FDA rejects Disc Medicine’s Bitopertin for treatment of Erythropoietic Protoporphyria

The recent issuance of a Complete Response Letter (CRL) by the FDA to Disc Medicine for their New Drug Application (NDA) of bitopertin as a treatment for erythropoietic protoporphyria (EPP) has halted the potential accelerated approval process for this investigational therapy. Bitopertin, an oral GlyT1 inhibitor developed to regulate heme biosynthesis in EPP/X-linked protoporphyria patients, addresses the issue of protoporphyrin IX accumulation, which can lead to photosensitivity and potential liver complications in affected individuals.

The FDA rejected accelerated approval because the Phase II trials did not demonstrate a correlation between reductions in the whole blood metal-free protoporphyrin IX biomarker and clinical benefits associated with sunlight exposure. Therefore, the agency determined that the data did not support granting accelerated approval for bitopertin. Despite this setback, Disc Medicine remains committed to pursuing traditional approval through the Phase III Apollo trial, which is expected to provide the necessary evidence to support regulatory approval. Topline data from the Apollo study are anticipated in Q4, with enrollment completion slated for March 2026 following an unchanged blinded re-estimation.

John Quisel, President, and CEO of Disc Medicine, expressed confidence in the potential of bitopertin as a disease-modifying therapy for the EPP community. While the CRL delays the approval process, the company is optimistic about the ongoing Apollo trial and plans to work closely with the FDA to address the regulatory concerns raised in the rejection letter. Disc plans to submit a response to the CRL after completing the Apollo trial and hopes for a potential updated FDA decision by mid-2027. With approximately $791 million in cash reserves as of December 31, 2025, and a projected cash runway extending into 2029, Disc Medicine is well-positioned to navigate the regulatory process for bitopertin.

Disc Medicine intends to request a Type A meeting with the FDA to discuss the next steps following the receipt of the CRL. Moreover, the company plans to file a copy of the CRL with the Securities and Exchange Commission in line with regulatory requirements. It is important to note that bitopertin remains an investigational drug and has not yet received approval in any jurisdiction.

Despite the setback of the CRL, Disc Medicine remains focused on advancing the development of bitopertin for the treatment of EPP, leveraging the insights gained from the Phase II studies to inform the ongoing Phase III trials. By addressing the regulatory concerns raised by the FDA, Disc aims to bring this promising therapy to patients in need in the coming years.