The Food and Drug Administration (FDA) has approved Saphnelo (anifrolumab-fnia) for the treatment of adults with moderate to severe systemic lupus erythematosus who are receiving standard therapy.
Type I interferons (IFNs) play a role in the pathogenesis of systemic lupus erythematosus (SLE). Anifrolumab-fnia, a human immunoglobulin G1 kappa monoclonal antibody, binds to subunit 1 of the type I IFN receptor and blocks the biologic activity of type I IFNs.
The approval was based on data from three 52-week, multicenter, randomized, double-blind, placebo-controlled studies (ClinicalTrials.gov Identifier: MUSE [NCT01438489], TULIP-1 [NCT02446912] and TULIP-2 [NCT02446899]), which evaluated the efficacy and safety of anifrolumab-fnia in adults with moderate to severe SLE. All patients received standard therapy, which included at least 1 of the following: oral corticosteroids (OCS), antimalarials, and immunosuppressants (methotrexate, azathioprine or mycophenolate mofetil).
In the TULIP-1 trial, 457 patients were randomly assigned 1:2:2 to receive anifrolumab-fnia 150mg, 300mg, or placebo via IV infusion every 4 weeks. In the TULIP-2 trial, 362 patients were randomly assigned 1:1 to receive anifrolumab-fnia 300mg or placebo via IV infusion every 4 weeks. The primary endpoint for both trials was the improvement in disease activity at 52 weeks, measured by SRI-4 in TULIP-1 and the British Isles Lupus Assessment Group based Composite Lupus Assessment (BICLA) in TULIP-2.
In the TULIP-1 trial, treatment with anifrolumab-fnia did not meet the primary endpoint on the SRI4 composite measure. However, results suggested a clinical benefit for anifrolumab-fnia compared with placebo based on key secondary endpoints including the reduction in OCS dose, Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) responses and BICLA responses.
Findings from the TULIP-2 trial showed a statistically significant and clinically meaningful reduction in disease activity at week 52, with 47.8% of patients receiving anifrolumab-fnia 300mg responding compared with 31.5% of patients on placebo (difference in response rates, 16.3%; 95% CI, 6.3-26.3; P =.001). Treatment with anifrolumab-fnia was also associated with a statistically significant reduction in OCS use and improvement in skin manifestations.
With regard to safety, the most common adverse reactions reported were nasopharyngitis, upper respiratory tract infection, bronchitis, infusion related reactions, herpes zoster and cough.
Saphnelo is supplied as a 2mL single-dose vial containing 300mg of anifrolumab-fnia and is expected to be available at the end of August 2021.
The use of Saphnelo is not recommended in patients with severe active lupus nephritis or severe active central nervous system lupus.
- Saphnelo (anifrolumab) approved in the US for moderate to severe systemic lupus erythematosus. News release. AstraZeneca. Accessed August 2, 2021. https://www.businesswire.com/news/home/20210802005199/en/SAPHNELO-anifrolumab-Approved-in-the-US-for-Moderate-to-Severe-Systemic-Lupus-Erythematosus.
- Saphnelo [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals; 2021.