Fulcrum Therapeutics Announces Positive Initial Results from the 20 mg Dose Cohort of the Phase 1b PIONEER Trial of Pociredir in Sickle Cell Disease at the 67th American Society of Hematology Annual Meeting

Core Insights - Fulcrum Therapeutics reported positive initial results from the 20 mg dose cohort of the Phase 1b PIONEER trial for pociredir in sickle cell disease, showing a clear dose-response and clinically meaningful increases in fetal hemoglobin (HbF) levels [1][2][4] Trial Design and Data Overview - The PIONEER trial is a Phase 1b open-label dose-escalation study evaluating pociredir's safety and efficacy in adult patients with severe sickle cell disease, with the 20 mg cohort consisting of 12 adults [3][13] - As of the November 11, 2025 data cutoff, all 12 patients completed the Week 6 visit, and 6 patients reached the Week 12 visit [3] Efficacy Data - At Week 6, the mean absolute HbF increased by 9.9% in the 20 mg cohort, with 58% of patients achieving HbF levels ≥20% [4][10] - A >3.75-fold mean induction of HbF was observed at Week 12 in the 20 mg cohort compared to a 2.4-fold induction in the 12 mg cohort [4][5] - The proportion of F-cells increased from 31% at baseline to 58% at Week 6, indicating early progression toward pan-cellular HbF induction [10] Safety Profile - Pociredir was generally well-tolerated, with no treatment-related serious adverse events reported as of the November 11, 2025 data cutoff [1][11] - The safety profile observed in the 20 mg cohort remained consistent with previously reported safety data from the 12 mg cohort [10][11] Future Plans - Fulcrum plans to host an investor event on December 7, 2025, to discuss the results from the PIONEER trial [1][7] - Updated results from the trial are expected to be reported in Q1 2026 [3]