Cell, gene therapy makers lose a champion at FDA with exit of Peter Marks

Over the past decade, several dozen cell and gene therapies have reached market in the U.S., bringing with them the promise of long-lasting benefits for serious diseases. 

Peter Marks’ fingerprints are all over those approvals. As head of the Food and Drug Administration’s Center for Biologics Evaluation and Research since 2016, Marks oversaw the clearances of the first gene therapy, the first cellular treatment for cancer and the first CRISPR gene editing medicine, among others. He pushed the agency to be more flexible in reviewing those drugs, endorsing speedy development pathways that drew both praise and criticism. 

Marks, who as CBER head also leads the agency’s vaccine work, resigned Friday, citing differences with Health and Human Services Secretary Robert F. Kennedy Jr. His exit leaves cell and gene therapy developers without their biggest proponent at the FDA. And it also adds another dose of uncertainty to what’s already a challenging time for the makers of these medicines, many of which are struggling to attract investment. 

Stephan Grupp,  head of Children’s Hospital of Philadelphia’s cell therapy and transplant section, called Marks “an absolute scientific and regulatory giant at the agency.”  

“He was integral to so much of the recent progress in cell and gene therapy. He kept things safe and he kept things moving. He really got it,” added Grupp, who helped develop the first CAR-T therapy for cancer. “This is a huge loss to the field and to the FDA.”

“Peter Marks’ vision, scientific rigor, and outstanding clinical judgment have been key reasons that cell and gene therapies have progressed as they have,” said Katherine High, a prominent gene therapy researcher. “His tireless commitment to building and disseminating a rigorous regulatory infrastructure for these novel therapeutics has led to a gradual but definite increase in the pace of approvals, which have now extended to gene editing as well.”

Cell and gene therapy developers have more hurdles to overcome than companies specializing in more traditional drugmaking methods like small molecules or biologics. Their products are especially complex, involving the manipulation of cells or genetic material as well as the use of specialized tools like engineered viruses to deliver them into patients. Understanding how these components work in the body and ensuring they’re safe and effective has required the creation of new regulatory frameworks as well as manufacturing processes. 

Because of their complexity, safety risks and high production costs, these therapies are often developed for rare or life-threatening diseases. The first gene therapy in the U.S. was approved in 2017 to treat an uncommon and inherited form of vision loss. That same year also saw the arrival of the first cell therapy as a last-ditch treatment for people with a stubborn blood cancer. There have been another 42 cell or gene therapy approvals since then, according to the industry lobbying group the Alliance for Regenerative Medicine.  

While running CBER, Marks pushed the agency to develop the kind of expertise and larger staff required to review these therapies, applications for which are expected to increase in the years to come. In the last 18 months alone, he and other senior leaders hired “critical scientific personnel and dramatically moderniz[ed] the regulatory framework” for the “ever-expanding” pipeline of therapies, the Alliance for Regenerative Medicine said in a statement. 

Marks advocated for using unorthodox approval pathways to accelerate development of these treatments for rare diseases, believing that doing so was the best way to entice drugmakers to invest. 

“Although we’re a regulatory agency,” Marks said at a meeting hosted by a patient advocacy group last year, regulations “have to ultimately serve getting products to patients. So we’re trying to focus on the patient, and use that to negotiate the regulations to get there as rapidly as possible.” 

Those negotiations involved regular communications with patient advocacy groups and drugmakers to develop approval paths — as well as an openness to clearing therapies based on thinner evidence of benefit. Marks was willing to do so despite the risk of approving a therapy later found to be unsafe or ineffective.

“He was our field’s biggest champion and moved mountains to improve regulatory paths to speed up treatments for children in particular with rare diseases,” said Nicole Paulk, a former UCSF researcher and the CEO of gene therapy startup Siren Biotechnology. 

