Bitopertin Meets All End Points in Phase 3 APOLLO Trial for EPP

Disc Medicine recently announced topline results from the phase 3 APOLLO trial of bitopertin in erythropoietic protoporphyria (EPP), including X-linked protoporphyria (XLP). According to the company, bitopertin met both co-primary end points and all secondary end points vs placebo. Disc plans to resubmit a New Drug Application (NDA) to the FDA by the end of 2026, with a decision anticipated by mid-2027.¹

Bitopertin is an investigational, orally administered inhibitor of glycine transporter 1 (GlyT1) designed to modulate heme biosynthesis. Scenesse (afamelanotide), a surgically implanted synthetic hormone, remains the only FDA-approved therapy for EPP. Disc obtained global rights to bitopertin from Roche in May 2021 and previously studied the agent in the phase 2 BEACON and AURORA trials and the open-label extension HELIOS trial.¹

“The success of the small molecule glycine transporter 1 inhibitor bitopertin in its phase 3 clinical trial program across all primary and secondary end points is a major step forward for EPP and XLP patients suffering from toxic buildup of protoporphyrin IX. Bitopertin targets the biochemical problem in EPP/XLP, reducing the heme biosynthesis pathway production of PPIX which is responsible for painful phototoxicity and, for some patients, hepatotoxicity,” said Christopher Bunick, MD, PhD, dermatologist, associate professor of dermatology at Yale School of Medicine, and editor in chief of Dermatology Times, in an exclusive statement.

APOLLO is a randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of bitopertin in adults and adolescents aged 12 years or older with EPP or XLP (NCT06910358).¹˒² The trial enrolled 183 patients across the US, Canada, Europe, and Australia. Patients were stratified by baseline light tolerance and geography and randomized 1:1 to receive 60 mg of oral bitopertin or placebo once daily for 6 months.¹

Bitopertin achieved statistical significance on both co-primary end points. Whole-blood metal-free protoporphyrin IX (PPIX) decreased by 41.4% from baseline vs placebo (P < .0001). Average monthly total time in light without pain during month 6 increased by 12.2 hours vs placebo (P = .0010).¹

Disc stated more detailed data will be shared at a future medical conference. Responder counts and absolute baseline values were not included in the topline announcement.¹

Bitopertin Secondary End Points and Safety Profile in APOLLO

Bitopertin achieved statistical significance on all secondary end points vs placebo. The incidence rate of phototoxic reactions over the 6-month treatment period decreased (P < .0001), and cumulative total time in light without pain over the same period increased (P < .0001). Change from baseline in average daily sunlight exposure time to prodrome also improved (P = .0077), although this analysis was limited to adults.¹

Exploratory end points of quality of life also reached statistical significance. Patient Global Impression of Change (PGIC) scores improved vs placebo (P < .0001), as did Patient Global Impression of Severity (PGIS) scores (P < .0001).¹

Disc described bitopertin as generally well tolerated and reported no new safety signals. Consistent with prior studies, dizziness was the most commonly reported treatment-emergent adverse event (TEAE) in the bitopertin group, occurring in 50% of patients. Events were mild or moderate and generally transient, and no TEAEs exceeded grade 3.¹

Herbert L. Bonkovsky, MD, director of gastroenterology & internal medicine and professor emeritus of medicine at Wake Forest University School of Medicine, and a principal investigator of APOLLO, said in the news release, “This is the first time a potential treatment for EPP has shown robust evidence of whole blood PPIX reduction alongside unequivocal improvement on important measures of disease severity: increased time in light, reduced phototoxic reactions, and improved Patient Reported Outcome scores.”¹

Disc describes bitopertin as having the potential to be the first disease-modifying therapy for EPP, based on a mechanism aimed at reducing PPIX production. The company also plans to develop the agent for a range of hematologic diseases, including erythropoietic porphyrias. Bitopertin is not approved for use in any jurisdiction worldwide.¹

“The ability for bitopertin to increase patient time in light without pain and reduce phototoxic reactions suggests it can meaningfully improve the quality of life of EPP/XLP patients,” Bunick concluded.

References

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