One year after flop, AstraZeneca's phase 3 lupus trial hits endpoint 

A phase 3 trial of AstraZeneca’s anifrolumab in systemic lupus erythematosus has met its primary endpoint. The success comes one year after the anti-IFNAR1 antibody failed to move the needle in another late-phase lupus trial.

AstraZeneca’s latest lupus trial, TULIP 2, enrolled 373 patients and randomized them to receive 300 mg of anifrolumab or placebo every four weeks, plus standard of care. After 52 weeks, AstraZeneca found patients who received anifrolumab experienced a greater reduction in disease activity as measured by the British Isles Lupus Assessment Group Based Composite Lupus Assessment.

The outcome represents a reversal of fortunes for anifrolumab. One year ago, AstraZeneca reported that the first, 460-patient phase 3 trial failed to reduce disease activity by more than placebo. The phase 3 fail looked like the beginning of the end for anifrolumab.

“It is disappointing for patients. It is disappointing for us, of course, but that is what we do. We take calculated risks on a variety of products in our pipeline,” AstraZeneca CEO Pascal Soriot told investors shortly after reporting data from the first phase 3.

The more positive data come from a trial that differs from its predecessor in some important ways. Notably, the original trial used a different scale, namely the SLE Responder Index 4, to assess the effect of anifrolumab on disease activity. AstraZeneca also tested two doses, 300 mg and 150 mg, in the original trial.

AstraZeneca Executive Vice President Mene Pangalos and his colleagues will now review the full data set and look into how they can get the drug to market. While the failed phase 3 is a black mark against anifrolumab, the unmet need in lupus could enable AstraZeneca to win approval on the strength of imperfect data.

GlaxoSmithKline won FDA approval for Benlysta in 2011, ending a 50-year wait for a new lupus treatment. The approval marked the start of the era of biologic treatments for lupus, but other companies have been unable to follow GSK’s lead. Over the past 18 months, lupus drugs in development at Ablynx, Biogen and Xencor have all failed clinical tests.