The FDA issued a complete response letter for Disc Medicine’s bitopertin in erythropoietic protoporphyria (EPP), concluding the surrogate biomarker reductions (PPIX) did not reliably predict clinical benefit. The drug had been selected for a priority review pilot, making the rejection notable given accelerated pathway expectations. The agency asked for an adequate, well‑controlled study using clinical endpoints; Disc said the concerns are addressable and noted an ongoing Phase III APOLLO study that includes clinical sunlight‑exposure endpoints. The CRL spotlights regulatory tension over surrogate endpoints in rare diseases and may prompt sponsors to calibrate endpoint strategies for accelerated pathways.