Perhaps the most prominent example is in Duchenne muscular dystrophy, a progressive and deadly neuromuscular condition. Pat Furlong, the head of advocacy group Parent Project Muscular Dystrophy, said in an email that Marks has been a “pivotal figure” in advancing gene therapies for Duchenne, “working tirelessly to ensure the voices of patients and their families” informed drug research, development and regulatory decisions. That culminated in the 2024 approval of Sarepta Therapeutics’ Elevidys, the first gene therapy for Duchenne. 

Elevidys was a controversial case, however. It produced mixed results in clinical testing and missed its main goal in two placebo-controlled trials. Twice, Marks overruled fellow staffers and even other FDA leaders to approve the therapy and then expand its clearance. He argued Sarepta’s other study findings were compelling and made the case that even a small benefit in Duchenne is clinically meaningful. 

His decision was lauded by patient organizations, but rebuked by critics who thought he had improperly lowered approval standards. 

The mindset Marks instilled at the FDA may last beyond his tenure. In Duchenne, companies like Regenxbio and Solid Biosciences are following Sarepta’s lead and aiming for accelerated approvals. Similar discussions have put a first-of-its-kind Huntington’s disease gene therapy from UniQure on the path to approval, and helped advance heart treatments from Rocket Pharmaceuticals and Lexeo Therapeutics.

In his resignation letter, Marks said the agency “must do better to expedite the development of treatments” for people suffering from genetic diseases and called on the FDA to keep moving quickly. 

“If thoughtfully approached and further developed and refined, these treatments have the potential to transform human health over the coming years,” Marks wrote. 

Companies and their investors are counting on it. Murky commercial prospects have led to a pullback in funding for private as well as publicly traded cell and gene therapy developers. Marks’ departure adds regulatory upheaval to the mix, further depressing the stock prices of several gene therapy firms on Monday.

Cell and gene therapy companies “are particularly exposed to FDA disruption risks, given the need for support of science-based novel product development,” wrote Leerink Partners analyst David Risinger. 

Companies developing new Duchene therapies could see a “stricter path to market” if incoming leadership changes direction, wrote RBC Capital Markets’ analyst Brian Abrahams, in a Monday investor note. He added that there might be “less leniency” towards cell therapies for autoimmune disease, which could impact more than a dozen companies, including Kyverna Therapeutics and Cabaletta Bio. 

More broadly, the unknowns regarding Marks’ successor and whether other rank-and-file employees might also leave the agency creates more risk, wrote Mani Foroohar, another Leerink analyst. 

Some industry watchers remain optimistic, however. Baird analyst Jack Allen noted how Marks’ dispute with Kennedy appeared to center on vaccines, not novel treatments like gene therapies. The team of analysts at William Blair added that Nicole Verdun, director of the Office of Therapeutic Products that reviews gene therapies, has also been an “outspoken advocate” for accelerated approvals. Incoming commissioner Marty Makary has signaled a willingness to be flexible in the case of “ultra-rare, life-threatening diseases,” too, they added. 

“We have anecdotally heard from companies we cover that their experience has been that it’s not just Dr. Marks who believes in accelerated/flexible paths — many other leaders and reviewers at FDA are seemingly on board with his approach,” wrote Stifel’s Paul Matteis, in a separate note. 

Yet experts in the field remain worried. Grupp noted how major academic centers working on cell therapy are  “dependent on a functional FDA” and pointed to the agency’s existing staffing deficits even before the Trump administration ordered mass job cuts last week.

“This is a moment of great uncertainty across the biomedical field,” he said.

Against that backdrop, Marks could be tough to replace. Paulk called on the industry’s leaders and investors to head to Washington D.C., and “let it be known that they need to reinstate Dr. Marks at once.” Furlong, of PPMD, said that “strong, experienced leadership” is going to be critical for progress to continue. 

“It would be difficult to imagine a successor who could fill his shoes,” added High. “His departure under the current circumstances is most unsettling.” 

Ned Pagliarulo contributed reporting.

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