FDA Denies Accelerated Approval for Bitopertin in EPP, Awaits Phase 3 Trial Results

The U.S. Food and Drug Administration issued a Complete Response Letter on February 13, 2026, for the New Drug Application for bitopertin as a treatment for patients with erythropoietic protoporphyria (EPP). Bitopertin had been under review for accelerated approval and as part of the Commissioner's National Priority Voucher pilot program.

Accelerated approval relies on whether there is evidence of an effect on the proposed surrogate endpoint (percent change in whole blood metal-free PPIX) and whether the proposed surrogate endpoint, including the magnitude of change, is reasonably likely to predict a clinical benefit. On the first point, the FDA agreed that AURORA and BEACON provided sufficient evidence that bitopertin significantly lowers whole blood metal-free PPIX. On the second, based on review of AURORA and BEACON results, the FDA concluded that the trials did not show evidence of association between percent change in PPIX and sunlight exposure-based endpoints, as measured in the trials, despite the strong mechanistic and biological plausibility supporting the use of the PPIX biomarker in protoporphyria.

The FDA indicated results of the APOLLO study could serve as evidence to support traditional approval. The APOLLO study is a randomized, double-blind, placebo-controlled trial evaluating the efficacy, safety, and tolerability of bitopertin in participants with EPP or X-Linked protoporphyria. The study is comparing six months of treatment with bitopertin against a placebo, with the main goals of evaluating the therapy's safety, its effect on PPIX levels, and the amount of pain-free time patients can spend in the sun. The trial is recruiting patients 12 and older with EPP or X-linked protoporphyria at sites across Europe, the U.S., Australia, and Canada.

A blinded sample size re-estimation of the APOLLO study was conducted in January and no modifications to sample size were needed based on statistical analysis. There has been significant patient and physician enthusiasm around the APOLLO trial, allowing Disc to complete trial enrollment in March 2026, several months earlier than expected. Topline data are anticipated in Q4 2026.

The company plans to request a Type A meeting to review its approach with the FDA. Upon completion of APOLLO, Disc would then file a response to the CRL and expect an updated FDA decision by mid-2027.

Bitopertin is an investigational, clinical-stage, orally administered inhibitor of glycine transporter 1 (GlyT1) that is designed to modulate heme biosynthesis. GlyT1 is a membrane transporter expressed on developing red blood cells and is required to supply sufficient glycine for heme biosynthesis and support erythropoiesis. Disc is developing bitopertin as a potential treatment for a range of hematologic diseases including erythropoietic porphyrias, where it has potential to be the first disease-modifying therapy.

Bitopertin has been studied in multiple clinical trials in patients with EPP, including the Phase 2 open-label BEACON trial, the Phase 2 double-blind, placebo-controlled AURORA trial, an open-label extension HELIOS trial, and the confirmatory Phase 3 double-blind, placebo-controlled APOLLO trial. Bitopertin is an investigational agent and is not approved for use as a therapy in any jurisdiction worldwide. Disc obtained global rights to bitopertin under a license agreement from Roche in May 2021.

EPP is a rare, inherited metabolic disorder marked by severe, immediate, and painful photosensitivity, often beginning in childhood. In this patient population, a deficiency in the ferrochelatase enzyme results in protoporphyrin buildup, which is indicated by intense burning, itching, and swelling upon exposure to sunlight.

Disc Medicine has approximately $791 million at December 31, 2025 in unaudited cash, cash equivalents, and marketable securities and maintains guidance of providing runway into 2029. The company will host a call for investors at 8 am ET on Tuesday, February 17th to discuss this outcome.