Shares of Fulcrum Therapeutics Inc. (NASDAQ: FULC) dropped roughly 20% on Tuesday after the company published 12-week results from the 20 mg dose cohort of its Phase 1b PIONEER study evaluating pociredir in adults with sickle cell disease.
The data set comprised 12 evaluable patients. On average, absolute fetal hemoglobin - HbF - rose by 12.2 percentage points over the 12-week dosing period, increasing from a mean baseline of 7.1% to 19.3% at Week 12. Seven of the 12 patients reached absolute HbF levels of at least 20%, and every patient achieved at least a 6.5 percentage-point absolute increase in HbF.
Fulcrum also reported hematologic and hemolysis marker improvements over the 12 weeks:
- Indirect bilirubin decreased by 40%.
- Lactate dehydrogenase declined by 34%.
- Mean hemoglobin rose by 1.1 g/dL, from a baseline of 7.3 g/dL to 8.4 g/dL.
- The proportion of HbF-containing red blood cells increased from a mean of 31% at baseline to 63% at Week 12.
Clinical event reporting during the active 12-week treatment window recorded six vaso-occlusive crises (VOCs). Seven of the 12 patients experienced zero VOCs during treatment. Fulcrum compared these events to an expected frequency derived from treating physician-documented medical records from the six to 12 months prior to enrollment, noting that approximately 16 VOCs would have been expected during the same treatment period based on those prior records.
Safety observations through the data cutoff date of December 23, 2025 indicated that pociredir was generally well tolerated. The company stated there were no treatment-related serious adverse events and no discontinuations due to treatment-related adverse events. As of that same cutoff, pociredir had been dosed in 148 adults overall, including 89 subjects who had received multiple dose cohorts up to 12 weeks.
Looking ahead, Fulcrum said it will provide further specifics on the design of its next trial in the second quarter of 2026 once it receives the meeting minutes from its End-of-Phase meeting with the U.S. Food and Drug Administration. The company plans to start a potential registration-enabling trial in the second half of 2026.
Contextual note - The market reaction - a roughly 20% decline in the stock on Tuesday - followed the company’s release of the 12-week cohort results.