August 02, 2021
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FDA approves Saphnelo, first new lupus treatment since 2011

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The FDA has approved AstraZeneca’s anifrolumab-fnia, a first-in-class type I interferon receptor antagonist, for treatment of adults with moderate to severe systemic lupus erythematosus, according to a press release.

Over the last 50 years, SLE has garnered only a single FDA-approved therapy — belimumab (Benlysta, GlaxoSmithKline) in 2011 — and only narrowly, as its multicenter phase 2 trial failed to meet its primary endpoints. After 10 years and a similar series of disappointing clinical trials, anifrolumab-fnia (Saphnelo) has finally broken the lupus drug drought.

The FDA has approved Saphnelo for the treatment of adult systemic lupus erythematosus patients with moderate to severe disease, ending a decade-long drought in the lupus armamentarium. Source: Adobe Stock

“The lupus community needs more tools in their toolbox,” Richard Furie, MD, chief of the division of rheumatology at Northwell Health, and professor of medicine at Hofstra/Northwell School of Medicine in New York, told Healio Rheumatology. “We need more drugs, and it’s not for lack of trying. It’s just that lupus is incredibly difficult — it’s a hard nut to crack, as they say.”

“We have been trying since the early 1990s to get drugs approved, not only for systemic lupus but also lupus nephritis,” Furie said. “Although there has been unprecedented clinical trial activity, it’s so hard developing drugs for lupus; we have had failure after failure after failure. Belimumab obviously was an exception, and in December and January, we had two back-to-back drug approvals for lupus nephritis. And now we have anifrolumab, which gives the clinicians more resources to treat their patients.”

Richard Furie

The FDA based its approval on efficacy and safety data from results from the phase 3 TULIP-1 and TULIP-2 trials, as well as the phase 2 MUSE trial. In TULIP-1, 457 patients were randomized to receive either a fixed-dose intravenous infusion of 150 mg Saphnelo, 300 mg Saphnelo or placebo every 4 weeks, in addition to standard therapy. However, the trial failed to meet its primary endpoint based on the SLE Responder Index 4 (SRI4) composite measure.

Data from the follow-up TULIP-2 trial demonstrated superiority across multiple efficacy endpoints vs. placebo with both groups receiving standard therapy. In the trial, 362 patients were randomized to receive either a fixed-dose intravenous infusion of 300 mg 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.

In the accompanying MUSE trial, 305 adults were randomized to receive either a fixed-dose intravenous infusion of 300 mg Saphnelo, 1,000 mg Saphnelo or placebo every 4 weeks, in addition to standard therapy, for 48 weeks. The trial showed improvement compared with placebo across multiple efficacy endpoints with both groups receiving standard therapy.

“If you line up all these metrics — for both TULIP-1 and TULIP-2, and the phase 2 program — there are far many more successful outcomes than unsuccessful outcomes,” Furie said in an interview. “It just so happens one of the unsuccessful outcomes was the TULIP-1 primary endpoint. But, again, that speaks to how difficult lupus clinical trials are, and speaks to the fact that we need to learn why the SRI and the BICLA had discordant outcomes. I think one needs to look at all of the data.”

Pooled safety and efficacy data from these trials demonstrated that more patients treated with Saphnelo experienced a reduction in overall disease activity across organ systems, including skin and joints, and achieved sustained reduction in oral corticosteroid use compared to placebo, with both groups receiving standard therapy.

Gregg J. Silverman

“I’m quite pleased and gratified that anifrolumab was able to get the approval from the FDA based on the success of the TULIP-1 and TULIP-2 trials,” Gregg J. Silverman, MD, director of the Laboratory of B Cell Immunobiology at the NYU Langone School of Medicine, told Healio Rheumatology. “In light of the fact that 60% to 80% of adults with lupus have some level of type-1 interferon signature, this really promises to change our approach to the treatment of lupus, with our patients greatly benefiting.”

“This is also a major step toward better identifying what the right agent is for the right patient, because lupus is a very heterogenous disease,” Silverman noted. “I think everyone agrees that there has been a sort of a lumping together of individuals with very different disease manifestations. However, we haven’t really had a clear consensus of how to disentangle it other than the organ system involvement. Now we have a mechanism, first identified decades ago, which has been validated as an important therapeutic target.”

He added that “this approval means that we will be able to treat our patients more effectively, while hopefully avoiding broad-spectrum nonspecific immunosuppressives and even cytotoxic agents. In addition, this drug promises to reduce the use of corticosteroids, which carry a heavy burden of toxicity in our patients.”

According to the FDA, the most common adverse events associated with Saphnelo included nasopharyngitis, upper respiratory tract infection, bronchitis, infusion-related reactions, herpes zoster and cough. AstraZeneca has reported that Saphnelo is under regulatory review for SLE in Europe and Japan. A phase 3 trial in SLE using subcutaneous delivery has been initiated with additional phase 3 trials planned for lupus nephritis, cutaneous lupus erythematosus and myositis.