Anifrolumab

SAPHNELO is indicated for the treatment of adult patients with moderate to severe systemic lupus erythematosus (SLE), who are receiving standard therapy. Limitations of Use 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. 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.

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. 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.

• The recommended intravenous dosage is 300 mg every 4 weeks. • The recommended subcutaneous dosage is 120 mg once every week. • See Full Prescribing Information for complete preparation and administration information.

SAPHNELO is contraindicated in patients with a history of anaphylaxis with anifrolumab-fnia.

• 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. • Hypersensitivity Reactions Including Anaphylaxis: Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported. • Malignancy: Consider the individual benefit-risk in patients with known risk factors for malignancy prior to prescribing SAPHNELO. • Immunizations: Avoid use of live or live-attenuated vaccines in patients receiving SAPHNELO. • Not Recommended for Use with Other Biologic Therapies.

The following clinically significant adverse reactions are also discussed elsewhere in the labeling: • Serious Infections • Hypersensitivity Reactions Including Anaphylaxis • Malignancy Most common adverse drug reactions (incidence ≥5%) are nasopharyngitis, upper respiratory tract infections, bronchitis, infusion related reactions, herpes zoster and cough.

No formal drug interaction trials have been conducted.

Store SAPHNELO in a refrigerator at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light. • Do not freeze. 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 protected 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. Do not shake.