Disc Medicine has announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for the company’s New Drug Application (NDA) for bitopertin as a treatment for patients with Erythropoietic Protoporphyria (EPP), a rare and debilitating hematologic disorder.

In the CRL, the FDA acknowledged that data from the Phase II AURORA and BEACON studies provided sufficient evidence that bitopertin significantly reduces whole blood metal-free protoporphyrin IX (PPIX), a key disease biomarker in EPP. The agency also recognised the strong mechanistic and biological rationale supporting the role of PPIX in the disease.

However, the FDA concluded that the available studies did not demonstrate a clear association between the degree of PPIX reduction and sunlight exposure–based on clinical endpoints as measured in the trials. As a result, the agency indicated that results from the ongoing Phase III APOLLO study would be required to support a potential traditional approval. Topline data from APOLLO are expected in the fourth quarter of 2026.

Bitopertin had been under review for accelerated approval and was also included in the FDA Commissioner’s National Priority Voucher (CNPV) pilot programme. While the FDA agreed that the proposed surrogate endpoint showed biological activity, it determined that confirmatory clinical evidence would be necessary to establish clinical benefit.

Disc Medicine said the issue raised in the CRL is addressable, noting that the APOLLO study is well advanced, with patient enrolment completed in March 2026, several months ahead of schedule. The company plans to request a Type A meeting with the FDA to align on next steps and expects to submit a response to the CRL following completion of the study, with a potential regulatory decision anticipated by mid-2027.

Bitopertin is an investigational, oral glycine transporter 1 (GlyT1) inhibitor designed to modulate heme biosynthesis and is being developed as a potential first disease-modifying therapy for EPP and other hematologic conditions. Disc Medicine holds global rights to the programme under a licensing agreement with Roche.