After a 10-year drought in new treatments for systemic lupus, the FDA has waved through a new drug.
The FDA cleared AstraZeneca’s Saphnelo (anifrolumab) to treat moderate to severe systemic lupus erythematosus (SLE), the most common form of lupus, the company said Monday.
It marks the first U.S. go-ahead for SLE in about 10 years, after GlaxoSmithKline’s Benlysta broke nearly five decades of stagnancy in the field with an FDA approval in 2011.
AstraZeneca has touted Saphnelo’s blockbuster potential, given SLE affects up to 300,000 people in the U.S. An Evaluate Pharma tally of analyst estimates put Saphnelo’s 2026 sales at $488 million.
Benlysta last year ginned up £719 million—and 19% growth—mainly thanks to increased use of an under-the-skin formulation approved in 2017. The GSK drug is well on track to bust the blockbuster threshold this year with first-half sales of £392 million ($545 million) on the strength of a 30% increase in sales.
Unlike Benlysta, which inhibits B-cell stimulating factor, Saphnelo is a type I interferon receptor antagonist, and it’s the first drug in its class to cross the regulatory finish line.
There’s apparently room for both drugs in SLE. As of 2020, over 80% of U.S. SLE patients who were eligible for Benlysta weren’t on the drug, GSK pharma chief Luke Miels said during a conference call in February.
Saphnelo’s approval isn't without controversy; the drug’s two phase 3 programs were a hit and a miss. The phase 3 Tulip-1 trial found the drug didn’t outperform placebo at helping patients achieve a response on a well-validated lupus disease activity assessment called SLE Responder Index 4 (SRI-4). Even though a post hoc analysis painted Saphnelo in a slightly better light, especially on markers such as reduction in oral steroid use, it still failed to claim a win.
Learning from that flop, AstraZeneca shifted the primary endpoint of the second trial, Tulip-2, midway through. It abandoned SRI-4 to another composite clinical measure called the BILAG-Based Composite Lupus Assessment (BICLA).
It worked. At the one-year mark, 47.8% of patients on Saphnelo had achieved the BICLA marker, versus 31.5% for patients in the control arm. But the results were mixed: Saphnelo again showed better outcomes on oral steroid use, and it offered improvements per a disease severity index called CLASI, but it fell short on two other important secondary endpoints, namely, the number of swollen or tender joints and the annualized flare rate.
Both SRI-4 and BICLA are validated lupus markers. SRI-4 measures complete response—though only in some lupus symptoms—while BICLA captures partial benefits but requires improvement in all organs.
GSK’s Benlysta may not be Saphnelo’s only competition for long, though. Eli Lilly and Incyte are testing their JAK inhibitor, Olumiant, for SLE in the phase 3 Brave I and Brave II trials with SRI-4 as the primary endpoint.
Saphnelo’s commercial success could also come from its potential to reach lupus nephritis, which is inflammation of the kidney caused by SLE.
Benlysta in December became the first drug approved by the FDA for patients with active lupus nephritis, and Aurinia’s Lupkynis quickly followed with a go-ahead in January. AZ, for its part, recently completed the phase 2 Tulip-LN trial, in which Saphenlo, at a high dose, showed some improvements in lupus nephritis on a kidney function marker that measured the amount of protein in the urine.