Key Information
A high dose of pociredir, Fulcrum Therapeuticsexternal link, opens in a new tab’ oral drug candidate for sickle cell diseaseexternal link, opens in a new tab (SCD), boosted fetal hemoglobin (HbF) levels and reduced red blood cell destruction — thereby easing symptoms of anemia — in a small group of patients with the blood disorder.
These are the latest results from the Phase 1b PIONEER clinical trial (NCT05169580)external link, opens in a new tab, which is evaluating up to five daily doses of pociredirexternal link, opens in a new tab over 12 weeks, or about three months, in adults with severe SCD. The new analysis centers on the 12 participants who finished the entire 12-week course at the highest dose studied to date, 20 mg.
“The 12-week data from the complete 20 mg [patient group] demonstrated robust and rapid HbF induction … accompanied by reductions in markers of hemolysis [red blood cell destruction] and associated improvements in anemia,” Alex C. Sapir, Fulcrum’s president and CEO, said in a company press releaseexternal link, opens in a new tab detailing the findings.
“These encouraging results in a severe patient population strengthen our conviction as we prepare for discussions with regulators regarding the design of the next study,” Sapir said.
Fulcrum plans to launch a potential registration-enabling trial — one designed to generate high-quality safety and efficacy data that, if positive, will support an application for the therapy’s approval — in the second half of this year. Additional details about the trial’s design are expected by the end of June.
The company also plans to meet mid-year with the European Medicines Agency, which evaluates and monitors drug treatments in the European Union, to request protocol assistance and obtain feedback on the proposed trial design.
SCD results from genetic mutationsexternal link, opens in a new tab that lead to an abnormal form of adult hemoglobin, the protein that transports oxygen in red blood cells. It tends to stick together, distorting red blood cells into a sickle-like shape. This makes the cells prone to destruction, resulting in anemia, or low levels of healthy red blood cells, and blocking blood flow in small blood vessels. That leads to painful vaso-occlusive crisesexternal link, opens in a new tab (VOCs), the most common cause of hospitalization related to SCD.
HbF is the version of hemoglobin made before birth. After birth, HbF production gradually declines while adult hemoglobin increases. This transition is partly regulated by the BCL11A protein, which reduces HbF production.
Pociredir aims to boost production of fetal hemoglobin
Formerly known as FTX-6058external link, opens in a new tab, pociredir works by lowering BCL11A levels, thereby boosting HbF production. It aims to reduce VOCs and relieve other SCD symptomsexternal link, opens in a new tab.
Early PIONEER data showed that 12 weeks of pociredir at the 12 mg dose were well toleratedexternal link, opens in a new tab and increased HbF levels, as well as the proportion of F-cells, the red blood cells that produce HbF.
The 20 mg dose group completed enrollment last October, and preliminary results, covering at least six weeks of treatment, were similarexternal link, opens in a new tab to those of the 12 mg dose group.
As of late last year, all 12 evaluable patients in the 20 mg group had completed the 12-week treatment period. Data showed their mean HbF level rose by 12.2%, from a pretreatment value of 7.1% to 19.3% after 12 weeks. By comparison, patients in the 12 mg group previously showed an 8.6% increase at the same time point.