The U.S. Food and Drug Administration (FDA) has rejected Disc Medicine’s application for bitopertin, a treatment aimed at patients with erythropoietic protoporphyria, a rare condition that causes severe sensitivity to sunlight. The decision was disclosed in a complete response letter made public by the company on Friday.
Following the announcement, shares of Disc Medicine (IRON) fell by about 22%.
Analysts from Truist Securities commented on the development, stating: “It appears that recent media reports regarding Vinay Prasad’s skepticism of IRON’s bitopertin were well-founded.” They described the FDA’s decision as “surprising,” noting that in their assessment, bitopertin met all major criteria for accelerated approval.
The FDA’s letter questioned whether the use of percent change in whole-blood metal-free protoporphyrin IX (PPIX) could reasonably predict clinical benefit for this patient group. According to the agency: “The percent change in PPIX was relatively modest,” and it remains uncertain if this biomarker effect “is reasonably likely to predict clinical benefits.” The agency also noted gaps between PPIX changes and other clinical endpoints, adding: “[This] leaves significant uncertainty that bitopertin will have the effect [Disc] purports.”
BMO Capital Markets responded after discussions with Disc management: “It remains somewhat unclear how FDA came to the conclusion that PPIX reduction was not associated with clinical benefit.”
For future consideration, the FDA stated that Disc must conduct an adequate and well-controlled study using direct clinical endpoints to measure efficacy. Disc Medicine said Friday that these concerns are “readily addressable.”
Disc is currently running its Phase 3 APOLLO trial, which will include 150 participants with erythropoietic protoporphyria or X-linked protoporphyria. In addition to measuring changes in PPIX levels, this study will track how much time patients can spend outside without experiencing pain from light exposure. The company plans to consult with the FDA to confirm whether data from APOLLO will be sufficient for resubmission. Results from this trial are expected by year-end.
BMO wrote: “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.” They added that approval could come by mid-2027 if results are positive.
Erythropoietic protoporphyria results from genetic mutations causing toxic buildup of protoporphyrin when exposed to sunlight or certain artificial lights. Bitopertin works by blocking glycine transporter 1 protein involved in hemoglobin production.
Bitopertin previously received an FDA Commissioner’s National Priority Voucher in October 2025, which reduced its review timeline substantially. However, reports later surfaced suggesting Vinay Prasad, head of biologics at the FDA’s Center for Biologics Evaluation and Research, expressed doubts about bitopertin's effectiveness during its review process.
BMO addressed these concerns separately: “Given this alleged interference from Prasad, we feel compelled to call out the eroding credibility of the FDA review process,” adding: “Lack of consistency with FDA reviews and approvals continues to be a meaningful headwind to the industry which is negatively impacting innovation.”
The situation reflects ongoing communication challenges at the FDA affecting multiple drug applications across various companies over recent months (source).
