Fulcrum Therapeutics’ pociredir shows efficacy in sickle cell disease

Fulcrum Therapeutics (FULC) reported positive results from the 12 mg dose cohort of the Phase 1b PIONEER trial of pociredir in sickle cell disease, or SCD. Results in 16 patients are as follows: mean absolute absolute mean fetal hemoglobin , or HbF, increased by 8.6% at 12 weeks of treatment with pociredir, representing an increase from a baseline of 7.6% to 16.2%. Seven of 16 patients achieved absolute HbF levels greater than 20% after 12 weeks of treatment with pociredir. HbF levels of 20% are associated with approximately 90% of individual patients experiencing zero vaso-occlusive crises, or VOCs, per year. Proportion of HbF-containing red blood cells increased from a mean of 34% at baseline to 67% at 12 weeks of treatment, consistent with pan-cellular HbF induction evenly distributed across red blood cells. A higher proportion of F-cells is associated with improved red blood cell health. Markers of hemolysis and erythropoiesis improved with pociredir treatment at 12 weeks, indicating a more uniform red blood cell population and healthier bone marrow function. The increase in total hemoglobin indicates that pociredir decreased red blood cell destruction and showed reductions in anemia. A trend of reduced VOC rates was observed during the study period: 8 of 16 patients reported no VOCs during the treatment period; 3 VOCs occurred during the follow-up period as of the June 26, 2025 data cut-off date. The safety profile for pociredir observed in the 12 mg dose cohort was consistent with previously reported safety data.