Disc Medicine is moving forward with plans to address the U.S. Food and Drug Administration’s (FDA) rejection of its rare disease therapy, bitopertin. The company aims to respond to the agency’s complete response letter (CRL) by completing a new Phase 3 trial called Apollo, which tests bitopertin in patients with erythropoietic protoporphyria, a condition causing pain upon sunlight exposure.
On a recent call with analysts, CEO John Quisel expressed confidence in the strategy, stating that enrollment for the Apollo trial is ongoing and expected to finish by March, ahead of schedule. He noted that topline data should be available by year-end and said Disc plans to refile its application soon after, possibly leading to an FDA decision by mid-2027.
However, some analysts raised concerns about whether current FDA leadership will honor agreements made under previous leadership. The protocol for the late-stage trial was developed in 2024 during the Biden administration. Since then, much of the agency’s leadership has changed under President Donald Trump’s administration. New appointees have issued several surprise rejections, including a recent refusal to review Moderna’s mRNA-based flu vaccine due to issues with trial design—even though the FDA had previously approved that protocol.
This broader pattern of regulatory unpredictability at the FDA has affected other companies as well. Over the past nine months, firms such as Sarepta, Capricor, and uniQure have also experienced unexpected setbacks from the agency. Some industry observers argue this trend points to ongoing communication challenges within the FDA review process.
The Apollo study will compare bitopertin against placebo on two main measures: how long patients can spend in light without pain each month and changes in whole-blood metal-free protoporphyrin IX (PPIX), a biomarker seen as indicative of clinical benefit for this 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 during 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.”
Quisel emphasized that Disc will have opportunities for further discussions with regulators before submitting its response to the CRL. This includes a Type A meeting regarding the rejection itself. He pointed out that language in the CRL indicated more evidence from a study like Apollo would be necessary.
“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.
Following news of these developments and despite earlier declines after rejection news broke, Disc shares rose 9% on Tuesday morning but remained below last week’s levels.
Quisel acknowledged disappointment over not achieving approval after earlier signals from meetings suggested smooth progress through regulatory channels. Bitopertin had received both accelerated review status and was granted a Commissioner’s National Priority Voucher—a program initiated by Commissioner Marty Makary intended for drugs addressing critical unmet needs requiring rapid assessment.
“There was ‘a rich record of the FDA aligning with us on this as the appropriate path for review,’” Quisel added. However, he noted that additional regulators involved later in reviews may apply different standards or perspectives: “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.”
Reports surfaced last December indicating Center for Biologics Evaluation and Research chief Vinay Prasad became personally involved in reviewing Disc's application.
In response to Disc's February 13 rejection—one among several recent high-profile denials—BMO Capital Markets commented: “we feel compelled to call out the eroding credibility of the FDA review process.”
