By SPC News Staff
The FDA approved anifrolumab-fnia (Saphnelo, AstraZeneca), a first-in-class treatment for adults with moderate to severe systemic lupus erythematosus (SLE) who are receiving standard therapy.

This marks the first regulatory approval for a type I interferon (type I IFN) receptor antagonist and the only new treatment approved for SLE in more than 10 years. Type I IFN plays a central role in the pathophysiology of lupus. Increased type I IFN signaling is associated with increased disease activity and severity.

The approval was based on efficacy and safety data from the anifrolumab-fnia clinical development program, including two TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) phase 3 trials and the MUSE phase 2 trial. In these trials, more patients treated with anifrolumab-fnia experienced a reduction in overall disease activity across organ systems, including skin and joints, and achieved a sustained reduction in oral corticosteroid (OCS) use compared with placebo, with both groups receiving standard therapy.

All three trials (TULIP-1, TULIP-2 and MUSE) were randomized, double-blind, 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).

The pivotal TULIP phase 3 program included two trials, TULIP-1 and TULIP-2, which evaluated the efficacy and safety of anifrolumab-fnia versus placebo. TULIP-2 demonstrated superiority across multiple efficacy end points versus placebo with both arms receiving standard therapy. In the trial, 362 eligible patients were randomized (1:1) and received a fixed-dose IV infusion of 300 mg of anifrolumab-fnia or placebo every four weeks. 

In TULIP-1, 457 eligible patients were randomized (1:2:2) and received a fixed-dose IV infusion of 150 mg of anifrolumab-fnia, 300 mg of anifrolumab-fnia or placebo every four weeks, in addition to standard therapy. The trial did not meet its primary end point based on the SLE Responder Index 4 composite measure (Lancet Rheumatol 2019;1[4]E208-E219).

TULIP-2 assessed the effectiveness of anifrolumab-fnia  in reducing disease activity as measured by the BILAG-Based Composite Lupus Assessment scale (N Engl J Med 202;382:211-221).

The MUSE phase 2 trial (ClinicalTrials.gov Identifier: NCT01438489; https://clinicaltrials.gov/ct2/show/NCT01438489) evaluated the efficacy and safety of two doses of anifrolumab-fnia versus placebo. In MUSE, 305 adults were randomized and received a fixed-dose IV infusion of 300 mg of anifrolumab-fnia, 1,000 mg of the drug or placebo every four weeks, in addition to standard therapy, for 48 weeks. The trial showed improvement versus placebo across multiple efficacy end points, with both arms receiving standard therapy (Arthritis Rheum 2016 Nov 7.  https://doi.org/10.1002/art.39962).

“Our treatment goals in systemic lupus erythematosus are to reduce disease activity, prevent organ damage from either the illness itself or the medications, especially steroids, and improve one’s quality of life. Today’s approval of anifrolumab represents a big step forward for the entire lupus community. Physicians will now be able to offer an effective new treatment that has produced significant improvements in overall disease activity, while reducing corticosteroid use,” said Richard Furie, MD, the chief of the Division of Rheumatology at Northwell Health, in Great Neck, N.Y., and a principal investigator in the Saphnelo clinical development program.

The adverse reactions that occurred more frequently in patients who received anifrolumab-fnia in the three clinical trials included nasopharyngitis, upper respiratory tract infection, bronchitis, infusion-related reactions, herpes zoster and cough. For more information, see the package insert.

As the most common form of lupus affecting up to 300,000 people in the United States, SLE disproportionately affects the Black, Hispanic and Asian populations. It is a complex autoimmune condition that can affect any organ, and people often experience debilitating symptoms, long-term organ damage and poor health-related quality of life.