Legislation would set expiration for FDA’s accelerated approvals

Regulatory NewsRegulatory News | 09 March 2022 |  By 

New legislation, introduced by a top Democrat in the House of Representatives, would codify the US Food and Drug Administration’s authority to require that drug sponsors complete postmarketing studies on drugs that receive accelerated approval.
The Accelerated Approval Integrity Act (H.R. 6963) would also set a 5-year limit for how long a drug can stay on the market without confirmation of clinical benefit or significant progress toward that goal. The bill was introduced on 07 March 2022 by Rep. Frank Pallone (D- NJ), chairman of the House Energy and Commerce Committee.
“The Accelerated Approval Program allows patients to access innovative new drugs while the manufacturer and FDA conduct additional studies to confirm the product’s clinical benefit,” Pallone said in a statement. “However, under the current system, some products have been allowed to stay on the market for far too long without clinical trials that demonstrate a real clinical benefit for patients. Patients deserve to know that the drugs they are taking are safe and effective. I’m introducing the Accelerated Approval Integrity Act to protect patients and provide FDA with the authority it needs to ensure approved drugs provide a clinical benefit. The bill would also streamline the process for taking products off the market if no clinical benefit is proven in a timely manner.”
The issue of accelerated approval was discussed by legislators during a February 2022 hearing about the reauthorization of the FDA’s user fee programs for human drugs and biosimilars, set to expire on 01 October 2022 unless Congress acts to reauthorize them. The reauthorization of the Prescription Drug User Fee Act (PDUFA VII) could serve as a vehicle of passing changes to the accelerated approval program if Pallone’s legislation does not advance as a stand-alone bill. (RELATED: User fee reauthorization process kicks off in Congress, Regulatory Focus 03 February 2022)
How the pathway works
FDA launched the accelerated approval program in 1992, offering a path to bring life-saving drugs and biologics to the market faster using surrogate endpoints that predict clinical benefit rather than waiting for more mature data on irreversible morbidity or mortality. The program is available for drugs and biologics that treat serious or life-threatening diseases or conditions.
The FDA currently requires drug sponsors to conduct post-marketing studies to confirm clinical benefit as part of the accelerated approval program and there are mechanisms to remove drugs from the market that don’t show benefit. However, in practice those tools are “cumbersome, resource-intensive, and seldom used,” Pallone said.
The accelerated approval program has been controversial, gaining praise for expediting effective treatments while also facing criticism for leaving therapies of questionable patient benefit on the market for too long. Recently, the advocacy group Friends of Cancer Research released a white paper calling for changes to the program, including better guidance on the surrogate endpoints used in accelerated approvals and requiring confirmatory trials to have enrolled a pre-determined number of patients at the time of the marketing application (RELATED: FDA’s accelerated approval program: Is change on the way? Regulatory Focus 11 October 2021).
While the agency rarely seeks the withdrawal of drugs granted accelerated approval, it recently undertook a review of “dangling” oncology accelerated approvals – indications with confirmatory trials that have not yet met postmarking requirements. After discussions with FDA, several drugmakers in late 2020 and early 2021 withdrew indications for their drugs that did not meet the primary endpoints for overall survival in confirmatory studies. FDA also convened its Oncology Drugs Advisory Committee to review six other indications for potential withdrawal. (RELATED: Industry-wide accelerated approval review yields four withdrawals, Regulatory Focus 10 March 2021; ODAC recommends pulling 2 of 6 accelerated approvals, Regulatory Focus 30 April 2021)
What’s in the bill?
If enacted, the legislation would require manufacturers to enter into an agreement with FDA on how the post-marketing studies will be conducted before the agency can grant accelerated approval, including specifics such as enrollment targets, study protocol, and a target study end date. The bill would also allow FDA to require that confirmatory studies are underway at the time of accelerated approval and require more frequent updates on the study’s progress.
The bill would also make it easier for FDA to take drugs off the market if they don’t show benefit. FDA could withdraw a drug if the sponsor fails to conduct the post-marketing study, if the sponsor fails to achieve agreed upon study targets, or if the post-marketing study fails to confirm clinical benefit. The bill also outlines an expedited procedure for withdrawal of a drug, including due notice and opportunity for a written appeal to FDA, public comment, and the potential to convene an advisory committee.
The proposed legislation also features an automatic expiration provision that would allow the accelerated approval to expire one year after the target post-market study completion date agreed upon with the FDA and no later than 5 years after the date of the drug’s accelerated approval. Drugs could stay on the market if the post-approval study confirmed the clinical benefit or if the FDA determined that sufficient progress had been made on the confirmatory trial.
Accelerated Approval Integrity Act text


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