The sudden departure of Vinay Prasad, M.D., from the FDA this week again threw the cell and gene therapy field into uncertainty. But this time, the unknown is hitting the industry in a different way from when Prasad was tapped to lead the Center for Biologics Evaluation and Research (CBER) less than three months ago.
When Prasad assumed the CBER director role, overseeing cell and gene therapies and other blood products in May, people were worried that he would suffocate the industry with a remarkably tight regulatory hand, given his objections to several past FDA decisions.
But now, Prasad’s sudden exit suggests that his replacement is “likely to fall further along the ‘right to try’ arm of the MAHA-RFK policy side,” Leerink Partners analyst Mani Foroohar, M.D., said in an interview with Fierce Pharma.
President Donald Trump signed the Right to Try Law during his first term in 2018. It was designed to let people who are terminally ill with no commercial treatment options gain access to drugs that are not approved by the FDA. Besides the namesake law, the term “right to try” can also be used more loosely to describe efforts that aim to shift the gatekeeping power from the FDA to patients more broadly, including during the drug approval process.
An 'anti-Trump' FDA official
Prasad represents the very opposite of “right to try.” As Allysia Finley wrote in a conservative Wall Street Journal opinion piece shortly before his exit, Prasad is a “top FDA appointee who doesn’t think patients can be trusted to make their own healthcare decisions.”
Rather than lowering the regulatory bar, Prasad has argued for more scrutiny from the FDA and less reliance on surrogate endpoints in drug approval decisions.
In his pre-FDA life, Prasad, a practicing hematologist-oncologist, worked as a professor in the epidemiology and biostatistics department at the University of California, San Francisco. As a biostatistician, numbers and statistical analysis play a key role in his scientific focus, Foroohar noted.
Before taking the CBER job, Prasad had been openly critical of the FDA’s accelerated approvals, including that of Sarepta Therapeutics’ Duchenne muscular dystrophy gene therapy Elevidys, which survived two placebo-controlled trials, missing statistical significance on their primary endpoints to receive its FDA approvals. He had also taken a hard line against the adoption of a deep tumor response called minimal residual disease negativity as a potential accelerated approval endpoint for multiple myeloma drugs. Instead, he insisted on these drugs showing a benefit on the more stringent overall survival marker, which may take years and almost impractically large clinical trials.
Despite Prasad’s vocal dissent over some of the FDA’s previous decisions, Foroohar said he grew more comfortable with Prasad’s approach after spending more time observing Prasad the regulator, versus Prasad the YouTuber.
“His approach to cell and gene therapy for inherited illnesses has been fairly straightforward and transparent, and I found relatively little to quibble with in terms of statistical rationale and scientific reason in that space,” Foroohar said.
But Prasad’s philosophy of higher regulatory standards apparently infuriated conservatives.
In a July 20 post on social media, Laura Loomer, a right-wing activist who reportedly has access to President Donald Trump, called out the Prasad-led CBER’s recent complete response letters to Ultragenyx’s Sanfilippo syndrome type A gene therapy and Capricor Therapeutics’ Duchenne cell therapy, labeling them as “arbitrary delays” that were “not based on science, but on his own left-wing agenda.”
“Prasad’s regulatory philosophy is fundamentally anti-Trump,” Loomer continued.
“He criticized Trump’s Right-To-Try policies, calling the President ‘incorrect’ and blaming pharmaceutical companies, not the FDA, for delays in drug access,” she wrote.
One final push
But it’s likely Sarepta’s Elevidys that ultimately toppled Prasad.
The FDA and Sarepta were engaged in a regulatory tug of war over whether Elevidys should remain on the market after several deaths related to acute liver failure raised safety concerns over the gene therapy.
The agency initially forced Sarepta to halt shipments to all Duchenne patients and was reportedly eyeing additional study requirements before it would back the treatment again. But the agency made a U-turn on Monday, recommending that Sarepta resume giving Elevidys to Duchenne patients who can walk. Yet the agency didn’t address the deaths that it had originally cited in its request for the pause.
Grievances over the FDA’s suspension reached Sen. Ron Johnson, R-Wis., who drafted the Right to Try law. Johnson raised the concern with the White House on Monday morning, Politico reports, and the FDA’s reversal came Monday afternoon, with a line that said, “The patient community is an important voice, and the FDA will continue to listen to and respond to thoughts from the community impacted by DMD.” News of Prasad’s exit came out Tuesday evening.
To Foroohar, the backtracking and its close proximity to Prasad’s departure suggest that a more patient advocacy-centric approach based on the “right to try” rationale is gaining influence over the FDA. That led the Leerink analyst to predict that Prasad’s successor will likely be someone who sides closer with the “right to try” camp on the regulatory spectrum.
FDA Commissioner Marty Makary, M.D., on Wednesday named newly appointed Center for Drug Evaluation and Research head George Tidmarsh, M.D., Ph.D., as acting director of CBER, and Scott Steele, Ph.D., and Brittany Goldberg, M.D., as deputy directors of CBER.
The Trump administration is considering splitting up CBER into two departments, with one focused on vaccines and the other on therapeutics like cell and gene therapies, Politico reports, citing three people familiar with the discussions.
The rise of 'right to try'
Prasad’s ouster—and potential replacement with a “right to try” supporter—is “probably an incremental positive, at least on sentiment and optionality for genetic medicine companies for rare disease,” Foroohar said.
However, allowing “right to try” to take over the FDA may have negative effects over “the longest of long term,” the analyst said, conceding that his opinion would be different if he had a child with a rare disease.
With a low regulatory bar, Foroohar argued that some drugs will reach the market with “meaningfully less stringent data standards, and you’re going to have surprises.”
The industry already has an example of what those surprises might look like.
The three acute liver failure deaths linked to Elevidys and an experimental Sarepta gene therapy all happened in non-ambulatory patients with muscular dystrophy. The FDA had originally granted Elevidys a very narrow conditional nod in 4- and 5-year-olds, but the agency significantly expanded the drug’s label last year to cover almost all patients, in another controversial decision that critics said was not backed by data. At that time, concerns had already surfaced around the drug’s profile in non-ambulatory patients, in whom the drug has shown limited data and is only authorized under the accelerated approval pathway.
“I worry about the safety of those boys,” Aravindhan Veerapandiyan, M.D., a pediatric neurologist at Arkansas Children’s Hospital, told Stat at the time.
A very aggressive right-to-try approach may lead to more such cases, which can be harmful to everybody, Foroohar argued.
“It is not good for the sector. It’s not good for the patients. It undermines the mission of the agency,” he said. “The longer term, it undermines the value of these therapies and the trust that patients, families, payers, the government [and] society as a whole can give these therapies.”
“So, when it comes to regulatory barriers, as much as industry might want them to be permissive, this is an area where you want the regulatory barriers to be adequately high,” he added.
Cell and gene therapy, now in its fourth year of a bear market, has been one of the worst-performing fields in biotech, the Leerink analyst noted.
No matter which side of the regulatory spectrum the new CBER director may fall—from highly stringent to closer to right to try—a candidate with extensive academic credentials, clinical or drug development experience and preferably prior regulatory experience would be reassuring to the industry, Foroohar said.
Consistency also matters. Even if the new CBER director hints at a more permissive approach, the agency needs to maintain that “in a consistent manner for a reasonable period of time so investors are comfortable projecting forward,” Foroohar suggested.
Sustained regulatory flexibility will make it easier for drugmakers to model clinical trials and time to accelerated approvals, as well as raising the right money and hiring the right size of teams, he said, noting, “Changing the regulatory scheme every few months is probably the most destructive approach.”