Acelyrin announces izokibep trial did not meet primary endpoint

Acelyrin announced top-line results from Part B of a Phase 2b/3 trial evaluating izokibep for the treatment of moderate-to-severe Hidradenitis Suppurativa, or HS. The primary endpoint of HiSCR75 at week 16 did not meet statistical significance. However, response rates for izokibep showed early HiSCR100 responses, a clear dose-effect supported by both pharmacokinetic exposures and HiSCR responses favoring 160mg weekly dosing, and no evidence of safety or tolerability limitation. The randomized double-blind, placebo-controlled, multi-center trial evaluated the safety and efficacy of izokibep dosed 160 mg weekly and every two weeks, versus placebo, in 175 patients with moderate-to-severe HS. The trial was conducted at 50 sites globally and assessed various efficacy endpoints, including the primary endpoint of HiSCR75 at 16 weeks utilizing a non-responder imputation analysis method. In the primary NRI analysis of Part B, statistical significance was impacted by patients with HiSCR75-100 discontinuing as early as week 4 unrelated to adverse events. In addition, there was a marked increase in placebo rates during the course of the study. Applying a Last Observation Carried Forward, or LOCF, sensitivity analysis of the full dataset highlighted the impact of responder discontinuations on the primary analysis and showed statistical significance of HiSCR75 at week 16. An independently conducted pre-planned interim analysis, to which the company remained blinded until the time of this primary analysis, occurred prior to a rise in placebo rates observed later in the trial. Also, given the number of responders who discontinued in the QW arm – the majority unrelated to an adverse event – a modified-NRI approach showed a high level of statistical significance and highlighted the impact of discontinuations on magnitude and significance of response. This analysis demonstrates the performance of izokibep at this juncture in the study – in isolation from the placebo rate increases observed later in the trial – and provides an exploratory approach to analyzing responder discontinuations. The safety profile for izokibep was consistent with prior studies and the anti-IL-17A class. There were no events of candida in the high dose 160mg QW arm and there were two discontinuations across the trial due to injection site reactions. The company said it is in a strong financial position and expects its existing cash to fund operations through key value-driving milestones across our portfolio. Cash, cash equivalents and short-term marketable securities totaled $823M at June 30. Top-line data for the ongoing placebo-controlled Phase 2b/3 trial in PsA and proof-of-concept data for lonigutamab in thyroid eye disease are expected by end of Q1.