FDA Issues Complete Response Letter to Bitopertin For Erythropoietic Protoporphyria

The US Food and Drug Administration (FDA) issued a Complete Response Letter for the New Drug Application (NDA) of Disc Medicine’s bitopertin as a treatment for patients with erythropoietic protoporphyria (EPP).1

The Agency acknowledges sufficient evidence of reduced whole blood metal-free protoporphyrin IX (PPIX) from the AURORA and BEACON trials, but stated a need to see results of the ongoing phase 3 APOLLO study before bitopertin receives approval.1

EPP is a rare, inherited metabolic disorder marked by severe, immediate, and painful photosensitivity, often beginning in childhood. In this patient population, a deficiency in the ferrochelatase enzyme results in protoporphyrin buildup, which is indicated by intense burning, itching, and swelling upon exposure to sunlight.2

Bitopertin is an investigational, clinical-stage, orally administered glycine transporter 1 (GlyT1) inhibitor, designed to modulate heme biosynthesis. GlyT1 is a membrane transporter required to supply sufficient glycine for heme biosynthesis and support erythropoiesis. If approved for EPP, bitopertrin has the potential to be the first disease-modifying therapy.1

“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, JD, PhD, President and Chief Executive Officer of Disc Medicine, in a statement. “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.”1

Bitopertis has been under review for accelerated approval and as part of the Commissioner’s National Priority Voucher pilot program, with accelerated approval contingent on the proposed surrogate endpoint, percent change in whole blood metal-free PPIX, and whether this was reasonably likely to predict a clinical benefit.1

While the FDA agreed that phase 2 double-blind, placebo-controlled AURORA and phase 2 open-label BEACON met the proposed surrogate endpoint, neither showed evidence of an association between percent change in PPIX and sunlight exposure-based endpoints. In turn, the Agency indicated the phase 3 APOLLO results would be needed as evidence for traditional approval.1

APOLLO is a randomized, double-blind, placebo-controlled study evaluating the efficacy, safety, and tolerability of bitopertin in participants with EPP or X-Linked protoporphyria (XLP). Currently, the estimated enrollment size includes 150 participants ≥ 12 years of age.1

Specifically, APOLLO investigators are assessing whether bitopertin increases pain-free sunlight exposure after 6 months of treatment and how PPIX concentration levels change from baseline.1

The trial began enrollment in March 2025, and has an estimated completion timeline of October 2026.1

References

1. Disc Medicine Inc. Disc Medicine Receives Complete Response Letter from FDA for Bitopertin for the Treatment of EPP. GlobeNewswire News Room. Published February 13, 2026. Accessed February 13, 2026. https://www.globenewswire.com/news-release/2026/02/13/3238299/0/en/Disc-Medicine-Receives-Complete-Response-Letter-from-FDA-for-Bitopertin-for-the-Treatment-of-EPP.html

2. Clinicaltrials.gov. Published 2026. Accessed February 13, 2026. https://clinicaltrials.gov/study/NCT06910358