The FDA issued a complete response letter for Disc Medicine’s bitopertin in erythropoietic protoporphyria (EPP), rejecting the submission despite the drug receiving a Commissioner’s National Priority Voucher that had shortened review timelines. The agency questioned whether the surrogate endpoint (percent change in whole‑blood metal‑free protoporphyrin IX, PPIX) reliably predicts clinical benefit, citing uncertainty over magnitude and linkage to patient outcomes. Disc said it believes the agency’s concerns are addressable and highlighted the ongoing Phase III APOLLO study, which includes clinical sunlight exposure endpoints. Analysts described the CRL as unexpected given the expedited pathway and noted it underscores regulatory scrutiny of surrogate endpoints, even under novel review pilots. The CRL raises questions about the voucher pilot’s promise and suggests the FDA will demand robust clinical outcome data rather than rely solely on biomarker shifts in some rare disease contexts.