The FDA rejected bitopertin in February amid reports of skepticism from former CBER director Vinay Prasad, who has since departed the agency.
Four months after its rare blood disorder drug was rejected by the FDA, Disc Medicine has reached an agreement with the agency to resubmit. The FDA will allow the use of Disc’s current Phase 3 trial, dubbed APOLLO, to support another regulatory filing for bitopertin, the biotech said Tuesday.
This alignment delivers a “noted positive” for Disc, BMO Capital Markets told investors in a Tuesday note, “potentially clearing a path to a full approval submission.” The firm had largely expected the development but nevertheless said it provides “more confidence in the regulatory path for bitopertin.”
If all goes well, the drug could be on track for a mid-2027 decision, BMO said.
It’s been a bumpy regulatory journey for bitopertin to this point. In October last year, the FDA granted the asset a Commissioner’s National Priority Voucher, a ticket that drastically speeds up decision timelines for awardees, shaving review periods down to 1–2 months from the typical 10–12 months. But the faster review did not translate to approval for Disc.
In February, the FDA rejected the company’s application for bitopertin to treat erythropoietic protoporphyria, a rare blood disorder characterized by sensitivity to sunlight and some artificial lights. Patients with this disorder suffer from severe pain once exposed to these light sources. In some cases, erythropoietic protoporphyria is also tied to liver and gallbladder complications.
Bitopertin is an orally available molecule that works by blocking the glycine transporter 1, a protein involved in the production of hemoglobin.
The FDA questioned the adequacy of the surrogate endpoint used by Disc in its Phase 2 trial—percent change in whole-blood metal-free protoporphyrin IX—as a reasonable predictor of clinical benefit.
What made the rejection particularly contentious were reports that Vinay Prasad, former director of the Center for Biologics Evaluation and Research, was skeptical of bitopertin and allegedly interfered in the review process.
A resubmission, the FDA wrote in its rejection letter, would require an adequate and well-controlled Phase 3 trial that measures clinical outcomes, not indicators. APOLLO, as per Disc’s recent meeting with the FDA, ticks these boxes and, if successful, could support full approval for bitopertin. Disc had already launched the Phase 3 APOLLO study at the time of bitopertin’s rejection, though the trial did not make it into the biotech’s original drug application.
This regulatory alignment follows a recent spate of high-level exits at the FDA, including Prasad’s departure at the end of April. He was, for a time, succeeded by his former deputy Katherine Szarama, but she has since been replaced by Karim Mikhail, who had a long career in pharma—including as CEO of Amarin Corporation—before joining the agency last year as a senior advisor.
Former FDA Commissioner Marty Makary has also stepped down, ostensibly ending what Capital Alpha called the “most damaging period in FDA history.” Makary has been temporarily replaced by Kyle Diamantas, the agency’s top food executive.
