </list> </td> <td align="center" styleCode="Botrule " valign="top"> <renderMultiMedia ID="id446054024" referencedObject="ID_67ac6be6-ab91-4027-aecf-214169c35e2b"/> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <renderMultiMedia ID="id968940658" referencedObject="ADE877E8-F2B8-469A-A099-D924B93F294E"/> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Step 6 – Pull off the needle cover</content> </paragraph> </td> </tr> <tr> <td colspan="2" styleCode="Lrule Botrule " valign="top"> <paragraph>Hold the SAPHNELO prefilled syringe body with 1 hand and carefully pull the needle cover straight off with your other hand.</paragraph> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Do not</content> twist or wiggle the needle cover to remove it.</item> <item> <caption>•</caption> <content styleCode="bold">Do not</content> touch or pull the plunger or plunger head while removing the needle cover.</item> <item> <caption>•</caption>You may see a drop of liquid at the end of the needle. This is normal.</item> <item> <caption>•</caption> <content styleCode="bold">Do not</content> recap the needle. Put the needle cover to the side to throw it in the trash later.</item> <item> <caption>•</caption> <content styleCode="bold">Do not</content> touch the needle or let it touch any surface.</item> <item> <caption>•</caption> <content styleCode="bold">Do not</content> use if the needle is damaged or dirty.</item> </list> <paragraph>Go to Step 7 right away after removing the needle cover.</paragraph> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <renderMultiMedia ID="id-1120680932" referencedObject="A2D3EA9A-D3FF-4D0A-A8CF-FBE2CA431138"/> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Step 7 – Injecting SAPHNELO</content> </paragraph> </td> </tr> <tr> <td colspan="2" styleCode="Lrule " valign="top"> <paragraph>Hold SAPHNELO prefilled syringe in 1 hand as shown. Use your other hand to gently pinch and hold the cleaned injection site.</paragraph> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Do not</content> press down on the plunger head until the needle is inserted into the skin.</item> <item> <caption>•</caption> <content styleCode="bold">Do not</content> pull back on the plunger head at any time.</item> </list> <paragraph>Inject using the SAPHNELO prefilled syringe by following the steps in figures <content styleCode="bold">a, b,</content> and <content styleCode="bold">c.</content> </paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <renderMultiMedia ID="id1036010072" referencedObject="ID_06aeb3bb-9496-4d90-aacc-7d8ea660e231"/> </td> </tr> <tr> <td align="center" styleCode="Lrule " valign="top"> <renderMultiMedia ID="id-535813857" referencedObject="ID_2a454b90-3d25-4ecd-9711-4f4302032d88"/> </td> <td align="center" valign="top"> <renderMultiMedia ID="id82039818" referencedObject="B63FDF8C-B981-4095-AE54-06B53CA6FCF0"/> </td> <td align="center" styleCode="Rrule " valign="top"> <renderMultiMedia ID="id315384925" referencedObject="F7E9E9C5-97E4-42B3-AD69-B6D7EACF5124"/> </td> </tr> <tr> <td styleCode="Lrule Botrule " valign="top"> <paragraph>Using a 45 degree angle, fully insert the needle into the pinched skin.</paragraph> <paragraph> <content styleCode="bold">Do not</content> reposition the SAPHNELO prefilled syringe after you insert the needle into the skin.</paragraph> </td> <td styleCode="Botrule " valign="top"> <paragraph>Use your thumb to push down the plunger head.</paragraph> <paragraph>To make sure you inject all the medicine and activate the needle guard, keep pushing firmly on the plunger head until it is fully down as far as it will go.</paragraph> </td> <td styleCode="Rrule Botrule " valign="top"> <paragraph>Slowly let go of the plunger head until the needle guard covers the needle.</paragraph> <paragraph>If the needle is not covered, carefully throw away (dispose of) the SAPHNELO prefilled syringe right away (see Step 9).