DIA: Marks questions the need for new conditional approval pathway

San Diego – The US Food and Drug Administration’s (FDA) top biologics official said the proposed Promising Pathways Act would lower the bar for approving treatments for rare diseases and that the existing accelerated approval pathway suffices in bringing treatments to the market that fulfill unmet medical needs.

Speaking at the DIA 2024 Global Annual Meeting on 18 June, Peter Marks, director of the Center for Biologics Evaluation and Research (CBER), was asked to address the status of the accelerated approval pathway, as well as the changes to the program prompted by the Food and Drug Omnibus Reform Act (FDORA).

Marks, along with other experts on the panel, reiterated his support for the accelerated approval program for bringing rare disease and other treatments for unmet medical needs to market.

The accelerated approval program is available to drugs that treat serious or life-threatening conditions that fulfill unmet medical needs. It allows FDA to approve drugs based on a surrogate or intermediate endpoint until confirmatory studies are completed to show a drug’s clinical effectiveness.

The moderator of the session, Danielle Friend, senior director and US head of regulatory policy at Johnson & Johnson, cited recent research published in the Journal of the National Comprehensive Cancer Network showing that FDA’s accelerated approvals program is working in bringing life-extending treatments to patients with rare cancers.

The study found that from 2006 to 2022, accelerated approvals provided 911,000 cancer patients with an estimated 263,000 additional life years resulting from 69 different therapies and drugs with an orphan designation approved through the accelerated approval pathway provided 264,061 patients an estimated 145,413 life years gained, a 16.5 percent increase over the standard of care. The study also notes an overall increase in net life years, even when accounting for life years lost by patients with triple-negative breast cancer who took treatments granted accelerated approval that ultimately proved to be inferior to the standard of care.

When asked by Friend to address his thoughts on accelerated approvals and the FDORA reforms, Marks said that “accelerated approvals [are] an important pathway for us” to bring life-saving products to patients sooner. The program is “a little controversial, and like most pathways we have a certain amount of latitude, and when we use that latitude widely it allows us to take actions on important products to get to patients in need.”

He added that the FDORA provisions “put a little teeth in there and in that we can require that clinical trials are underway and that we help to avoid what happened in the past [with] dangling approvals.”

FDORA, which was enacted on 29 December 2022 as part of the Consolidated Appropriations Act, prompted several reforms to the accelerated approval process, including requiring a postapproval study be underway prior to granting accelerated approvals and the expansion of expedited withdrawal procedures if a sponsor fails to conduct a postapproval study. Sponsors are also required to submit periodic progress reports regarding the progress of the postapproval studies every 180 days.

Edward Neilan, chief medical and scientific officer for the National Organization for Rare Disorders (NORD), said that accelerated approval is “extremely important for rare diseases and is very well suited to the rare disease space.”

Alexis Miller, the acting lead of global regulatory policy for Merck, said that accelerated approvals is only available for serious diseases, so it only affects a narrow subset of the population. She noted that the pathway “is great for meeting unmet need. It is also a great driver of innovation.”

Marks was asked to address proposed legislation that would create another accelerated approval pathway for rare diseases under the Promising Pathway Act, which has been introduced in both chambers of Congress.

Under the PPA, FDA would establish a rolling, real-time, priority review pathway that would allow for provisional approval of drugs intended to treat, prevent, or diagnose serious or life-threatening diseases or conditions. Drugs would not need to show definitive proof of efficacy upon provisional approval. Such approvals would run from two to eight years. The bill was most recently introduced on 8 June 2023 by Sens. Mike Braun (R-IN) and Kirsten Gillibrand (D-NY) and introduced in the House on 7 July 2023 by Rep. Mike Gallagher (R-WI).

Marks said he does not see the need for the pathway that would be created by the legislation. “With accelerated approval we already have a tremendous amount of leeway,” he said.

He questioned whether there is a need to “go another step lower.” He also questioned the value proposition on whether payers would pay for provisionally approved products. Marks added that in the product development “ecosystem” there may be a perception that provisionally approved products are not as good as products approved through the accelerated approval pathway.

Neilan said that NORD has similar concerns with the legislation and worries that payers may not cover provisionally approved drugs.

Marks also sought to dispel the misconception that a drug is a failure if it fails confirmatory trials. Instead, there can be many reasons a product fails these trials that may not necessarily relate to the product itself. Such failures, for example, can include the lack of necessary data to support the drug’s efficacy in confirmatory trials.

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DIA: Marks questions the need for new conditional approval pathway

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