Experimental therapies to treat rare diseases have always faced a difficult path to reach those who need them. The Food and Drug Administration says it is moving forward with new protocols to speed approvals, but criticism has grown in recent months that scientific and political pressures and staff cuts are affecting the agency’s approach to standards and regulatory requirements, which are actually hindering the delivery of these treatments to patients.
Much of the criticism has been aimed directly at FDA Commissioner Marty McCulley.
“The problem is that the secretary has replaced standards of safety and effectiveness with fear and support,” Rep. Jake Auchincloss (D-Mass.) told CNBC’s Becky Quick at the CNBC Cures Summit in New York City on Tuesday.
Mr. Auchincloss added that Mr. McCurry’s actions “undermine patient trust in the treatments brought to market, which in turn undermines innovators’ ability to bring medicines to market with confidence.”
Rick Santorum, a former Republican senator from Pennsylvania who initially supported McCulley’s appointment to the FDA, said on CNBC Cures Summit that what McCully is saying is inconsistent with what the agency is doing. He said Macallie “regulates by press release.”
“Certainly President Trump thinks things are going well, but what’s happening on the ground is not,” he said. “Government agencies are a little confused,” he added.
The Trump administration is taking a stand to fight rare diseases and discover new and innovative treatments. However, many in the rare disease community, as well as pharmaceutical companies, have been critical of the FDA’s approach, particularly regarding the flexibility of treatments for these rare diseases compared to other treatments. Many pharmaceutical executives, doctors, and patient advocates recently participated in a Senate hearing on how FDA bureaucracy is stopping innovation.
“We’re hemorrhaging the population and we’re going to see more delays as approvals catch up,” Santorum said at a CNBC Cures event, adding that this was “not what[President Donald Trump]intended.”
UniQure Inc., which is working on an experimental gene therapy for Huntington’s disease, said Monday that the FDA has asked the company to conduct another study, saying data collected in the company’s study did not provide the evidence of efficacy needed to support a marketing application.
“Although we did not reach an adjustment in the filing pathway based on the Phase I/II data, we believe the completeness and durability of the data warrant continuing a substantive dialogue about how FDA’s stated commitment to regulatory flexibility is appropriately applied in this context,” UniQure CEO Matt Kapusta said in a statement.
Approximately 41,000 people in the United States have Huntington’s disease, and more than 200,000 people are at risk for genetic Huntington’s disease, according to data from the Huntington’s Disease Society of America.
Former FDA Commissioner and Pfizer board member Dr. Scott Gottlieb said during a panel discussion at the CNBC Cures Summit that approval decisions for rare disease treatments “are dealing with incomplete data sets, small trials, (and) dealing with randomization to natural history studies rather than placebo-controlled trials.”
“In some situations, it can be difficult to see clear benefits,” he says. “It requires a lot of judgment on the part of the review staff, it requires the involvement of senior staff who have extensive experience in considering these types of clinical trial configurations, and it requires the involvement of senior staff who are willing to adjust in specific circumstances and accept some degree of uncertainty.”
Over the past two years, the FDA has experienced significant staffing reductions, with major changes felt within the Center for Drug Evaluation and Research division.
“We continue to lose the quality of human resources.”
“When you lose people who have been doing this job for many years, and you continue to lose those great people, it starts to affect review decisions,” Gottlieb said. “Part of that can be driven by the direction of some of the people who are currently leading these centers, but part of it is the loss of very senior people who in the past were intervening in some of these decisions and trying to get them across the finish line. I saw that situation occur when I was at the agency, and the people who were always engaged in that kind of involvement are now gone.”
Regarding the loss of expertise, Gottlieb said the FDA’s oncology review staff used to number about 100 people. Currently, the number of staff is less than 60. “This is a clear loss of qualified reviewers and it is clear that those who have left the oncology review staff are some of the more senior reviewers,” he said.
Gottlieb said the full response letter is likely to be affected. A complete response letter, a notice the FDA sends to drug applicants when the review cycle is complete, cannot approve a product in its current form, which outlines the changes that need to be made for approval.
In 2024, the FDA approved 20 drugs through the expedited approval process. Last year, only nine cases were approved through the same route. “That’s a pretty significant decline in just one year. In a situation like this, you can see the impact of losing experienced review staff,” Gottlieb said.
Santorum also pointed to the leadership of Vinay Prasad, the agency’s director of biologics and vaccines. Santorum said Prasad “has a long history of not supporting accelerated approvals.”
“There are department heads who have been critical of this for years, and now we’re seeing the results,” he said.
on monday, pfizer CEO Albert Bourla said at the TD Cowen Healthcare Conference that Prasad was ignoring the advice of FDA scientists.
“I don’t think the current coach is following the recommendations of his staff,” Bourla said.
Last month, the FDA’s Center for Biologics Evaluation and Research refused to review Moderna’s mRNA-based influenza vaccine, but reversed course a week later when the company amended its application. The Bureau of Statistics report said internal reviewers initially supported moving forward with the application.
When asked about the change in decisions during an appearance on CNBC in February, McCurry said that the FDA’s new approach of providing detailed explanations of why drugs were not approved “made it a little harder to find someone to hold accountable for certain products that were not approved.”
He also outlined the FDA’s proposed new system for approving customized drugs and treatments for rare diseases. In addition to creating new avenues for tailored therapies that have only been tested in small numbers of patients due to the challenges of conducting large-scale studies, this would also create a standardized process for approving experimental treatments and, importantly, offer companies the potential to commercialize them.
“This system is set up for common diseases, not rare diseases,” McCurry said.
Mr. Auchincloss argued that public debate and criticism of the FDA’s recent regulatory decisions is currently undermining the agency’s core mission of providing clear and confident approval pathways for new treatments.
“I think Mr. McCurry and Mr. Prasad need to be removed immediately, and the administration needs to bring someone to Congress with bipartisan support to start creating a seat under the FDA,” he said.
During the panel discussion, Gottlieb said he and McCulley “go back a long way” and were “very focused” on advancing treatments for rare diseases when Trump was on the committee.
“There’s a disconnect right now between what’s happening in the market, what innovators are feeling, and what I think the president’s desires are,” he said.