</paragraph> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 8 – Check the injection site</content> </paragraph> </td> </tr> <tr> <td colspan="2" styleCode="Lrule Botrule " valign="top"> <paragraph>There may be a small amount of blood or liquid at the injection site. This is normal.</paragraph> <paragraph>If needed, press a cotton ball or gauze on the area and apply a small bandage.</paragraph> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Do not</content> rub the injection site.</item> </list> </td> <td align="center" styleCode="Rrule Botrule " valign="top"> <renderMultiMedia ID="id1073931530" referencedObject="ID_5cfdb262-81d3-4e4e-8fae-e9c61bfb2680"/> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 9 – Throw away (dispose of) the used SAPHNELO prefilled syringe</content> </paragraph> </td> </tr> <tr> <td colspan="2" styleCode="Lrule " valign="top"> <paragraph>Each prefilled syringe contains 1 single-dose of SAPHNELO and <content styleCode="bold">cannot be used again. Do not</content> recap the needle.</paragraph> <paragraph>Put your used SAPHNELO prefilled syringe in an FDA-cleared <content styleCode="bold">sharps disposal container </content>right away after use.</paragraph> <paragraph> <content styleCode="bold">Do not</content> throw away (dispose of) SAPHNELO prefilled syringe in your household trash.</paragraph> </td> <td align="center" styleCode="Rrule " valign="top"> <renderMultiMedia ID="id-1288424264" referencedObject="ID_923bc8d5-7550-4217-ab72-99675b6c457c"/> </td> </tr> <tr> <td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>If you do not have an FDA-cleared sharps disposal container, you may use a household container that is: </paragraph> <list listType="unordered"> <item> <caption>•</caption>made of a heavy-duty plastic,</item> <item> <caption>•</caption>can be closed with a tight-fitting puncture resistant lid, without sharps being able to come out,</item> <item> <caption>•</caption>upright and stable during use,</item> <item> <caption>•</caption>leak resistant, and</item> <item> <caption>•</caption>properly labelled to warn of hazardous waste inside the container.</item> </list> <paragraph>When your sharp disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. </paragraph> <paragraph>There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: <linkHtml href="http://www.fda.gov/safesharpsdisposal">http://www.fda.gov/safesharpsdisposal</linkHtml>.</paragraph> <paragraph> <content styleCode="bold">Do not</content> dispose of your used sharps disposal container in your household trash unless your community guidelines permit this.</paragraph> <paragraph> <content styleCode="bold">Do not</content> recycle your used sharps disposal container.</paragraph> <paragraph>Manufactured by: </paragraph> <paragraph>AstraZeneca AB, Södertälje, Sweden SE-15185</paragraph> <paragraph>US License No. 2059</paragraph> <paragraph>Distributed by: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850</paragraph> <paragraph>©AstraZeneca 2026</paragraph> <paragraph>SAPHNELO is a registered trademark of AstraZeneca.</paragraph> <paragraph>For more information, go to <linkHtml href="https://www.SAPHNELO.com">https://www.SAPHNELO.com</linkHtml> or call 1-800-236-9933.</paragraph> </td> </tr> <tr> <td colspan="3" styleCode="Toprule " valign="top"> <paragraph>This Instructions for Use has been approved by the U.S. Food and Drug Administration Approved: April 2026</paragraph> </td> </tr> </tbody> </table> </text> <effectiveTime value="20260424"/> <component> <observationMedia ID="ID_53cd53f2-07f7-40da-a03d-e289f04a28ef"> <text>pre-filled-syringe-parts-before-use</text> <value mediaType="image/jpeg"> <reference value="pre-filled-syringe-parts-before-use.