Fulcrum Therapeutics said the U.S. FDA has heightened concerns about the risks and benefits of pociredir, prompting the company to discontinue its sickle cell disease (SCD) development program and begin exploring strategic alternatives. Fulcrum disclosed that FDA feedback referenced a malignancy safety issue observed with another PRC2 inhibitor, Ipsen’s tazemetostat (Tazverik), which Ipsen voluntarily withdrew from the market in March following secondary blood cancer adverse events in the Phase Ib/III SYMPHONY-1 trial. Fulcrum argued pociredir’s target engagement—EED within the PRC2 complex—differs mechanistically from EZH2 inhibition, and it said no new safety signals had emerged in its own pociredir data to date. Even so, FDA concluded that PRC2-complex targeting carries equivalent malignancy risk regardless of the engaged subunit. As Fulcrum ends its sole clinical-stage SCD asset and turns to sale or partnership discussions, the episode underscores how safety signals in one class can rapidly constrain similar epigenetic approaches across hematology programs.