Through flux and fluidity, FDA keeps coming back to rare disease
July 8, 2026 |
6 min read |
Heather McKenzie
Even as FDA approvals for biologic therapies fell in the first half of 2026, regulatory experts are optimistic about a turnaround in the rare disease space after the departure of key leaders at the agency. Still, there will continue to be tension between science and politics
The FDA approved six orphan drugs in the first half of 2026—leaving the agency just six months to match last year’s total of 30
The Center for Biologics Evaluation and Research (CBER)—which regulates gene therapies and therefore many rare disease drugs—approved two orphan drugs in H1, Rocket Pharmaceuticals’ Kresladi for the rare immune disease leukocyte adhesion deficiency-I and Regeneron Pharmaceuticals’ Otarmeni for a genetic form of hearing loss. This compares to between three and nine first-half CBER approvals between 2020 and 2025, according to a Sunday report from Jefferies. The Center for Drug Evaluation and Research (CDER) approved four additional novel rare disease drugs in the first half of 2026, per BioSpace analysis.
For Peter Pitts, who previously served as FDA associate commissioner, regulatory action around rare disease drugs in 2026 can be divided into two phases—the first four months of the year under former CBER Director Vinay Prasad and the past eight weeks. “I think with Dr. Prasad’s departure, FDA has returned to its senses as being a partner in innovation rather than a critic of innovation,” Pitts told BioSpace
The FDA’s regulation of rare disease drugs has been perhaps its biggest point of contention with drug companies over the past 18 months—thanks, in large part, to Prasad. Companies like Capricor Therapeutics, uniQure, Biohaven and others were sent on a regulatory—and market—rollercoaster ride as the agency dramatically reversed course after having previously signed off on their registrational studies
But two months ago, the tide began to turn. Prasad left the agency at the end of April, with former FDA Commissioner Marty Makary following him out the door in the middle of May. Acting Commissioner Kyle Diamantas met with rare disease groups at the beginning of June seeking to “repair relations with a sector disappointed by his predecessor,” according to reporting by Reuters
Pitts had a different perspective on the meeting’s purpose, however. “I don’t think it’s a question of mending fences,” he said, adding that no one is singing “kumbaya.”
“I think what this indicates is the FDA’s willingness to recognize that sponsors have an equal voice in the process and need to be listened to rather than dictated to,” he continued
Whatever the reason, the regulatory space for rare disease therapies appears to have cleared, with multiple decisions—and advisory committees—scheduled for the second half of this year, including some whose rejections under Makary and Prasad sparked controversy
Last month, Disc Medicine announced it had reached an agreement with the FDA to resubmit for approval of its rare blood disease drug bitopertin—which was rejected in February following criticism from Prasad—supported by the company’s current Phase 3 trial. The agency also did a 180 on uniQure’s Huntington’s disease gene therapy, agreeing that three-year data from the company’s Phase 1/2 trial could support an application for accelerated approval and that a sham-surgery controlled Phase 3 trial may not be necessary, as Makary and Prasad had insisted. Replimune and Saol Therapeutics have each resubmitted rejected therapies after further discussions with the FDA, and REGENXBIO has announced plans to do the same.
Rare disease has been a priority for the FDA since the Orphan Drug Act of 1983, Amy Comstock Rick, associate director for Rare Disease Strategy and director of Strategic Coalitions at CDER’s Rare Disease Innovation Hub, told BioSpace on the sidelines of BIO 2026. But with the MAHA report’s emphasis on common, chronic diseases, “rare may not have had the level of prioritization they’ve had before,” she added. “I think in the last six weeks that’s been brought back a little bit.”
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H2 2026 and beyond
The FDA still has a long way to go to match last year’s number of 30 orphan disease approvals
In 2025, rare disease medicines accounted for exactly half of CDER’s nods, with that number at slightly more than half for CBER, Rick said. CBER granted five approvals for novel orphan drugs in 2025
These included Stealth BioTherapeutics’ Forzinity, the first-ever treatment for Barth syndrome, Johnson & Johnson’s Imaavy for generalized myasthenia gravis and Crinetics’ Palsonify for the rare pituitary condition acromegaly. Crinetics—and Palsonify—were snapped up by Vertex Pharmaceuticals on Tuesday for $10 billion in one of 2026’s largest deals to date
The FDA’s H1 2026 record may reflect what Steven Grossman, president of regulatory and consulting firm HPS Group, called a “lagging indicator.” He noted that this was the case last year
“H1/2025 results are largely a reflection of ‘Phase 3 to NDA and BLA’ progress made during 2024, especially the latter half of the year,” Grossman said in a recent email interview with BioSpace . Moving forward, he predicted that the departures of leaders like Makary and Prasad will have “a small bump in the near-term” on FDA activity as previously delayed or otherwise stalled applications are expedited. Following that, he said, there will be “a larger bump in 2027 as the second half of 2026 becomes devoted to steady leadership, clearer guidance, and engaged staff.”
And the rare disease space could benefit from some of the actions taken by the Makary administration. While chronic illness is the clear priority for Health Secretary Robert F. Kennedy Jr., Makary debuted his focus on rare disease early in his tenure, teasing the plausible mechanism pathway in an April 2025 interview on The Megyn Kelly Show
The FDA under Makary issued several new policies and guidance documents related to accelerating therapies for rare disease, including the plausible mechanism pathway—intended to expedite diseases that affect an exceedingly small patient population—and Rare Disease Evidence Principles framework, also for ultrarare diseases. The devil is in the details, however, and drug developers have struggled to get a handle on how exactly they might benefit from these new pathways
Transparency overall was widely considered to be an issue under Makary and Prasad—despite the focus on “radical transparency” touted by Kennedy’s HHS
“There has been a lot of concern in the rare disease community about the patient engagement and advisory committees and the transparency,” Robyn Bent, director of Patient Focused Drug Development at the FDA, told BioSpace at BIO 2026
Some of that concern may be allayed by the recent uptick in advisory committee meetings. The FDA held one adcomm this spring for two AstraZeneca cancer drugs and another for Moderna’s mRNA-based flu vaccine, the application for which Prasad initially refused to even review. Rare disease therapies will get their turn this summer, with meetings scheduled for Capricors’ previously rejected Duchenne muscular dystrophy cardiomyopathy cell therapy and Replimune’s twice-rebuffed advanced melanoma therapy.
“We did hear that Kyle Diamantas . . . said he wanted more adcomms, and so we’re kind of wondering if this is sort of in response to that,” Capricor CEO Linda Marbán said during an interview with BioSpace last month
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While biotech—and the rare disease space—appear to be on an upswing, Suzanne Levy Friedman, a partner at law firm Honigman focused on the FDA, said she expects there will be continued “tension” at the regulator between science and politics
“There’s obviously a lot of talk about how this administration has affected the FDA, as compared to the Biden administration before it and even the first Trump administration,” Levy Friedman told BioSpace. However, she added that there is a consistent theme that sometimes gets missed
“It’s not, is this a Democratic administration or a Republican administration.” she continued. “It’s just kind of like you’ve got the people who are more focused on the science and then the people who are more focused on the politics, and somehow those things are butting heads and not always agreeing
“I think we’re going to continue to see . . . this tension between how do we protect patients and how do we at the same time foster American innovation?”
FDARegulatoryRare diseases
Heather McKenzie
