FDA Rejects Disc Medicine’s EPP Drug

Rare Daily Staff

The U.S. Food and Drug Administration told Disc Medicine it would not approve its application to market its experimental therapy bitopertin to treat erythropoietic protoporphyria, a rare blood condition.

The decision delays a potential approval that had been under accelerated review as part of the FDA commissioner’s National Priority Voucher pilot program.

Erythropoietic protoporphyria, or EPP, is a rare, inherited disease in which toxic molecules called protoporphyrins build up in red blood cells and other tissues, causing severe pain and skin reactions after even brief exposure to sunlight. This protoporphyrin accumulation can lead to liver, gallbladder, or bile duct complications in a subset of patients, and it is a serious, lifelong hematologic and metabolic condition.

Bitopertin is an oral inhibitor of glycine transporter 1, or GlyT1, designed to modulate heme biosynthesis. Disc licensed global rights to the candidate from Roche in 2021, and it is developing the drug as a potential first disease-modifying therapy for EPP and related hematologic conditions.

The agency acknowledged that data from Disc’s phase 2 AURORA and BEACON trials showed bitopertin significantly reduced levels of protoporphyrin IX, or PPIX, a key biomarker in EPP. Regulators also said there was strong mechanistic and biological support for using PPIX reduction as a surrogate endpoint for clinical benefit.

However, the agency concluded that the trials did not demonstrate a clear link between decreases in PPIX and improvements in light-tolerance measures, which served as the clinical endpoints in those studies. As a result, the FDA said it wants to see results from the ongoing phase 3 APOLLO study before reconsidering approval.

The phase 3 APOLLO trial is designed to confirm the clinical benefit of bitopertin in EPP. Top-line data are expected in the fourth quarter of 2026, and Disc said results could form the basis for traditional approval. The company plans to request a Type A meeting with the FDA to discuss next steps, and it intends to respond to the complete response letter after the APOLLO results are available.

“We are committed to delivering bitopertin to patients, knowing how critical this potentially disease-modifying therapy is to the EPP community,” said John Quisel, president and CEO of Disc. “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.”

Photo: John Quisel, president and CEO of Disc Medicine