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="ID_2c90f5f1-f1ae-4392-a5c5-7e0f69cd889f"> <text>pre-filled-syringe-parts-after-use</text> <value mediaType="image/jpeg"> <reference value="pre-filled-syringe-parts-after-use.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="ID_9a9894dc-3ab9-4d26-a747-e4cbace75492"> 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<?xml version="1.0" encoding="UTF-8"?><section ID="ID_aecd2708-dd5a-4132-b618-5e9ac51029e2"> <id root="96be5556-d613-4355-a25e-8a84226c4bc4"/> <code code="59845-8" codeSystem="2.16.840.1.113883.6.1" displayName="INSTRUCTIONS FOR USE SECTION"/> <text> <table width="100%"> <col width="26%"/> <col width="5%"/> <col width="3%"/> <col width="20%"/> <col width="11%"/> <col width="3%"/> <col width="33%"/> <tbody> <tr> <td align="center" colspan="7" styleCode="Rrule Botrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">INSTRUCTIONS FOR USE</content> </paragraph> <paragraph> <content styleCode="bold">SAPHNELO® PEN (saf-NEL-low)</content> </paragraph> <paragraph> <content styleCode="bold">(anifrolumab-fnia)</content> </paragraph> <paragraph> <content styleCode="bold">injection, for subcutaneous use</content> </paragraph> <paragraph> <content styleCode="bold">Single-dose Autoinjector</content> </paragraph> <paragraph> <content styleCode="bold">120 mg/0.8 mL</content> </paragraph> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>This Instructions for Use contains information on how to inject using SAPHNELO PEN.</paragraph> <paragraph> <content styleCode="bold">Read this Instructions for Use before you start using SAPHNELO PEN and each time you get a refill. There may be new information.</content> This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.</paragraph> <paragraph>Your healthcare provider should show you or your caregiver how to use SAPHNELO PEN the right way. If you or your caregiver have any questions, talk to your healthcare provider. SAPHNELO PEN is for use under the skin (subcutaneous) only.</paragraph> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Important storage information and warnings</content> </paragraph> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule " valign="top"> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Store SAPHNELO PEN in a refrigerator between 36°F to 46°F (2°C to 8°C) in the original carton until ready to use.</content> </item> <item> <caption>•</caption>If needed, SAPHNELO PEN can be stored at room temperature between 68°F to 77°F (20°C to 25°C) for up to 7 days in the original carton to <content styleCode="bold">protect from light</content>. After SAPHNELO PEN has reached room temperature, <content styleCode="bold">do not</content> return to the refrigerator. Throw away SAPHNELO PEN if not used within 7 days at room temperature. </item> <item> <caption>•</caption>Each SAPHNELO PEN contains 1 dose for one time use only. <content styleCode="bold">Do not</content> share SAPHNELO PEN with other people.</item> </list> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Do not</content> use SAPHNELO PEN if it has:</paragraph> <list listType="unordered"> <item> <caption>•</caption>been frozen or exposed to heat.</item> <item> <caption>•</caption>been dropped, damaged, or appears to be tampered with.</item> </list> <paragraph> <content styleCode="bold">Do not</content> shake SAPHNELO PEN.</paragraph> <paragraph>If any of the above happens, throw away SAPHNELO PEN in an FDA-cleared sharps disposal container and use a new SAPHNELO PEN.</paragraph> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Keep SAPHNELO PEN and all medicines out of the sight and reach of children.</content> </paragraph> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">SAPHNELO PEN parts</content> </paragraph> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Do not</content> remove the cap until right before injecting SAPHNELO.