FDA Explains How Cancer Drug Developers Can Use One Trial For Both Expedited And Full Approvals – Endpoint News

The FDA’s Oncology Center of Excellence has been a bright spot within the agency in accelerating new treatments for patients. That flexibility came to full effect this morning when the FDA released new draft guidelines detailing exactly how oncology drug developers can meet both accelerated and full approval requirements with just a single randomized controlled trial.

While Congress recently passed legislation that would allow the FDA to require that confirmatory trials be recruited and passed before granting expedited approval, the agency is now making it clear that the first trial used to win the AA, if good can also serve as the trial for converting the expedited approval into a full approval.

OCE officials discussed this concept of a single study in the NEJM last October, explaining, “AA could be granted based on a planned interim analysis of the overall response rate, and traditional approval could be granted based on clinical benefit ( usually improving overall survival) at the end of the trial.”

But the design of that study must be accurate, as the FDA says in today’s draft guidance that it should be “driven for the longer-term clinical endpoint with follow-up in the same study to verify clinical benefit,” and must make sure ensure that the accelerated kink does not introduce unintentional bias.

So what are the benefits of such an approach? FDA points to “a more thorough safety assessment and earlier definitive evidence of the benefit-risk balance,” as well as reducing the risk of stopping development of the drug too early, or a drug with a limited overall response rate that could end up as an operating system improvement. In addition, the randomized trial could be conducted in patients in an earlier treatment setting, the design adds, so that the drug would reach more patients in whom efficacy could be greater.

In terms of logistics, the design notes: “The sample size of the trial should be chosen to have sufficient power to detect a clinically meaningful and statistically significant improvement in both the accelerated approval endpoints (e.g., response rate) and verification of clinical benefit (e.g., PFS or OS).”

Because the cancer treatment landscape is constantly evolving, the FDA explains that sponsors should discuss any updates with the agency, which could result in delayed expedited filings until results are available for a traditional approval. That could be a sticking point for the industry, which, if they run one trial and a confirmatory follow-up, can monetize the AA while the follow-up trial is underway.

The FDA also makes it clear, as stipulated with the passage of the omnibus late last year, that the agency “may, as appropriate, require that studies intended to verify clinical benefits be underway prior to approval, or within a certain period afterwards.” the date of approval of the product in question.”

Such confirmatory studies should be conducted with “due diligence,” the agency notes, as OCE officials previously explained in the NEJM how the median time for oncology accelerated approvals to confirm benefit or fail was longer if the confirmatory study was started after approval. The guidance also does not address expedited ways the FDA can withdraw AAs if they fail those confirmatory studies, which were also included in the omnibus.

Outside of oncology, Eisai and Biogen’s Alzheimer’s drug Leqembi (lecanemab) recently adopted this strategy, building on the results of the same study to receive accelerated approval in January, with full approval expected sometime before the July 6 PDUFA date.






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