Fulcrum Therapeutics halted development of its sickle cell disease candidate pociredir and initiated a strategic review after the FDA raised heightened concerns about risks and benefits in the modality class. Fulcrum said FDA feedback followed safety signals linked to a recently withdrawn PRC2 inhibitor, Ipsen’s Tazverik (tazemetostat), from an ongoing Phase Ib/III SYMPHONY-1 trial. The FDA’s concerns centered on an unexpectedly high rate of secondary blood cancers seen in patients exposed to the tazemetostat regimen, which led to Ipsen voluntarily withdrawing Tazverik from the market in March. Fulcrum argued that pociredir’s mechanistic and subunit differences may matter for benefit-risk assessment, but the agency concluded the malignancy risk is equivalent across PRC2 complex targeting. Fulcrum reported that no new safety signals had been observed to date in pociredir, but the agency rejected the possibility of a viable regulatory path forward. The company said it would discontinue the program and consider options including selling the company or assets, while also working to reduce operating expenses. The decision underscores how safety signals from related assets can rapidly constrain the future of precision epigenetic approaches—especially in genetically targeted, chronic conditions like sickle cell disease.