お知らせ • Dec 12
Q32 Bio Provides Bempikibart Program Update, Including Next Steps for Advancing Alopecia Areata Development Program
Q32 Bio Inc. announced topline results from the SIGNAL-AA Phase 2a signal finding clinical trial evaluating bempikibart (ADX-914), which identified encouraging clinical activity in patients with alopecia areata. The Company plans to expand the SIGNAL-AA Phase 2a clinical trial and enroll additional patients evaluating bempikibart in AA. The Company is also providing an update on the SIGNAL-AD clinical trial in patients with atopic dermatitis. Although the Company is reporting promising findings in Part A, the trial did not meet its primary endpoint in Part B. Q32 Bio plans to conduct a review of the results. Topline Results from SIGNAL-AA Phase 2a Clinical Trial: SIGNAL-AA is a Phase 2a, randomized, double-blind, placebo-controlled, multi-center clinical trial evaluating bempikibart in adult patients with severe and very severe AA (baseline Severity of Alopecia Tool (SALT) scores of 50-100) treated over 24 weeks, with follow-up through 36 weeks. The study is being conducted to evaluate the efficacy and safety of bempikibart 200 mg administered subcutaneously, every-other-week (Q2W) compared to placebo. A total of 44 patients were enrolled in the trial with a primary endpoint of the mean relative percent change in SALT score at 24 weeks compared with baseline. Following database lock, one site was excluded from the efficacy analysis based on marked protocol violations of entry criteria. This resulted in the removal of three placebo patients, rendering the planned statistical analyses for the primary endpoint inappropriate due to the reduced sample size. On a post-hoc analysis of the remaining per-protocol population of patients with AA (n=27), bempikibart demonstrated an improvement in hair re-growth compared to placebo: At week 24: patients treated with bempikibart showed a mean reduction in SALT score of 16% in the bempikibart group vs a reduction of 2% in the placebo group. A Wilcoxon Rank Sum test yielded a p-value of 0.045. At week 24: 9% of bempikibart patients in the trial achieved a SALT-20 (SALT score less than or equal to 20) compared to 0% in placebo. At week 26: 13% of bempikibart patients achieved SALT-20 compared 0% in placebo. Bempikibart was observed to be safe and well tolerated in the SIGNAL-AA trial. There were no serious adverse events or Grade 3 or higher adverse events related to treatment. Q32 Bio plans to enroll approximately 20 additional patients in a Part B expansion of the SIGNAL-AA Phase 2a clinical trial to further evaluate bempikibart in AA, including a loading regimen. The Company will defer enrollment into the planned Phase 2 clinical trial of ADX-097 in ANCA-Associated Vasculitis (AAV), previously expected to begin in 2025, to focus efforts on continued enrollment in the ongoing bempikibart AA and ADX-097 renal basket Phase 2 clinical trials. Topline Results from SIGNAL-AD Phase 2a Clinical Trial: SIGNAL-AD is a two-part Phase 2a, randomized, double-blind, placebo-controlled, multi-center clinical trial evaluating bempikibart in adult patients with persistent, moderate-to-severe AD. Part A (n=15) was conducted to evaluate safety, pharmacokinetics (PK), and to enable dose selection for Part B of the clinical trial. Part A was randomized 2:1 between bempikibart and placebo in each of two dose cohorts of 2mg/kg or 3mg/kg Q2W SC for 12 weeks. In Part A, at week 14, improvement in average EASI score from baseline was 58% in patients treated with 2mg/kg Q2W SC and 84% in patients treated at 3mg/kg Q2W SC, and 72% on a pooled basis, compared to 38% in patients treated with placebo. In Part B, which evaluated both efficacy and safety of bempikibart compared to placebo, patients were enrolled 1:1 in the bempikibart 200 mg Q2W SC (n=52) and placebo (n=54) arms for 12 weeks of treatment. The primary endpoint is the mean percent change from baseline to week 14 in the Eczema Area and Severity Index (EASI) score. At week 14, data from Part B demonstrated that patients treated with bempikibart showed a 74% improvement in average EASI from baseline, compared to 76% for the placebo group (p= not statistically significant). Results of the primary endpoint were generally consistent when stratified for pre-specified baseline entry criteria. Bempikibart was observed to be safe and well tolerated in the SIGNAL-AD trial. There were no serious adverse events (SAE) or Grade 3 or higher adverse events related to treatment. Q32 Bio plans to conduct a review of the SIGNAL-AD results. Biomarker Results in SIGNAL-AD and SIGNAL-AA: Across SIGNAL-AD and SIGNAL-AA, bempikibart at 200mg Q2W SC demonstrated favorable PK and target engagement as demonstrated by substantial reductions in biomarkers of Th2 and Th1. These results include: A reduction in Th2 biomarkers, including TARC, IgE and eosinophils, which was consistent with the type of biomarker impact previously observed with other agents that have demonstrated utility in atopic dermatitis, such as IL-4Ra, IL-13 and OX40 ligand-targeted agents. An expected modulation of T-cells, with a 20-30% reduction, consistent with target engagement and IL-7Ra blockade. Q32 Bio believes these results demonstrate that bempikibart is a potent inhibitor of both TSLP and IL-7 signaling as evidenced by robust changes in both Th2 biomarkers and T-cells. The Company believes the mechanism of action of bempikibart has the potential to be active in other Th2 and Th1 driven diseases, including asthma, COPD, ulcerative colitis (UC), rheumatoid arthritis (RA), celiac disease, multiple sclerosis (MS) and others. The Company has published an updated investor presentation with additional details regarding the bempikibart update for review by interested parties.