Acelyrin’s Hidradenitis Suppurativa Drug Misses Mark, but Hope Persists
In a rollercoaster ride for Acelyrin, the company revealed top-line data from a Phase IIb/III trial that showed its much-anticipated IL-17A inhibitor, izokibep, falling short of its primary endpoint in patients battling hidradenitis suppurativa, a stubborn chronic skin condition. The results, announced on Monday, sent shockwaves through the biopharma world.
The trial involved patients receiving 160-mg doses of izokibep either once or twice weekly. Dishearteningly, the data showed that 39% of patients on the once-weekly schedule achieved a 75% reduction in the hidradenitis suppurativa clinical response (HiSCR75) score at 16 weeks, while 29% of those on a placebo regimen reached a similar level. The gap wasn’t statistically significant, dealing a blow to Acelyrin’s hopes, with a p-value of 0.3278.
Even the twice-weekly izokibep regimen failed to distinguish itself from placebo, with only 34% of patients hitting the HiSCR75 mark at 16 weeks. These figures were computed using a non-responder imputation (NRI) method.
The market responded swiftly to the news, with Acelyrin’s shares plummeting by a staggering 64% in after-hours trading.
The trial, known as Part B, was a double-blinded and placebo-controlled Phase IIb/III study, enrolling 175 patients grappling with moderate-to-severe hidradenitis suppurativa. High discontinuation rates as early as four weeks into the trial seemed to negatively affect the primary endpoint. Additionally, an unexpected surge in placebo response further blurred the picture.
In an effort to account for the dropouts, Acelyrin employed the last observation carried forward (LOCF) sensitivity method, which did highlight a significant advantage for the once-weekly schedule in inducing HiSCR75 at week 16.
Furthermore, a modified NRI analysis, which factored in discontinuations, showed izokibep outperforming placebo with strong statistical significance.
Despite missing its primary endpoint, Acelyrin’s CEO, Shao-Lee Lin, expressed optimism, noting “consistent early and high orders of response.” She pointed to izokibep’s promising results in achieving HiSCR100, representing a complete score reduction, and its prior success in Psoriatic Arthritis trials as a testament to its potential for disease resolution in challenging cases.
While the road ahead may be uncertain, Acelyrin soldiers on with an ongoing Phase III izokibep trial for hidradenitis suppurativa, initiated in June 2023. Notably, the company completed its IPO in May 2023, raising an impressive $540 million, signaling a strong commitment to their research and development efforts.