</paragraph> <paragraph> <content styleCode="bold">Do not</content> touch the green needle guard.</paragraph> </td> </tr> <tr> <td colspan="4" styleCode="Rrule Lrule Botrule " valign="top"> <renderMultiMedia ID="id-1203009594" referencedObject="FFD84A04-9428-4644-BA40-373178789E01"/> </td> <td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"> <renderMultiMedia ID="id85356233" referencedObject="AE8419A5-031B-4264-8029-47468910FE73"/> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Preparing to inject using SAPHNELO PEN</content> </paragraph> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 1 – Gather supplies for your injection</content> </paragraph> </td> </tr> <tr> <td align="center" colspan="7" styleCode="Rrule Lrule " valign="top"> <renderMultiMedia ID="id1503771252" referencedObject="ID_8be5bd2d-21b5-4870-81f6-fdd99f98c1da"/> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>See Step 10 for instructions on how to throw away (dispose of) the used SAPHNELO PEN.</paragraph> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 2 – Inspect the carton and wait 60 minutes</content> </paragraph> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule " valign="top"> <paragraph>Select a clean, well-lit, flat work surface, such as a table.</paragraph> <paragraph> <content styleCode="bold">Check the expiration date (EXP) on the carton.</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Do not</content> use if the expiration date has passed.</item> </list> <paragraph>Check the carton for damage.</paragraph> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Do not</content> use if the carton looks damaged.</item> </list> </td> </tr> <tr> <td colspan="4" styleCode="Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Let SAPHNELO PEN come to room temperature for 60 minutes before injecting.</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>Keep SAPHNELO PEN in the original carton to protect from light.</item> <item> <caption>•</caption> <content styleCode="bold">Do not</content> warm SAPHNELO PEN in any other way. For example, <content styleCode="bold">do not</content> warm it in a microwave, hot water, direct sunlight or near other heat sources.</item> </list> </td> <td align="center" colspan="3" styleCode="Rrule Botrule " valign="top"> <renderMultiMedia ID="id1164205228" referencedObject="ID_4714068c-48d2-4595-a169-255bd2f0f395"/> </td> </tr> <tr> <td colspan="4" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 3 – Remove SAPHNELO PEN from the carton and inspect</content> </paragraph> </td> <td align="center" colspan="3" rowspan="5" styleCode="Rrule Lrule Toprule Botrule " valign="top"> <renderMultiMedia ID="id1235819760" referencedObject="ID_80b77464-cd16-4ae9-908b-ff3115549e0a"/> </td> </tr> <tr> <td colspan="4" styleCode="Rrule Lrule " valign="top"> <paragraph>Open the carton and remove SAPHNELO PEN by gently grasping the middle of the device.</paragraph> </td> </tr> <tr> <td colspan="4" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Check the expiration date on SAPHNELO PEN. </content> </paragraph> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Do not</content> use if the expiration date has passed.</item> </list> </td> </tr> <tr> <td colspan="4" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Check SAPHNELO PEN for damage.</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Do not</content> use if damaged.</item> </list> </td> </tr> <tr> <td colspan="4" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Check the liquid through the viewing window.</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>The liquid should be clear and colorless to slightly yellow.</item> <item> <caption>•</caption> <content styleCode="bold">Do not</content> use if the liquid is cloudy, discolored, or contains visible particles.