The FDA issued a complete response letter rejecting Disc Medicine’s bitopertin for erythropoietic protoporphyria (EPP), citing uncertainty that the drug’s surrogate biomarker (percent change in whole-blood metal-free PPIX) predicts clinical benefit. The agency asked for an adequate, well‑controlled study using clinical endpoints; Disc said the concerns are addressable and is already running the Phase 3 APOLLO trial that includes sunlight-exposure measures. The files note the regulator flagged modest biomarker effects and incomplete linkage to symptomatic outcomes. Analysts called the decision surprising because bitopertin had been selected for a pilot program to accelerate review. For biotech investors and program teams, the CRL underscores the FDA’s continued insistence on patient-centered clinical endpoints even for rare-disease accelerated pathways.