Disc Medicine's bitopertin hits all endpoints in Phase 3 EPP trial
Disc Medicine has announced positive topline results from APOLLO, its pivotal Phase 3 trial of bitopertin in erythropoietic protoporphyria (EPP) and the related X-linked protoporphyria (XLP). The Watertown, Massachusetts-based company said the trial met both co-primary endpoints and all secondary endpoints, with exploratory quality-of-life measures also reaching statistical significance.
The double-blind, placebo-controlled trial enrolled 183 adults and adolescents aged 12 or older across the United States, Canada, Europe and Australia. Participants were randomised 1:1 to receive 60 mg oral bitopertin once daily or placebo over six months.
Trial data
On the co-primary endpoints, bitopertin produced a 41.4% reduction in whole-blood metal-free protoporphyrin IX (PPIX) compared with placebo (p less than 0.0001) and increased average monthly total time in light without pain by 12.2 hours in month six versus placebo (p=0.0010). Secondary endpoints, including reduced incidence of phototoxic reactions and increased cumulative time in light over the full six-month period, were also statistically significant. Patient-reported outcome scores, including the Patient Global Impression of Change and Patient Global Impression of Severity measures, likewise favoured bitopertin.
On safety, the company said dizziness was the most common treatment-emergent adverse event in the bitopertin group, reported by 50% of participants, but was described as mild or moderate and generally transient. No adverse events above Grade 3 were recorded and no new safety signals were observed.
Herbert Bonkovsky, Director of Gastroenterology and Internal Medicine at Wake Forest University School of Medicine and a principal investigator of APOLLO, said this was "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."
Regulatory path and market context
Disc said it intends to resubmit a New Drug Application to the US Food and Drug Administration by the end of 2026, with a regulatory decision anticipated by mid-2027. Bitopertin was previously the subject of an earlier NDA cycle; the company did not detail the grounds for that prior submission's outcome in its release, though the new dataset from APOLLO represents a substantially larger and more controlled evidence package.
EPP is a rare, debilitating condition in which mutations in the heme biosynthesis pathway cause toxic accumulation of PPIX. Exposure to sunlight triggers severe pain, oedema and potential blistering, forcing many patients to restrict outdoor activity almost entirely. The sole currently approved therapy in the US is Scenesse (afamelanotide), a surgically implanted synthetic hormone that stimulates melanin production; it addresses light tolerance indirectly rather than targeting the underlying biochemical cause. Bitopertin's mechanism, inhibiting the glycine transporter GlyT1 to reduce heme precursor availability in developing red blood cells, is positioned by Disc as potentially the first disease-modifying approach in EPP.
The rare porphyria space has seen limited therapeutic investment relative to its disease burden, partly because of the small patient population and the complexity of clinical endpoint design. The APOLLO dataset, with robust co-primary and secondary readouts across a multi-continental cohort, should provide regulators with the evidentiary breadth needed for a standard review. Disc obtained global rights to bitopertin from Roche in May 2021, and the drug has been evaluated across multiple earlier trials, including the Phase 2 BEACON and AURORA studies. Full data are expected to be presented at a future medical conference.