</item> <item> <caption>•</caption>It is normal to see small air bubbles in the liquid. </item> </list> <paragraph> <content styleCode="bold"> Do not</content> try to remove the air bubbles.</paragraph> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Injecting using your SAPHNELO PEN</content> </paragraph> </td> </tr> <tr> <td colspan="4" styleCode="Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 4 – Choose an injection site</content> </paragraph> </td> <td colspan="3" styleCode="Rrule Toprule " valign="top"/> </tr> <tr> <td colspan="4" styleCode="Lrule Botrule " valign="top"> <paragraph>You or your caregiver can inject in the front of your thigh or the lower part of your stomach (abdomen).</paragraph> <paragraph>A caregiver may also inject you in your upper arm.</paragraph> <paragraph> <content styleCode="bold">Do not</content> try to inject yourself in the upper arm.</paragraph> <paragraph>Choose an injection site that is at least 1-inch (3 cm) away from where you last injected.</paragraph> <paragraph> <content styleCode="bold">Do not </content>inject:</paragraph> <list listType="unordered"> <item> <caption>•</caption>into the 2-inch (5 cm) area around your belly button.</item> <item> <caption>•</caption>where the skin is red, warm, tender, bruised, scaly or hard.</item> <item> <caption>•</caption>into scarred, damaged, discolored or tattooed skin. </item> <item> <caption>•</caption>through clothing.</item> </list> </td> <td align="center" colspan="3" styleCode="Rrule Botrule " valign="top"> <renderMultiMedia ID="id-1192297862" referencedObject="ID_2f7dd0a9-3f75-4c19-9a8f-6cf94b1199b0"/> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 5 – Wash your hands and clean the injection site</content> </paragraph> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule " valign="top"> <paragraph>Wash your hands well with soap and water.</paragraph> <paragraph>Clean the injection site with an alcohol wipe or with soap and water. Let the site air dry.</paragraph> </td> </tr> <tr> <td styleCode="Lrule Botrule " valign="top"> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Do not</content> touch the cleaned injection site again or blow on it before injecting.</item> </list> </td> <td align="center" colspan="3" styleCode="Rrule Botrule " valign="top"> <renderMultiMedia ID="id1593427512" referencedObject="ID_4164df6c-5f30-46e7-92a7-2a0acda9d436"/> </td> <td align="center" colspan="3" styleCode="Rrule Lrule Botrule " valign="top"> <renderMultiMedia ID="id-904224176" referencedObject="ID_9a22cdb5-23e0-41a5-907c-e4922982a45d"/> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 6 – Pull off the cap</content> </paragraph> </td> </tr> <tr> <td colspan="4" styleCode="Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Do not</content> remove the cap until you are ready to inject.</paragraph> <paragraph>Pull off the cap (protective sleeve inside).</paragraph> <list listType="unordered"> <item> <caption>•</caption>SAPHNELO PEN is now unlocked and ready to inject.</item> <item> <caption>•</caption> <content styleCode="bold">Do not</content> touch the green needle guard or the needle inside.</item> <item> <caption>•</caption> <content styleCode="bold">Do not</content> recap SAPHNELO PEN. This could cause the medicine to come out too soon or damage SAPHNELO PEN.</item> </list> <paragraph>Go to Step 7 right away after removing the cap.</paragraph> </td> <td colspan="3" styleCode="Rrule Botrule " valign="top"> <renderMultiMedia ID="id949742982" referencedObject="CD3519A2-C36C-4D12-BFE6-C244D419DAE9"/> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 7 – Injecting SAPHNELO</content> </paragraph> </td> </tr> <tr> <td colspan="4" styleCode="Lrule " valign="top"> <paragraph>Inject the medicine using SAPHNELO PEN by following the steps in figures <content styleCode="bold">a, b, c, and d</content>.