Bitopertin Meets All Endpoints in Phase 3 APOLLO Trial for EPP

Bitopertin, an investigational oral glycine transporter 1 (GlyT1) inhibitor, met both co-primary endpoints and all secondary endpoints in the pivotal phase 3 APOLLO trial in adults and adolescents with erythropoietic protoporphyria (EPP), including X-linked protoporphyria (XLP), according to topline results announced October 19, 2026, by Disc Medicine.¹

The company plans to resubmit a New Drug Application (NDA) to the US Food and Drug Administration (FDA) by the end of 2026, with a decision anticipated by mid-2027. The results arrive 8 months after the FDA issued a complete response letter for bitopertin, which had been under review for accelerated approval based on reductions in whole-blood metal-free protoporphyrin IX (PPIX) in the phase 2 AURORA and BEACON trials.^1,2 The agency indicated APOLLO data would be needed to link PPIX reduction with sunlight-based clinical outcomes.

What Was the Design of the Phase 3 APOLLO Trial?

APOLLO (NCT06910358) was a randomized, double-blind, placebo-controlled trial enrolling 183 patients aged 12 years or older across the United States, Canada, Europe, and Australia.³ Patients were stratified by baseline light tolerance and geography and randomized 1:1 to bitopertin 60 mg or placebo once daily for 6 months.

How Did Bitopertin Perform on PPIX and Time in Light?

Bitopertin reduced whole-blood metal-free PPIX from baseline by 41.4% vs placebo (P < .0001). The second co-primary endpoint, average monthly total time in light without pain during month 6, increased by 12.2 hours vs placebo (P = .0010).

Bitopertin also reduced the incidence rate of phototoxic reactions over the 6-month treatment period (P < .0001) and increased cumulative total time in light without pain over 6 months (P < .0001) vs placebo. Among adults, change from baseline in average daily sunlight exposure time to prodrome favored bitopertin (P = .0077).

Exploratory quality-of-life measures were also statistically significant, with improvements in Patient Global Impression of Change (P < .0001) and Patient Global Impression of Severity (P < .0001) scores vs placebo.

What Was the Safety Profile of Bitopertin in APOLLO?

Bitopertin was generally well tolerated, with no new safety signals observed. Dizziness was the most commonly reported treatment-emergent adverse event in the bitopertin group, occurring in 50% of patients, and was mild or moderate and generally transient.

No treatment-emergent adverse events above grade 3 were reported. Disc Medicine plans to share more detailed APOLLO data at a future medical conference.

Afamelanotide (Scenesse), a surgically implanted melanocortin 1 receptor agonist, remains the only FDA-approved therapy for EPP. Bitopertin instead targets heme biosynthesis upstream to reduce PPIX production.

Editor's Note: This summary has been edited for grammar and clarity using artificial intelligence tools.

References

1. Disc Medicine. Disc Medicine announces success on all primary and secondary endpoints in the pivotal phase 3 APOLLO trial of bitopertin in adults and adolescents with erythropoietic protoporphyria (EPP). News release. October 19, 2026. Accessed October 19, 2026. https://ir.discmedicine.com/news-releases/news-release-details/disc-medicine-announces-success-all-primary-and-secondary.

2. Hillenbrand A. FDA issues complete response letter to bitopertin for erythropoietic protoporphyria. HCPLive. February 13, 2026. https://www.hcplive.com/view/fda-issues-complete-response-letter-bitopertin-erythropoietic-protoporphyria.

3. Study of bitopertin in participants with EPP or XLP (APOLLO). ClinicalTrials.gov identifier: NCT06910358. Accessed October 19, 2026. https://clinicaltrials.gov/study/NCT06910358.