General Information

Saphnelo (anifrolumab-fnia) is a a type I interferon (IFN) receptor antagonist.

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

Saphnelo is supplied as a solution for intravenous infusion. Saphnelo must be diluted prior to intravenous administration. The recommended dosage of Saphnelo is 300 mg, administered as an intravenous infusion over a 30-minute period, every 4 weeks. If a planned infusion is missed, administer Saphnelo as soon as possible. Maintain a minimum interval of 14 days between infusions.

Mechanism of Action

Saphnelo (anifrolumab-fnia) a 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.

Clinical Trial Results

The FDA approval of Saphnelo was based on the phase 3 trials TULIP-1 and TULIP-2 and the phase 2 MUSE trial. All three trials were randomized, double-blinded, placebo-controlled trials in patients with moderate to severe SLE who were receiving standard therapy. Standard therapy included at least one of the following: OCS, antimalarials and immunosuppressants (methotrexate, azathioprine or mycophenolate mofetil).

TULIP-2 randomized 362 eligible patients (1:1) to and receive a fixed-dose intravenous infusion of 300mg Saphnelo or placebo every four weeks. TULIP-2 assessed the effect of Saphnelo in reducing disease activity as measured by the BILAG-Based Composite Lupus Assessment (BICLA) scale. TULIP-2 demonstrated superiority across multiple efficacy endpoints versus placebo with both arms receiving standard therapy. In TULIP-1, 457 eligible patients were randomized (1:2:2) and received a fixed-dose intravenous infusion of 150mg Saphnelo, 300mg Saphnelo or placebo every four weeks, in addition to standard therapy. The trial did not meet its primary endpoint based on the SLE Responder Index 4 (SRI4) composite measure.

The MUSE Phase II trial evaluated the efficacy and safety of two doses of Saphnelo versus placebo. In MUSE, 305 adults were randomized and received a fixed-dose intravenous infusion of 300mg Saphnelo, 1,000mg Saphnelo or placebo every four weeks, in addition to standard therapy, for 48 weeks. The trial showed improvement versus placebo across multiple efficacy endpoints with both arms receiving standard therapy.