The FDA declined to approve Disc Medicine’s bitopertin for erythropoietic protoporphyria (EPP), citing doubts that the drug’s reduction in PPIX (a surrogate biomarker) reliably predicts clinical benefit. The agency’s complete response letter asked for adequate, well-controlled studies using clinical endpoints. Disc received a Commissioner’s National Priority Voucher and had been in a pilot program intended to speed review; nevertheless, the FDA concluded the magnitude of PPIX change was modest and not convincingly linked to patient outcomes. Disc said the agency’s concerns are addressable and pointed to an ongoing Phase 3 APOLLO trial measuring sunlight tolerance as a clinical endpoint. Market reaction was swift: Disc’s stock fell and analysts described the decision as surprising given the accelerated-review context. The FDA’s stance highlights the regulator’s insistence on clinically meaningful endpoints even within expedited pathways, an important precedent for rare-disease sponsors.