</paragraph> <paragraph>To deliver a full dose, <content styleCode="bold">press and hold SAPHNELO PEN for about 15 seconds</content> until the green plunger fills the viewing window. </paragraph> <paragraph>You may hear a <content styleCode="bold">first ‘click’</content> at the start of the injection and a <content styleCode="bold">second ‘click’ </content>at the end of the injection.</paragraph> <paragraph> <content styleCode="bold">Do not</content> move or change the position of SAPHNELO PEN after the injection has started.</paragraph> </td> <td align="center" colspan="3" styleCode="Rrule " valign="top"> <renderMultiMedia ID="id-1811631008" referencedObject="ID_65d0bff9-7806-41b1-a9ea-740e95cd6c58"/> </td> </tr> <tr> <td colspan="4" styleCode="Lrule " valign="top"/> <td colspan="3" styleCode="Rrule " valign="top"> <paragraph> <content styleCode="bold">Position SAPHNELO PEN.</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>Place the green needle guard flat against the skin (90-degree angle). </item> <item> <caption>•</caption>Make sure you can see the viewing window.</item> </list> </td> </tr> <tr> <td align="center" colspan="2" styleCode="Lrule " valign="top"> <renderMultiMedia ID="id2049632768" referencedObject="CBB8E856-B812-4C94-8CEA-A85B22778565"/> </td> <td align="center" colspan="3" valign="top"> <renderMultiMedia ID="id1984812067" referencedObject="ID_06b77d66-1799-4f8a-a7df-fb3431b33a79"/> </td> <td align="center" colspan="2" styleCode="Rrule " valign="top"> <renderMultiMedia ID="id-1631938498" referencedObject="D2394445-F8A7-444E-9000-582C15A8BA99"/> </td> </tr> <tr> <td colspan="3" styleCode="Lrule Botrule " valign="top"> <paragraph> <content styleCode="bold">Press down firmly and hold against skin.</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>You may hear the <content styleCode="bold">first click</content> right away. This tells you the injection has started.</item> <item> <caption>•</caption>The green plunger will move down in the viewing window.</item> </list> </td> <td colspan="3" styleCode="Botrule " valign="top"> <paragraph> <content styleCode="bold">Hold down firmly for about 15 seconds.</content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>The green plunger will fill the viewing window.</item> <item> <caption>•</caption>You may hear the <content styleCode="bold">second click</content> at the end of injection.</item> </list> </td> <td styleCode="Rrule Botrule " valign="top"> <paragraph> <content styleCode="bold">After you have completed your injection, lift SAPHNELO PEN straight up. </content> </paragraph> <list listType="unordered"> <item> <caption>•</caption>The green needle guard will slide down and lock into place over the needle.</item> </list> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Step 8 – Check the viewing window</content> </paragraph> </td> </tr> <tr> <td colspan="4" styleCode="Lrule " valign="top"> <paragraph>Check the viewing window to make sure all the medicine has been injected.</paragraph> <paragraph>If the green plunger does not fill the viewing window, you may not have received the full dose.</paragraph> <list listType="unordered"> <item> <caption>•</caption>If this happens or if you have any other concerns, contact your healthcare provider.</item> </list> </td> <td align="center" colspan="3" styleCode="Rrule " valign="top"> <renderMultiMedia ID="id1786685947" referencedObject="A9675D0D-8A3B-424D-9462-77A46E4BB2B5"/> </td> </tr> <tr> <td align="center" colspan="4" styleCode="Lrule Botrule " valign="top"> <renderMultiMedia ID="id1137070486" referencedObject="ID_789e106f-c970-48dc-9277-a8cec02ffbce"/> </td> <td colspan="3" styleCode="Rrule Botrule " valign="top"/> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule " valign="top"> <paragraph> <content styleCode="bold">Step 9 – Check the injection site</content> </paragraph> </td> </tr> <tr> <td colspan="4" styleCode="Lrule Botrule " valign="top"> <paragraph>There may be a small amount of blood or liquid at the injection site. This is normal.