Disc Medicine received a Complete Response Letter (CRL) from FDA for its New Drug Application (NDA) for bitopertin as a treatment for erythropoietic protoporphyria (EPP), delaying a potential accelerated approval for the investigational therapy.

The company disclosed that bitopertin was submitted under review through the accelerated approval pathway and was named as one of the original drugs apart of the FDA’s Commissioner’s National Priority Voucher pilot program.¹

Disc had previously received a Commissioner’s National Priority Voucher for bitopertin in October 2025 after submitting its application for patients aged 12 years and older under the accelerated approval pathway. The program allows for review timelines of one to two months and offers enhanced agency interaction. Bitopertin has also received Orphan Drug and Rare Pediatric Disease designations.

What is bitopertin?

Bitopertin is an oral inhibitor of glycine transporter 1 (GlyT1), designed to modulate heme biosynthesis.¹ The therapy is currently being developed for EPP, including erythropoietic protoporphyria and X-linked protoporphyria.

The rare genetic conditions are characterized by the accumulation of protoporphyrin IX, a toxic intermediate that triggers severe phototoxic reactions upon sunlight exposure and can lead to hepatobiliary complications in a subset of patients.¹

Why did FDA issue a CRL for bitopertin?

According to Disc, the agency agreed that data from the Phase II Aurora and Beacon studies demonstrated that bitopertin significantly reduced whole blood metal-free protoporphyrin IX, the proposed surrogate biomarker.

However, the FDA concluded that neither trial established an association between percentage reductions in the biomarker and sunlight exposure-based clinical endpoints as measured in the studies.¹ As a result, the agency determined that the evidence was insufficient to support accelerated approval.

The FDA also indicated that results from the ongoing Phase III Apollo study could serve as the basis for traditional approval.

“We are committed to delivering bitopertin to patients, knowing how critical this potentially disease-modifying therapy is to the EPP community. While our efforts at utilizing expedited pathways to get bitopertin to patients quickly have not come to fruition, we are continuing to pursue all avenues in support of FDA approval,” said John Quisel, J.D., Ph.D., President and chief executive officer of Disc Medicine. “The CRL will delay the potential approval of bitopertin, but we have confidence in the ongoing Apollo trial, for which we are seeing incredible enthusiasm from the EPP community. Confidence in our product and program guides our approach, and we will continue working closely with the FDA to support their review.”

What is Disc’s response after receiving the CRL?

Disc says it believes the regulatory issue FDA noted is addressable given that Apollo is already well underway, with topline data expected in the fourth quarter.

A blinded sample size re-estimation conducted in January 2026 did not result in changes to enrollment targets, so the company is expected to complete enrollment in March 2026, earlier than initially planned, citing strong participation from patients and physicians.¹

Following completion of Apollo, Disc intends to submit a response to the CRL and anticipates a potential updated FDA decision by mid-2027.¹ The company reported approximately $791 million in unaudited cash, cash equivalents and marketable securities as of December 31, 2025, and said it maintains a projected cash runway into 2029.

Disc plans to request a Type A meeting with the FDA to discuss next steps, and a copy of the CRL will be filed with the Securities and Exchange Commission.

Bitopertin remains investigational and is not approved in any jurisdiction.

Sources

1. Disc Medicine Receives Complete Response Letter from FDA for Bitopertin for the Treatment of EPP Disc Medicine February 13, 2026 https://ir.discmedicine.com/news-releases/news-release-details/disc-medicine-receives-complete-response-letter-fda-bitopertin
2. Disc Medicine Announces Receipt of FDA Commissioner’s National Priority Voucher (CNPV) for Bitopertin in Erythropoietic Protoporphyria (EPP) Disc Medicine October 16, 2025 https://ir.discmedicine.com/news-releases/news-release-details/disc-medicine-announces-receipt-fda-commissioners-national