CDER director on accelerated approval reforms and a court decision that will 'send a chill' across rare disease drug development
At the second of two hearings before the Senate Health, Education, Labor & Pensions Committee on the must-pass legislation (by the end of September) regarding the funds from biopharma industry applications that will keep the FDA afloat over the next five years, CDER director Patrizia Cavazzoni raised particular concerns about a recent court decision while laying out several requests for congressional accelerated approval reforms.
Responding to a question from Sen. Tammy Baldwin (D-WI), Cavazzoni said she wants to work with Congress to find a solution after a recent court decision against the FDA “will send a chill into the development of rare diseases and it will disproportionately affect children with rare diseases. It’s essential to continue to generate the study of drugs in children, so this decision will really go counter to that.”
The case in question from last October saw a US appeals court overturn a prior FDA court win, saying that the agency never should’ve approved a rare disease drug because a previously approved but more expensive drug with the same active ingredient has orphan drug exclusivity barring such an approval.
The situation right now, Cavazzoni said, following the court’s decision “is a sponsor could study a disease in a very narrow segment of the population and then be able to block further approvals throughout the entire condition that that drug could address.”
Sen. Susan Collins (R-ME) also raised questions with Cavazzoni regarding CMS’ recent decision to not cover Biogen’s controversial Alzheimer’s drug, and its discussion of the safety of the drug.
Cavazzoni defended the approval, saying the data “are solid and the drug is appropriately made available to patients based on FDA’s decision. It’s important to distinguish FDA and CMS’ roles,” she said, adding that FDA is solely responsible for determining safety and effectiveness, and CMS has a different standard, reasonable and necessary, which translate into the setting in how the drug is covered.
“There are some areas when it comes to accelerated approval where we could use some help from Congress,” Cavazzoni said, noting that FDA doesn’t have the authority to require that confirmatory trials are started or be underway by the time the drug is approved, or at least have a detailed plan to conduct those trials.
“Another area we can use some help is in expediting the withdrawal of drugs when the confirmatory trials do not confirm the drug is associated with clinical benefit,” Cavazzoni said. “Right now the expedited withdrawal path is anything but expedited. It can take up to 2 years and require lots of resources and lots of administrative burden.”
Committee Chair Sen. Patty Murray of Washington acknowledged that the user fee programs in general have an important role, and they ensure that more drugs and devices cross the finish line and that the FDA gets the appropriate resources.
“It should be unthinkable that after 2 years, when FDA’s work has been more important than ever, that we would fail to get this done or force the agency to send pink slips,” Murray said, while saying that they should look back at this pandemic — from FDA’s work to review and approve vaccines quickly to other issues like testing struggles and the hydroxychloroquine debacle.
The top Republican member of the committee, Richard Burr of North Carolina, raised concerns about the current lack of funds flowing into biotech in general, and said today’s hearing was about accountability, while mentioning the need for FDA “to speed not only the review of products but their development as well.”
He also raised several concerns, highlighting several benchmarks the agency failed to meet in the last user fee agreement.
“Now FDA wants double the money for mediocre performance improvements,” Burr said. “The more you use the user fee process to bully dollars out of industry, holding them hostage, the less accountable the FDA is.”
CBER director Peter Marks also explained the current situation of Covid-19 vaccines for the youngest group of children (under 5), saying that as soon as the FDA receives an application, “we’ll move quickly. It’s one of our highest priorities.”
Again he said that an adcomm of outside experts will meet and review the data on the vaccines too, and in the next week, Marks said, the FDA will release a tentative timeline for those meeting(s) as the agency reviews these 2 applications from Pfizer and Moderna. He also stressed that the FDA can’t start or finish its reviews until the complete applications are submitted.
Companies often release statements ahead of the FDA on when such applications are fully submitted, he noted.
On the topic of vacancies, which is always a tenuous topic at the FDA as several senior vaccine and other leaders moved on recently, Cavazzoni said CDER is looking to fill roles for about 7-8% of its staff, which “isn’t a high rate for a large organization,” she said.
In response to questions over the recently unveiled McKinsey conflicts of interest with FDA regarding their opioid work, Cavazzoni stressed that CDER doesn’t have any contracts with McKinsey, and while McKinsey had worked with FDA, its work with FDA did not entail specific scientific reviews of products or processes.