Disc Medicine’s leadership tried to express optimism that its rare disease therapy bitopertin can be approved based on a Phase 3 trial set to begin shortly. However, analysts are worried that the protocol was developed with former FDA leaders.
Disc Medicine has a clinical plan to come back from the FDA’s surprise rejection of the rare disease therapy bitopertin. The problem is, the version of the agency that cleared the Phase 3 trial that’s part of that plan is long gone.
CEO John Quisel projected confidence on a Tuesday call with analysts as he talked about the company’s next steps following the FDA’s rejection of bitopertin for erythropoietic protoporphyria. Disc believes that the agency’s complete response letter (CRL) is “addressable” by the planned Phase 3 Apollo study.
Enrollment in the trial is ongoing and expected to be complete in March, sooner than expected, with topline data to follow by the end of the year, Quisel explained. Disc will then refile with the FDA, meaning a potential decision could arrive by mid-2027.
The problem, analysts pointed out, is that Disc developed the late-stage trial protocol with the FDA in 2024 under the Biden administration. Nearly the entire leadership team that existed then is long gone, and the new regulators—appointed by or hired under President Donald Trump—have been tossing out surprise rejections left and right. This includes last week’s refusal to even review Moderna’s mRNA-based flu vaccine due to inadequate trial design, despite the FDA having signed off on the protocol.
So, analysts want to know: Will the new regulators agree to the old protocol? And if they don’t, will they let Disc know before that mid-2027 decision?
The Apollo trial will test bitopertin against placebo in patients with erythropoietic protoporphyria, a rare metabolic disorder that causes pain with exposure to sunlight. In the Phase 3 trial, Disc is looking to show improvement on two co-primary endpoints: the average monthly time in light without pain and change in whole-blood metal-free protoporphyrin IX (PPIX), a biomarker that is considered a reasonable predictor of clinical benefit in the disease.
“Maybe I just need to be a little clearer, because I hear everyone asking, like, ‘Oh, is there an issue? Is the FDA going to change their view on the Apollo trial?’” Quisel said on the call. “I feel like I can lean in pretty hard on that and say there’s just absolutely no evidence of that right now.”
Disc will have several opportunities to discuss things with the FDA before the CRL response is filed, including during a Type A meeting about the rejection itself, the CEO stressed. Quisel also highlighted the text of the CRL, which suggested the Apollo trial is needed to add more evidence.
“I feel like the CRL is essentially pointing to the Apollo trial as designed as being the path to getting the data set that they would view as appropriate for supporting approval,” Quisel said.
After declining in the wake of the FDA rejection, Disc’s shares rose 9% to $60.94 on Tuesday morning. However, the bump was not enough to erase the previous five days’ loss of 17%.
The Arc of Rejection
The disappointment from Quisel, even as he sought to project an optimistic tone, was obvious. After reviewing Disc’s bitopertin application, the FDA “reached a different conclusion than expected, which certainly creates a lot of whiplash for everyone,” the CEO said. “Sorry we couldn’t achieve a better result. We’re going to keep working on this, and hopefully we have great data as we come in towards the end of the year.”
He acknowledged that the company had been expecting a different outcome with the FDA after earlier meetings suggested the application was moving through the regulatory process smoothly. Bitopertin was even granted a Commissioner’s National Priority Voucher, a new initiative of Commissioner Marty Makary that selects drugs that meet certain national priorities or address a critical unmet need for an extremely quick review process.
The drug application had also been reviewed under the accelerated review timeline. Quisel said there was “a rich record of the FDA aligning with us on this as the appropriate path for review.”
He added that as a drug inches toward approval, a broader set of regulators get involved who can have different perspectives and standards.
“I guess what we see here is a different standard that arose controlling the outcome. . . . That’s how we see the arc of what went on here, although, to be honest, we don’t actually have a tremendous amount of information from the review process at this point,” Quisel said.
Reports emerged in December 2025 that Center for Biologics Evaluation and Research chief Vinay Prasad had personally become involved in the application.
In the aftermath of Disc’s Feb. 13 rejection—one of many that have sent shockwaves through the industry—BMO Capital Markets stated in a note to investors: “we feel compelled to call out the eroding credibility of the FDA review process.”
