Significant leadership instability at the FDA—compounded by continued workforce attrition—led to a slight slowdown in overall regulatory productivity in the first half of this year, but the agency has been catching up of late.
The FDA issued some 79 verdicts in the first half of 2026, a slight dip from 85 during the same period last year, according to BioSpace tallies. But novel approvals ticked up, from 19 in H1 2025 to 26 so far this year.
FDA approvals, and decisions more broadly, represent what Steven Grossman calls “lagging indicators.” That is, they are affected and determined by the agency’s recent performance, explained Grossman, president of policy and regulatory consulting firm HPS Group. Harmonious and efficient operations at the regulator today will manifest as high regulatory productivity months down the line.
“H1/2026 heavily reflects the chaos of the first and second half of last year,” Grossman told BioSpace in an email. He pointed in particular to “hostile management” by former Center for Biologics Evaluation and Research director Vinay Prasad, whom he said “was not interested in the smooth or fair management of CBER.”
At the same time, Grossman continued, “Lay-offs, premature retirements, and widespread uncertainty in the first half of 2025 may also have contributed to the higher numbers during that period—as dedicated FDA staff tried to move items on their desks to completion as soon as they could.”
There are signs that the agency is beginning to turn around. The FDA is looking to hire some 2,200 staffers—600 of whom have already been secured, Lowell Zeta, the agency’s acting chief of staff and deputy commissioner, said last month at BIO’s international convention.
And the regulatory doors appear to be cracking open for rare disease companies that saw more stringent action under Prasad and former FDA Commissioner Marty Makary.
As biopharma launches into the second half of 2026, BioSpace examines some of the key takeaways from the first six months—and indicators of where the FDA is headed.
FDA upheaval cramped productivity in H1 2026
The past 18 months have been marked by chaos at both of FDA’s key review divisions, CBER and the Center for Drug Evaluation and Research (CDER), both of which are currently headed by acting directors who are the sixth person to fill the role since Donald Trump took office in January 2025.
Grossman faulted the “repeated management changes” at CDER for the FDA’s slightly reduced action in the first half of 2026, while CBER decision-making became unreliable under the leadership of Prasad, who oversaw some of the FDA’s most contentious recent decisions.
In February, for instance, the former biologics chief penned a refusal-to-file letter for Moderna’s mRNA flu vaccine—a move that was widely criticized and quickly reversed. And both Prasad and Makary also spoke out publicly against uniQure’s gene therapy for Huntington’s disease. Last week, news broke that CBER is losing yet another leader, as Vijay Kumar, the FDA’s acting director in charge of cell and gene therapy, is stepping down after a year in the position.
Given the high-level instability at the agency, it’s “no great surprise that fewer products moved through the pipeline to approval-ready NDA’s and BLA’s during the first half of this year,” Grossman said.
Jefferies analyst Andrew Tsai agreed. The downturn, he told BioSpace in an email, is likely at least partly a result of the “significant turnover” of FDA leadership across both key review divisions. Further, this top-level instability “inevitably leads to a loss of decisional consistency,” Tsai said, which in turn generates “a slight sense of unpredictability.”
The appointment of acting officers while the government looks to permanently fill the positions is another challenge to productivity, according to Tsai. “Acting directors may be spending a large share of their time getting up to speed/managing internal reorganization, which leaves less time for actually running review cycles leading to delays,” he said.
But Grossman predicted that the departures of leaders like Makary and Prasad, among many others, will have two effects on the FDA’s productivity. One will be “a small bump in the near-term” as previously delayed or otherwise stalled applications are expedited. The second, he said, will be “a larger bump in 2027 as the second half of 2026 becomes devoted to steady leadership, clearer guidance, and engaged staff.”
Novel approvals, rejections rise in H1 2026
Even amid the leadership instability, the FDA issued more approvals for novel therapies in the first half of 2026—and more rejections. In addition to the uptick in approvals, the first half of this year saw eight novel drug applications rejected, compared with six in the same period last year.
One particular denial stands out for Tsai: Disc Medicine’s bitopertin, which the Massachusetts-based biotech was proposing to treat a rare blood disorder. Bitopertin was the first drug granted a Commissioner’s National Priority Voucher (CNPV) to be rejected, “somewhat discrediting the program,” Tsai said. The CNPV scheme was unveiled in June 2025 to shorten review times from 10–12 months to 1–2 months for products that align with certain federal priorities, such as addressing key medical needs and lowering drug prices.
