Nektar Therapeutics’ hopes of rebuilding its battered business around lupus lie in tatters. The key phase 2 clinical trial of rezpegaldesleukin missed its primary endpoint, prompting partner Eli Lilly to drop plans for further development in lupus and reassess its next steps in atopic dermatitis.
After seeing its Bristol Myers Squibb-partnered oncology asset bempegaldesleukin flame out in phase 3, Nektar sought to regroup around the Lilly-partnered rezpeg, a PEG conjugate of recombinant IL-2, and the cancer therapy NKTR-255. The midphase readout in systemic lupus erythematosus represented a big early test of Nektar’s plans. Nektar failed the test—and its stock fell 38% to $1.83 in premarket trading.
The phase 2 study randomized 291 adults with moderate to severe lupus to receive one of three doses of rezpeg, delivered subcutaneously every two weeks, or placebo. After 24 weeks, the pooled subjects on rezpeg performed no better on the SLEDAI-2K lupus activity index than their peers on placebo did.
At the low and high doses, 300 mcg and 1800 mcg, the proportion of participants who experienced (PDF) a four-point or greater reduction on SLEDAI-2K was almost identical to the result in the placebo cohort. The middle dose performed better, beating placebo by 8.8 percentage points on the SLEDAI-2K endpoint, but the difference still fell short of statistical significance. Lilly has seen enough in lupus.
“They have said they do not plan to move forward in lupus. I think that's very disappointing, but that's their decision. We are having discussions with them regarding how we move forward in atopic dermatitis and other indications,” Nektar CEO Howard Robin said on a conference call with investors. “Nektar is not going to be moving it forward in phase 3 either at this point. We have to focus on the best prospects.”
Nektar continues to see a future for rezpeg in atopic dermatitis. In January, Robin made the case that key differences between lupus and other autoimmune diseases means the failure in one indication doesn’t preclude continued development in other conditions. And Nektar repeated the message after the phase 2 failure in lupus.
Lilly has already run a 12-week clinical trial of rezpeg in atopic dermatitis, which Jonathan Zalevsky, Ph.D., chief research and development officer at Nektar, said found “activity that was right in the range of dupixent.” The biotech had been preparing to run a phase 2b study in the indication when the lupus bombshell landed. Nektar is now talking to Lilly about potential modifications to the design and conduct of the clinical trial.
As well as drawing a distinction between the lupus efficacy data and odds of success in atopic dermatitis, Nektar sought to allay concerns that the 39.7% discontinuation rate at the 1800-mcg dose is a cause for concern. “We don't think it has a negative read-through on studying the drug in other indications, such as atopic dermatitis,” Zalevsky said on the call. Your move, Lilly.