FDA CRL - Disc Medicine, Inc.

Disc Medicine, Inc. has received a Complete Response Letter (CRL) from the FDA regarding its New Drug Application (NDA 220707) for bitopertin oral tablets. Although clinical trials (Trial 201 and Trial 202) successfully demonstrated that the drug reduces levels of the PPIX biomarker, the FDA determined that the application does not currently meet the standards for approval. The primary issue cited is the uncertainty regarding whether the observed 40% reduction in the PPIX biomarker is sufficient to predict actual clinical benefit for patients. The FDA noted a lack of correlation between the biomarker changes and clinical outcomes, such as sunlight-exposure tolerance, despite the biological plausibility of the treatment. Under the existing regulatory framework, the evidence failed to prove that the drug will have its intended effect under prescribed conditions. To move forward, Disc Medicine must provide evidence from well-controlled trials demonstrating efficacy based on clinical endpoints rather than surrogate biomarkers. The FDA suggested that the company’s ongoing Trial DISC-1459-301 might serve as a path toward traditional approval. Additionally, the company is required to submit a comprehensive safety update covering all clinical and nonclinical trials and must resubmit the application within one year.