The cell and gene therapy sector faces significant uncertainty following the resignation of Peter Marks, who stepped down as head of the FDA's Center for Biologics Evaluation and Research (CBER) on Friday, citing differences with Health and Human Services Secretary Robert F. Kennedy Jr.
Marks, who led CBER since 2016, was widely regarded as the industry's most influential champion within the regulatory agency, overseeing approvals for dozens of groundbreaking therapies including the first gene therapy, first cellular treatment for cancer, and first CRISPR gene editing medicine.
"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," said Stephan Grupp, head of Children's Hospital of Philadelphia's cell therapy and transplant section, who helped develop the first CAR-T therapy for cancer. "This is a huge loss to the field and to the FDA."
A Legacy of Innovation and Flexibility
During his tenure, Marks championed flexible regulatory approaches that accelerated development pathways for novel therapies, particularly for rare diseases. He pushed the agency to develop specialized expertise and expand staffing to handle the growing pipeline of complex cell and gene therapy applications.
Katherine High, a prominent gene therapy researcher, credited Marks with establishing the regulatory infrastructure that enabled these therapies to advance: "Peter Marks' vision, scientific rigor, and outstanding clinical judgment have been key reasons that cell and gene therapies have progressed as they have."
Since 2017, the FDA has approved 43 cell or gene therapies under Marks' leadership, according to the Alliance for Regenerative Medicine. Many of these approvals came through accelerated pathways that Marks advocated for, believing such flexibility was essential to encourage investment in treatments for rare diseases.
"Although we're a regulatory agency," Marks said at a patient advocacy meeting 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."
Controversial Decisions and Industry Impact
Marks' willingness to approve therapies based on limited evidence sometimes generated controversy. Perhaps the most notable example was his decision regarding Sarepta Therapeutics' Elevidys, the first gene therapy for Duchenne muscular dystrophy. Despite mixed clinical results and opposition from other FDA officials, Marks twice overruled fellow staffers to approve the therapy and later expand its clearance.
Pat Furlong, head of advocacy group Parent Project Muscular Dystrophy, described Marks as a "pivotal figure" in advancing gene therapies for Duchenne, "working tirelessly to ensure the voices of patients and their families" informed regulatory decisions.
His departure comes at a particularly challenging time for the cell and gene therapy sector, which has already experienced a significant pullback in funding. According to data published in Nature Biotechnology, CGT companies raised just $500 million across 16 venture rounds by August 2023, compared to $8.2 billion from 121 deals in 2021.
Market Reaction and Future Outlook
The news of Marks' exit sent ripples through the industry, with several gene therapy companies seeing their stock prices fall on Monday. Analysts expressed concern about potential regulatory shifts that could affect development timelines and approval standards.
"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.
RBC Capital Markets' analyst Brian Abrahams suggested companies developing new Duchenne therapies could face a "stricter path to market" if incoming leadership changes direction, while treatments for autoimmune diseases might receive "less leniency."
However, some industry observers remain cautiously optimistic. New FDA Commissioner Marty Makary has signaled support for flexible approaches to rare disease treatments in his first media interview.
"When you talk about a genetic issue that affects 52 kids in the world... or 15 kids... you can't expect the companies to do a randomized, controlled trial; you'll kill innovation. You'll kill investment in those innovative ideas," Makary told former Fox News journalist Megyn Kelly.
Makary indicated the FDA would implement a conditional approval pathway based on "plausible scientific mechanism" for incurable diseases affecting small populations—potentially good news for rare disease-focused cell and gene therapy developers.
Industry Challenges Beyond Regulation
Beyond regulatory uncertainty, the cell and gene therapy sector faces additional headwinds, including potential tariffs that could disrupt global supply chains critical to manufacturing these complex therapies.
"One of the major issues is that the industry operates from a global supply chain, relying heavily on imported materials," explained Jonathan Wofford, chief commercial officer at CGT software company Title21 Health Solutions.
Audrey Greenberg, founder of the Center for Breakthrough Medicines, a CGT-focused CDMO, noted that key components for cell and gene therapy manufacturing—including viral vectors, plasmids, and critical reagents—often come from overseas. "If tariffs hit these key components from China or the EU, we're going to see increased cost of goods, tighter margins, more volatility and production timelines. And that's bad news for patients and companies."
Cell and gene therapies already rank among the most expensive treatments available, with prices ranging from $3-4 million for one-time treatments, making coverage and revenue challenges significant.
The Path Forward
Despite these challenges, many industry leaders believe the foundation Marks established will endure. Stifel analyst Paul Matteis noted, "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."
Nicole Verdun, director of the Office of Therapeutic Products that reviews gene therapies, has also been an "outspoken advocate" for accelerated approvals, according to analysts at William Blair.
In his resignation letter, Marks emphasized the importance of continuing to expedite treatment development for genetic diseases: "If thoughtfully approached and further developed and refined, these treatments have the potential to transform human health over the coming years."
For a field that has already transformed treatment paradigms for numerous previously untreatable conditions, maintaining regulatory momentum will be crucial. As Ignacio Núñez, chief operations officer at CDMO CellReady, observed: "The key is who the new leader will be and how fast he is able to articulate a cohesive direction for the field... It doesn't need to be negative. It could also be positive."
The next few months will be critical in determining whether the regulatory framework Marks championed will continue to support innovation in this transformative but still-evolving therapeutic space.
