FDA Issues Complete Response Letter for Disc Medicine's Bitopertin in EPP Treatment

Disc Medicine Inc announced that the U.S. Food and Drug Administration issued a Complete Response Letter (CRL) on February 13, 2026 for the New Drug Application (NDA) 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 (CNPV) pilot program.

Accelerated approval relies on whether there is evidence of an effect on the proposed surrogate endpoint (% 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 President and Chief Executive Officer stated the company is committed to delivering bitopertin to patients, knowing how critical this potentially disease-modifying therapy is to the EPP community. While efforts at utilizing expedited pathways to get bitopertin to patients quickly have not come to fruition, the company is continuing to pursue all avenues in support of FDA approval. The CRL will delay the potential approval of bitopertin, but the company has confidence in the ongoing APOLLO trial, for which it is seeing incredible enthusiasm from the EPP community.

Disc believes the issue raised is readily addressable, given the APOLLO study is already well underway with topline data expected in Q4. Disc plans to request a Type A meeting to review its approach with the FDA. 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. Upon completion of APOLLO, Disc would then file a response to the CRL and expect an updated FDA decision by mid-2027.

Disc has approximately $791 million at December 31, 2025 in unaudited cash, cash equivalents, and marketable securities and maintains guidance of providing runway into 2029. Disc Medicine will host a call for investors at 8 am ET on Tuesday, February 17th to discuss this outcome. A copy of the CRL will be included in a Form 8-K to be filed with the Securities and Exchange Commission.

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 in May 2021. Disc Medicine Inc is a biopharmaceutical company focused on the discovery, development, and commercialization of novel treatments for patients suffering from serious hematologic diseases.