Acelyrin's Izokibep Fails to Meet Primary Endpoint in Phase 2b/3 Hidradenitis Suppurativa Trial
核心洞察
Acelyrin's izokibep, an IL-17A inhibitor, did not meet the primary endpoint of HiSCR75 in a Phase 2b/3 trial for hidradenitis suppurativa (搜索) (HS).
The HiSCR75 response rate at week 16 was 39% for izokibep (160 mg weekly) and 29% for placebo, failing to demonstrate a statistically significant treatment effect (p=0.3278).
Despite the primary endpoint failure, post-hoc analyses showed stronger efficacy signals related to HiSCR100, indicating potential for complete disease resolution.
Acelyrin's investigational IL-17A inhibitor, izokibep, failed to meet the primary endpoint in its Phase 2b/3 clinical trial (NCT05355805) for the treatment of moderate-to-severe hidradenitis suppurativa (搜索) (HS). The trial results indicated an unexpected increase in placebo response, contributing to the non-significant treatment effect observed.
Trial Details and Results
The Phase 2b/3 trial enrolled 175 patients with moderate-to-severe HS, who were administered 160 mg doses of izokibep either once or twice weekly. The primary endpoint was the proportion of patients achieving at least a 75% reduction from baseline in Hidradenitis Suppurativa (搜索) Clinical Response Score (HiSCR75) at week 16, assessed using a non-responder imputation (NRI) method. The study revealed that 39% of patients treated with izokibep once weekly achieved HiSCR75, compared to 29% in the placebo group (p=0.3278). The twice-weekly izokibep group showed a 34% HiSCR75 response rate, also not statistically significant compared to placebo.
Data Analysis and Discontinuation Rates
Acelyrin reported that high rates of discontinuation early in the trial negatively affected the NRI analysis. To account for this, a last observation carried forward (LOCF) sensitivity analysis was conducted, which showed that the once-weekly dosing of izokibep was significantly better than placebo in inducing HiSCR75 at week 16. A modified NRI analysis also indicated higher HiSCR75 rates with izokibep compared to placebo, with strong statistical significance.
HiSCR100 Observations
Despite the failure to achieve statistical significance in the primary NRI analysis, Acelyrin noted stronger efficacy signals related to HiSCR100, defined as a 100% decrease in scores from baseline. According to Acelyrin's CEO Shao-Lee Lin, the consistent and early achievement of HiSCR100, along with prior experience in Psoriatic Arthritis, continues to demonstrate the potential of izokibep for resolution of disease, especially in difficult-to-treat tissues.
Safety and Ongoing Trial
The safety profile of izokibep in this trial was consistent with previous reports. A total of 31 patients discontinued the trial, with most discontinuations being unrelated to adverse events. Acelyrin is currently conducting a Phase 3 trial (NCT05905783) to further investigate izokibep for HS.