</paragraph> <paragraph>If needed, press a cotton ball or gauze on the area and apply a small bandage.</paragraph> <list listType="unordered"> <item> <caption>•</caption> <content styleCode="bold">Do not</content> rub the injection site.</item> </list> </td> <td align="center" colspan="3" styleCode="Rrule Botrule " valign="top"> <renderMultiMedia ID="id-1704863539" referencedObject="ID_7b81a153-0907-4b47-bd62-096049d08355"/> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule Toprule " valign="top"> <paragraph> <content styleCode="bold">Step 10 – Throw away (dispose of) the used SAPHNELO PEN</content> </paragraph> </td> </tr> <tr> <td colspan="4" styleCode="Lrule " valign="top"> <paragraph>Put your used SAPHNELO PEN in an FDA-cleared <content styleCode="bold">sharps disposal container</content> right away after use.</paragraph> <paragraph> <content styleCode="bold">Do not</content> throw away (dispose of) SAPHNELO PEN in your household trash.</paragraph> </td> <td align="center" colspan="3" styleCode="Rrule " valign="top"> <renderMultiMedia ID="id-1985460222" referencedObject="AD50D4A0-F3AD-4731-8B1B-E81D61CA8608"/> </td> </tr> <tr> <td colspan="7" styleCode="Rrule Lrule Botrule " valign="top"> <paragraph>If you do not have an FDA-cleared sharps disposal container, you may use a household container that is: </paragraph> <list listType="unordered"> <item> <caption>•</caption>made of a heavy-duty plastic,</item> <item> <caption>•</caption>can be closed with a tight-fitting puncture resistant lid, without sharps being able to come out,</item> <item> <caption>•</caption>upright and stable during use,</item> <item> <caption>•</caption>leak resistant, and</item> <item> <caption>•</caption>properly labelled to warn of hazardous waste inside the container.</item> </list> <paragraph>When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container.</paragraph> <paragraph>There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at: <linkHtml href="http://www.fda.gov/safesharpsdisposal">http://www.fda.gov/safesharpsdisposal</linkHtml>.</paragraph> <paragraph> <content styleCode="bold">Do not</content> dispose of your used sharps disposal container in your household trash unless your community guidelines permit this.</paragraph> <paragraph> <content styleCode="bold">Do not</content> recycle your used sharps disposal container.</paragraph> <paragraph>Manufactured by: </paragraph> <paragraph>AstraZeneca AB, Södertälje, Sweden SE-15185</paragraph> <paragraph>US License No. 2059</paragraph> <paragraph>Distributed by: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850</paragraph> <paragraph>©AstraZeneca 2026</paragraph> <paragraph>SAPHNELO is a registered trademark of AstraZeneca.</paragraph> <paragraph>For more information, go to <linkHtml href="https://www.SAPHNELO.com">https://www.SAPHNELO.com</linkHtml> or call 1-800-236-9933.</paragraph> </td> </tr> <tr> <td colspan="7" styleCode="Toprule " valign="top"> <paragraph>This Instructions for Use has been approved by the U.S. Food and Drug Administration Approved: April 2026</paragraph> </td> </tr> </tbody> </table> </text> <effectiveTime value="20260424"/> <component> <observationMedia ID="FFD84A04-9428-4644-BA40-373178789E01"> <text>pen-parts-before-use</text> <value mediaType="image/jpeg"> <reference value="pen-parts-before-use.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="AE8419A5-031B-4264-8029-47468910FE73"> <text>pen-parts-after-use</text> <value mediaType="image/jpeg"> <reference value="pen-parts-after-use.jpg"/> </value> </observationMedia> </component> <component> <observationMedia ID="ID_8be5bd2d-21b5-4870-81f6-fdd99f98c1da"> <text>pen-step-1</text> <value mediaType="image/jpeg"> <reference value="pen-step-1.jpg"/> </value> 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<?xml version="1.0" encoding="UTF-8"?