Bitopertin was among the first batch of drugs awarded a CNPV, in October 2025. When the drug was rejected in February—because of issues with Disc’s use of a surrogate endpoint, according to the complete response letter—observers raised the possibility of unilateral decision-making within the FDA and politicization of the program, especially given reports that Prasad had been skeptical of bitopertin.
Another notable first-half rejection was for REGENXBIO’s Hunter syndrome gene therapy. RGX-121 was rebuffed in February, with the FDA citing “uncertainty” in the study’s enrollment criteria, its use of external controls and the validity of a surrogate endpoint. This, despite the biotech’s assertion that the FDA had previously signed off on the trial protocol.
The FDA under acting commissioner Kyle Diamantas appears to have changed course, telling REGENXBIO last month that existing clinical data for the gene therapy were sufficient for an accelerated approval application.
RGX-121 is one example of a product that is benefitting from the short-term bump Grossman predicted under the FDA’s current caretaker leadership. Other beneficiaries of the FDA’s seemingly more open stance on rare disease therapies include Replimune’s advanced melanoma drug and uniQure’s gene therapy for Huntington’s disease.
Cancer approvals slide as Replimune controversy rocks regulator
In line with the overall dip in the FDA’s productivity, cancer drug approvals were down slightly in the first half of 2026. The agency greenlit 23 oncology applications in H1, versus 26 during the same period last year. Only three are for novel drugs, however, while the rest are for label expansions.
The first novel oncology approval of the year was granted in March to Corcept Therapeutics’ Lifyorli, a glucocorticoid receptor blocker used with nab-paclitaxel for platinum-resistant ovarian, fallopian tube or primary peritoneal cancer. Pfizer and Arvinas notched the year’s second novel cancer approval in May when the FDA cleared their protein degrader Veppanu for certain types of advanced or metastatic breast cancer. Days later, BeOne scored an accelerated approval for its BCL-2 blocker Beqalzi for mantle cell lymphoma.
All the while, the FDA was getting pummeled by criticism over its second rejection of Replimune’s RP1 for advanced melanoma. The FDA in April declined for a second time to approve the drug, saying in its CRL that the data package was “insufficient to conclude substantial evidence of effectiveness.”
This verdict set off a storm of controversy for the agency—so much so that Makary went on CNBC to publicly defend the FDA’s decision-making process. The blowback became so severe that even Health Secretary Robert F. Kennedy, Jr. felt behooved to comment on it.
Like Disc and REGENXBIO, Replimune is now gearing up for another application for RP1. The biotech announced in May that it would refile the application following a “constructive dialogue” with the FDA, which the agency indicated it would treat as an “urgent matter upon receipt,” according to Replimune. Sure enough, the FDA accepted the resubmission on June 26, assigning a target action date of Aug. 2.
Elsewhere, the FDA approved 11 applications for immunological and inflammatory disease and three for CNS indications.
Uptick in rare disease activity includes many firsts
Amid the upheavals at the FDA, the first half of 2026 saw a greater number of rare disease decisions than in H1 2025—19 vs. 10, respectively. Of the total rare disease verdicts in H1, three were negative. Meanwhile, the first six months of 2025 saw two rejections in this space.
Two of this year’s rare disease decisions, the rebuffs of Disc’s bitopertin and REGENXBIO’s RGX-121, were among the agency’s most contentious. On the flip side, the FDA gave out a handful of game-changing approvals.
In March, Denali Therapeutics won the agency’s go-ahead for Avlayah, an enzyme replacement therapy for Hunter syndrome. Avlayah is the first new medicine for Hunter syndrome in almost two decades, according to the biotech, and the first to address the disease’s neurological complications.
That same month, the FDA cleared the first weekly therapy for achondroplasia in Ascendis Pharma’s Yuviwel. Achondroplasia, a genetic disease that impairs bone development in children, is the most common cause of dwarfism. Yuviwel will compete on the market with BioMarin’s Voxzogo, a daily injection.
In April, Regeneron’s gene therapy Otarmeni notched several firsts. The product became the first treatment of congenital hearing loss and the first therapy to target an underlying cause of deafness. It is also Regeneron’s inaugural gene therapy on the market.
By greenlighting Otarmeni, the FDA sets the stage for other gene therapies delivered directly to their target organs—with hearing loss a perfect test case. Otarmeni’s success, Mizuho analyst Graig Suvannavejh told BioSpace in March, “will likely only stimulate more interest by both industry and the investment community in gene therapies for hearing loss, as well as in the gene therapy space overall.”
