The FDA in October 2025 granted bitopertin its Commissioner’s National Priority Voucher but after a shortened review time has decided the data did not support regulatory approval for treating erythropoietic protoporphyria.
The FDA has declined to approve Disc Medicine’s bitopertin for a rare disease characterized by extreme, painful sunlight sensitivity, a rejection that comes just months after reports circulated that biologics head Vinay Prasad was skeptical of the drug.
Disc Medicine (stock ticker IRON) closed down about 22% Friday following the news.
“It appears that recent media reports regarding Vinay Prasad’s skepticism of IRON’s bitopertin were well-founded,” analysts at Truist Securities said in a Friday note to investors. The firm called the rejection “surprising,” given that bitopertin met “in our view, all key criteria for accelerated approval.”
In its complete response letter (CRL), which Disc made public through an SEC filing on Friday, the FDA questioned the biotech’s use of a surrogate endpoint—percent change in whole-blood metal-free protoporphyrin IX (PPIX)—as a reasonable predictor of clinical benefit in erythropoietic protoporphyria.
“The percent change in PPIX was relatively modest,” the agency wrote in the CRL, noting that it is uncertain whether such magnitude of biomarker effect “is reasonably likely to predict clinical benefits.” The FDA also noted that some of Disc’s data did not link percent change in PPIX with other endpoints, which in turn “leaves significant uncertainty that bitopertin will have the effect [Disc] purports.”
“It remains somewhat unclear how FDA came to the conclusion that PPIX reduction was not associated with clinical benefit,” BMO Capital Markets wrote on Friday after meeting with Disc management.
For a resubmission, Disc will need to run an adequate and well-controlled study that uses clinical endpoints to measure the efficacy of bitopertin, the FDA said. Nevertheless, the biotech said Friday that the FDA’s concerns are “readily addressable.”
Indeed, Disc is already running the Phase 3 APOLLO study, which aims to enroll 150 patients who have erythropoietic protoporphyria (EPP) or X-linked protoporphyria. While the study will still measure the percent change in whole-blood metal-free PPIX, it will also look at the average monthly time that patients can spend under sunlight without suffering pain from a phototoxic reaction.
The company will request a meeting with the FDA to ensure that APOLLO will be enough to support a resubmission, according to its Friday release. Topline data from the trial are expected by the end of this year.
“While we still remain confident that bitopertin will be able to demonstrate a clear clinical benefit in APOLLO, we recognize the increased risk to approval with FDA now requiring subsequent data from a Ph 3 trial,” BMO said in its note, adding that if all goes well for Disc, an approval could come by “mid-2027.”
Erythropoietic protoporphyria is caused by a certain genetic mutation that, when a person is exposed to sunlight and certain artificial lights, leads to the toxic accumulation of protoporphyrin in the bone marrow, blood plasma and red blood cells. Bitopertin addresses the disease by blocking the glycine transporter 1 protein, which under healthy conditions plays a role in the production of hemoglobin.
In October 2025, bitopertin received the FDA’s Commissioner’s National Priority Voucher, which entitled it to a drastically shortened review period of 1–2 months, down from the typical 10–12 months. A few months later, however, STAT News reported that Vinay Prasad, director of the FDA’s Center for Biologics Evaluation and Research, intervened in bitopertin’s review and was skeptical of the drug’s efficacy.
Given this alleged interference from Prasad, “we feel compelled to call out the eroding credibility of the FDA review process,” BMO wrote in a separate note on Friday. “Lack of consistency with FDA reviews and approvals continues to be a meaningful headwind to the industry which is negatively impacting innovation.”