><section ID="ID_3fc79dd7-039f-4038-839b-d8e138acca0e"> <id root="428a27aa-e8c8-4407-a324-75b303e350ca"/> <code code="51945-4" codeSystem="2.16.840.1.113883.6.1" displayName="PACKAGE LABEL.PRINCIPAL DISPLAY PANEL"/> <title>PACKAGE/LABEL PRINCIPAL DISPLAY PANEL </title> <text> <paragraph>NDC 0310-3080-02 <content styleCode="bold">Rx only</content> </paragraph> <paragraph> <content styleCode="bold">SAPHNELO<sup>®</sup> </content> </paragraph> <paragraph>(anifrolumab-fnia)</paragraph> <paragraph>Injection</paragraph> <paragraph>120 mg/0.8 mL</paragraph> <paragraph>For Subcutaneous Injection only</paragraph> <paragraph>Do not shake, freeze or expose to heat.</paragraph> <paragraph>1 single-dose pre-filled syringe</paragraph> <paragraph>AstraZeneca</paragraph> <renderMultiMedia ID="id-1437358972" referencedObject="b02b6a8b-29b9-49b9-ad40-7b52fc3f185d"/> </text> <effectiveTime value="20260424"/> <component> <observationMedia ID="b02b6a8b-29b9-49b9-ad40-7b52fc3f185d"> <text>Carton_1_Sub_Cut_Inj_120mg_zero_point_8ml</text> <value mediaType="image/jpeg"> <reference value="Carton_1_Sub_Cut_Inj_120mg_zero_point_8ml.jpg"/> </value> </observationMedia> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_0F16AE59-3888-48B7-BAB6-95058BD03591"> <id root="8b8eadb3-be1e-4c4a-b3b3-0f5961211569"/> <code code="51945-4" codeSystem="2.16.840.1.113883.6.1" displayName="PACKAGE LABEL.PRINCIPAL DISPLAY PANEL"/> <title>PACKAGE/LABEL PRINCIPAL DISPLAY PANEL </title> <text> <paragraph>NDC 0310-3080-01 Rx Only</paragraph> <paragraph>Saphnelo® Pen 120 mg/0.8 mL</paragraph> <paragraph>(anifrolumab-fnia)</paragraph> <paragraph>Injection </paragraph> <paragraph>For Subcutaneous Injection Only</paragraph> <paragraph>Do not shake, freeze, or expose to heat.</paragraph> <paragraph>1 single-dose autoinjector </paragraph> <paragraph>AstraZeneca</paragraph> <renderMultiMedia ID="id1521272987" referencedObject="E69BAD24-676B-43B5-812C-B358A8CFF41C"/> </text> <effectiveTime value="20260424"/> <component> <observationMedia ID="E69BAD24-676B-43B5-812C-B358A8CFF41C"> <text>Carton_2_Autoinjector_SubCut_Pen</text> <value mediaType="image/jpeg"> <reference value="Carton_2_Autoinjector_SubCut_Pen.jpg"/> </value> </observationMedia> </component> </section>

<?xml version="1.0" encoding="UTF-8"?><section ID="ID_1D199C90-6589-4184-BAFB-BCA328013B3C"> <id root="c185910c-7f73-4c0b-880a-34290e1a91b7"/> <code code="51945-4" codeSystem="2.16.840.1.113883.6.1" displayName="PACKAGE LABEL.PRINCIPAL DISPLAY PANEL"/> <title>PACKAGE/LABEL PRINCIPAL DISPLAY PANEL </title> <text> <paragraph>NDC 0310-3040-00 Rx Only</paragraph> <paragraph> <content styleCode="bold">SAPHNELO</content>®</paragraph> <paragraph>(anifrolumab-fnia)</paragraph> <paragraph>Injection</paragraph> <paragraph>300 mg/ 2 mL</paragraph> <paragraph>(150 mg/mL)</paragraph> <paragraph>For Intravenous Infusion After Dilution</paragraph> <paragraph>Must dilute before use. See prescribing information.</paragraph> <paragraph>Single-dose vial. Discard unused portion.</paragraph> <paragraph>Store refrigerated at 2<sup>o</sup>C to 8<sup>o</sup>C (36<sup>o</sup>F to 46<sup>o</sup>F)</paragraph> <paragraph>Keep vial in original carton to protect from light.</paragraph> <paragraph>Do not shake or freeze.</paragraph> <paragraph>1 single-dose vial</paragraph> <paragraph>AstraZeneca</paragraph> <renderMultiMedia ID="id-662317157" referencedObject="ID_4aac9e75-bfaa-446a-b19b-cbdedb01ca79"/> </text> <effectiveTime value="20260424"/> <component> <observationMedia ID="ID_4aac9e75-bfaa-446a-b19b-cbdedb01ca79"> <text>saphnelo_vial</text> <value mediaType="image/jpeg"> <reference value="saphnelo_vial.jpg"/> </value> </observationMedia> </component> </section>

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