Disc Medicine's bitopertin meets all Phase 3 goals in EPP after FDA rejection in February

Disc Medicine said on 19 October that its oral drug bitopertin met every primary and secondary objective in a Phase 3 trial in erythropoietic protoporphyria (EPP), a rare disease that makes light painful. The company now intends to resubmit its approval application to the Food and Drug Administration before the end of the year, eight months after the agency turned down an accelerated approval request ¹.

What the trial found

After six months, bitopertin lowered blood levels of protoporphyrin IX (PPIX), the substance that builds up abnormally in EPP, by about 46%. Patients on placebo saw a fall of just over 4% ¹.

The result on light tolerance is the one that matters for the regulator. In the sixth month, patients on the drug gained 12.2 hours of pain-free time in light relative to placebo. Disc also reported improvement on other light tolerance measures, including a steep drop in the painful skin reactions patients experience ¹.

Disc described the drug as well tolerated. Dizziness was the most frequent treatment-related side effect ¹.

Bitopertin blocks GlyT1, a target on developing red blood cells, which is intended to slow the accumulation of toxic PPIX. Disc licensed it from Roche, which had tested it without success in schizophrenia, and repositioned it for EPP ¹.

What it means for the market

The February complete response letter said Disc's earlier trials did not clearly link lower PPIX to greater tolerance of sunlight. The same letter left open a traditional approval if a Phase 3 trial succeeded. The new data address that gap directly, because the trial measured pain-free time in light as well as the biomarker ¹. Leerink Partners analyst Thomas Smith wrote that the findings “substantially” address the FDA's concerns ¹.

The regulatory climate has also moved. Bitopertin was one of the first drugs to receive a national priority review voucher, and the FDA's leadership has since changed. Its newer leaders have reversed several rejections of rare disease drugs and set out plans for a more flexible review framework ¹. For sponsors of rare disease programmes built on surrogate markers, the case shows how a rejection on biomarker evidence can be followed by a second filing backed by a functional outcome.

Competition in EPP is thin but growing. The only marketed therapy is Scenesse, an implant that raises melanin production in the skin. LEO Pharma's dersimelagon could reach approval next year. Bitopertin works by a different mechanism from both and is taken by mouth ¹. Jefferies analyst Roger Song estimated a $1 billion to $2 billion market opportunity and expects broad adoption ¹. Investors reacted quickly: Disc's shares rose by more than 35% on the news ¹.

If approved, bitopertin would be the first marketed drug for Disc, which went public through a reverse merger four years ago ¹.

Caveats

The figures are topline results released by the company. The source gives no trial size, no confidence intervals and no full safety table, and the data have not yet been presented in full or peer reviewed. A potential launch in 2027 depends on the FDA accepting the resubmission, which Disc plans to file by the end of the year ¹.