Following a tumultuous stretch under ex-Commissioner Marty Makary, current FDA leadership is working to restore reliability, integrity and transparency to the agency—but experts say that doesn’t necessarily mean an easier regulatory road for drugmakers.
The recent approval of Replimune’s advanced melanoma drug and the FDA’s apparent willingness to work with Capricor to augment the data package for its Duchenne muscular dystrophy cell therapy are signs that the agency has made progress in its bid to restore its reputation of reliability, experts told BioSpace.
But they also say that companies like REGENXBIO and uniQure—both of which walked a challenging regulatory path under former FDA Commissioner Marty Makary and ex-Center for Biologics Evaluation and Research (CBER) chief Vinay Prasad—would do well not to misinterpret the agency’s latest actions as leniency.
Investors had been looking to the recent back-to-back advisory committee meetings for Capricor and Replimune, “as a test of whether the FDA would become meaningfully more permissive under new leadership,” Mizuho Securities analyst Uy Ear told BioSpace in an email interview. Instead, the outcomes suggest that “regulatory decisions remain highly data-driven,” he said.
This is a crucial indicator for companies like uniQure, REGENXBIO and Disc Medicine—as well as others that had previously been spurned by the agency and which are banking on some degree of regulatory flexibility as they prepare to submit or resubmit their applications, Ear said.
“I think the key lesson is to minimize areas open to interpretation,” he continued. “Companies should align with the FDA early and proactively address potential questions . . . well in advance of an FDA review or AdCom.”
Donald Fink, a former FDA employee who worked at CBER, offered similar advice, telling BioSpace in an email that companies should adhere “to the extent reasonable” to the guidance and recommendations set by the FDA throughout the course of their product development.
That advice might be difficult to swallow for Capricor, however, which weathered a frustrating advisory committee meeting late last month and now must contend with a possible review delay for its lead asset, deramiocel.
Confusion and chaos
Last month, the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) voted 9–3 against the approval of deramiocel, with some experts calling the pivotal data presented by Capricor “very fragile.” The meeting and the FDA briefing documents that preceded it came as a surprise to CEO Linda Marbán, who was under the impression that Capricor had the agency’s support for its statistical analysis plans.
Parts of the FDA’s briefing documents “were so hard to reconcile with what actually occurred,” Marbán told the committee on July 29.
The adcomm was marred by disagreement between the FDA and Capricor over which statistical analysis plan to review and even which endpoint to focus on.
This confusion is not new. Under Makary’s leadership, the FDA endured what analysts at Capital Alpha called “the most damaging period in FDA history.” Certainly, Makary oversaw massive staff cuts and contentious decisions—a July 2025 rejection for Capricor among them, alongside the refusal to review Moderna’s mRNA flu vaccine earlier this year and other apparent reversals of guidance.
Makary left the agency in May, just two weeks after Prasad, arguably his most controversial lieutenant, who oversaw many of the agency’s most disputed decisions.
Replimune’s advanced melanoma therapy Tudriqev—previously known as RP1—was one. Before coming away with an accelerated approval earlier this month, the drug was rejected twice, most recently in April.
In the post-Makary and Prasad era, things began to change for several biotechs, including Replimune. RP1 was accepted for re-review—and this time was put through its own uphill adcomm battle. It didn’t look good. Ahead of a CTGTAC meeting in late July, the FDA in briefing documents said Replimune’s submission was “not interpretable.”
The panel of independent experts largely agreed with the FDA on this point, with one even calling the data “messy”, but nevertheless voted 10–3 in support of an approval.
Return to reliability
Meanwhile, Capricor’s regulatory road continues. On August 13 during the biotech’s second quarter earnings call, Marbán said the FDA is receptive to open-label extension data being added to the current submission—a move that would necessitate an extension of deramiocel’s current Aug. 22 PDUFA date.
As the industry waits for this process to play out, the FDA appears to be “quickly acting to put its immediate predecessors—namely Makary and Prasad—in the rear-view mirror,” said Fink.
What that means is a conscious effort from the agency to return to reliability and transparency—and the recent Capricor and Replimune adcomms are the clearest examples of that, Fink added.
Such independent scrutiny is also a distinct possibility for uniQure, which is preparing to submit an application in the third quarter for its Huntington’s disease gene therapy AMT-130—previously maligned by both Makary and Prasad. In fact, the biotech is eager for the opportunity to face an expert panel.
“We welcome it,” Chief Medical Officer Walid Abi-Saab told investors during uniQure’s second quarter earnings call last month. CEO Matt Kapusta agreed, pointing to “constructive and productive” recent interactions with the FDA. “Our view is that the data speaks for itself and we would very much look forward to . . . participating and having that discussion,” he said.
UniQure’s confidence comes from AMT-130’s strong clinical profile. Phase 1/2 data released in September last year showed that the asset significantly slowed disease progression after three years. Just a couple of months later, however, the FDA said the data wasn’t enough to support an application for accelerated approval—despite having previously agreed to uniQure’s development plan.
The FDA again backtracked in June, saying that data from the Phase 1/2 study would be sufficient to support an application for AMT-130 under its accelerated approval pathway. As of publication, no adcomm had been scheduled for AMT130.
Many other companies have also been given a new regulatory lease. Disc Medicine, for instance, has reached an agreement with the FDA for a resubmission for its rare disease drug bitopertin, which was rejected in February amid reports of Prasad’s skepticism.
REGENXBIO is also looking to resubmit after a Makary-era rejection for its Duchenne muscular dystrophy gene therapy. The FDA in June said it would no longer look for another study or a new control arm—a reversal from concerns raised in the rejection letter.
For these drugmakers, Fink warned against complacency. “Caution is recommended against over exuberance with respect to the self-assessed sufficiency of clinical data to demonstrate clinical effectiveness,” he said.
Just because companies have had “productive” meetings with the FDA doesn’t mean they’ll get a favorable outcome, Fink continued. “Agreements reached about study design and the sufficiency of clinical data collected to support a licensing application does not ensure the outcome of a BLA review will be regulatory approval.”
In this context, the best thing drugmakers can do is to ensure that their application packages are as airtight as possible, minimizing points of contention and preparing robust answers to potential regulatory questions even before they’re asked, Mizuho’s Ear recommended.
“FDA reconsiderations are likely to remain highly case-specific,” he added, “with outcomes driven by the particulars of each dataset and the regulatory questions at issue.” This is true not only for the FDA’s final verdict, but also for adcomm meetings, he continued, with different panels including a different makeup of advisors.
Despite adding another hoop that biotechs must jump through to obtain approval, experts consulted by BioSpace agree that the return of these adcomms is an unqualified positive for the industry—a step toward regaining some of the reliability and trust that was lost under Makary.
“Advisory committees have long been central to public and stakeholder acceptance of FDA’s decisions, notably on tough safety, efficacy, and risk-benefit questions,” Steven Grossman, president of policy and regulatory consulting firm HPS Group, told BioSpace via email.
Regardless of what the regulator’s ultimate verdict is, “what matters is that each product received an expert, transparent, and fair discussion in a public forum,” he added. “No one has to guess what went into FDA’s thinking.”
