The FDA-driven reversal of Fulcrum’s SCD program highlighted how class effects in epigenetic modulation can tighten clinical development pathways. Fulcrum’s pociredir discontinuation was explicitly linked to FDA concerns that PRC2 inhibitors may carry comparable malignancy risk across different complex subunits. The decision ties pociredir’s risk–benefit assessment to Ipsen’s tazemetostat withdrawal after secondary blood cancers emerged in SYMPHONY-1. Fulcrum said it raised mechanistic distinctions between EED and EZH2 inhibition, but FDA concluded the hazard extends across the PRC2 complex irrespective of the subunit targeted. Fulcrum indicated it had not observed new safety signals in its program to date and pointed to fetal hemoglobin biology as part of its therapeutic rationale. Still, the FDA’s position blocked a viable regulatory path forward. Strategic review and potential asset sale discussions now reflect how quickly oncology and hematology epigenetic strategies can be reshaped by emerging safety evidence within the same pharmacologic class.