Disc Medicine Posts Phase 3 Bitopertin Win In EPP, Reopening Its FDA Path After Last Year’s Rejection

Disc Medicine has produced the clinical result it needed to get bitopertin back in front of the FDA. In the Phase 3 APOLLO trial, the company said the drug met both co-primary endpoints and all secondary endpoints in erythropoietic protoporphyria, or EPP, a rare blood disorder that causes painful sensitivity to sunlight.

That outcome resets a program that was turned away last year when an accelerated application was rejected. The earlier complete response letter, disclosed in a February 13 SEC filing by Disc, questioned whether percent change in whole-blood metal-free protoporphyrin IX, or PPIX, was a reasonable predictor of clinical benefit in EPP. APOLLO now gives Disc clinical outcome data to pair with the biomarker effect, which changes the regulatory posture from a surrogate-endpoint debate to a traditional approval package built on direct patient benefit.

The data

APOLLO enrolled 183 adults and adolescents with EPP. Disc said bitopertin reduced PPIX by 41.4% versus placebo, with a p-value of less than 0.0001, and increased time patients were able to spend in the light by 12.2 hours during month six, with a p-value of 0.0010. Those were the study’s two co-primary endpoints.

Disc also said all secondary endpoints were positive, including a statistically significant reduction in phototoxic reactions and increased light tolerance. Exploratory quality-of-life measures were also statistically significant.

On safety, the company said bitopertin was generally well tolerated and that no new safety signals were observed. Dizziness was the most common treatment-emergent adverse event, reported in 50% of patients in the treatment group, but Disc said those cases were mild to moderate and generally transient. The company also said there were no study discontinuations in the bitopertin arm during the six-month study.

The result is important because EPP trials need to show a tangible improvement in daily function, not only movement in a biomarker. BMO Capital Markets senior biopharma analyst Evan Seigerman told BioSpace before the readout that if APOLLO hit its sunlight-exposure endpoint, there was a real path forward for approval.

The road here

The FDA’s prior objection was narrow but consequential. In the complete response letter, the agency wrote that the percent change in PPIX was relatively modest and that it was unknown whether that magnitude of biomarker effect was reasonably likely to predict clinical benefit.

Disc disclosed in June that it had reached agreement with the FDA that the ongoing APOLLO trial, if successful, could support another regulatory filing for bitopertin. After Monday’s data, the company said it plans to resubmit by the end of the year, this time seeking traditional approval.

Bitopertin also carries one procedural advantage. It was one of the first recipients of the Commissioner’s National Priority Voucher in October 2025. According to the source, that voucher can shorten review to one to two months from the typical 10 to 12 months, though it does not guarantee approval.

When Disc returns to the agency, it will do so before an FDA that the source says looks different than it did in February. Former Commissioner Marty Makary, Center for Biologics Evaluation and Research director Vinay Prasad and Center for Drug Evaluation and Research Acting Director Tracy Beth Høeg have all departed the agency. The source also reported that Prasad intervened in the initial review and expressed skepticism about the drug’s efficacy.

Competitive context

If approved, bitopertin would enter a market with one existing treatment named in the source: Clinuvel Pharmaceuticals’ Scenesse, a subcutaneous implant approved for EPP and to prevent phototoxic reactions. That means Disc is no longer arguing only for regulatory acceptance of a biomarker; it is trying to establish a second treatment option with evidence on light exposure, phototoxic reactions and quality of life.

The signal from APOLLO is that rare-disease regulators may still reject accelerated cases built on biomarker logic when the clinical link looks uncertain, but a later success can be enough to reopen the file if the confirmatory study is designed around direct functional benefit.