The FDA will reassess 6 indications for immune checkpoint inhibitors that were granted accelerated approval but failed to prove clinical benefit in confirmatory trials.
The FDA will reassess 6 indications for immune checkpoint inhibitors that were granted accelerated approval but failed to prove clinical benefit in confirmatory trials in a public meeting of the Oncologic Drugs Advisory Committee on April 27-29. The discussion will cover drugs being used to treat patients with breast, urothelial, gastric, and hepatocellular cancers.
Initiated by the FDA’s Oncology Center of Excellence, the hearings will allow external experts and patients to provide their insight on the treatments before FDA staff makes final decisions on the continued approval of the indications in question.
The indications up for discussion, which involve 3 drugs, include:
The meeting was announced after several voluntary drug indication withdrawals by pharmaceutical companies and is part of an industry-wide evaluation of accelerated approvals in oncology that saw confirmatory trials fail, according to the FDA.
In addition to the 6 aforementioned indications up for discussion, 4 others have either already been voluntarily withdrawn or are going to be voluntarily withdrawn following pharmaceutical companies’ discussions with the FDA:
These withdrawals and the impending assessments put a spotlight on the FDA’s accelerated approval program, which allows drugs to gain indications based on a surrogate end point. This facilitates quick approval and makes drugs available to patients while pharmaceutical companies conduct the required confirmatory trials to prove clinical benefit and earn regular approval for the indication.
“We are committed to ensuring the integrity of the accelerated approval program, which is designed to bring safe and effective drugs to patients with unmet medical needs as quickly as possible. The program allows the FDA to approve a drug or biologic product intended to treat a serious or life-threatening condition based on an outcome that can be measured earlier than survival that demonstrates a meaningful advantage over available therapies,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement. “However, when confirmatory trials do not confirm clinical benefit, a reevaluation must be performed to determine if the approval should be withdrawn.”
Although the accelerated approvals provide patients with potentially life-changing drugs more quickly than the traditional approval pathway, the subsequent withdrawals may create a complicated landscape for stakeholders, from payers to physicians and patients.
Joseph Alvarnas, MD, editor-in-chief of Evidence-Based Oncology™, a publication of The American Journal of Managed Care® (AJMC®), gave his take on the implications for patients and payers in a video interview with AJMC® after news of the upcoming meeting broke.
And when it comes to the current situation, Alvarnas only anticipates similar actions going forward. When you set up a system to streamline the adoption of the newest agents, it is inevitable that there will be at least some that require reevaluation.
Just 6% of the oncology indications under the accelerated approval program, including the 4 recent voluntary withdrawals, have been withdrawn, according to the FDA briefing. Alvarnas admitted that he is not surprised at the current initiative and expects more drug reassessments down the line.
He said, “One of the challenges is that as you set up a system to enhance the throughput of new agents—and I strongly favor that, because I think for patients and families who need access, getting speed to access is really important, especially in the cancer domain—the ability to dial back based upon further aggregated data is an essential function of a system which also imparts greater speed.”
FDA in brief: FDA Oncologic Drugs Advisory Committee to review status of six indications granted accelerated approval. FDA. March 11, 2021. Accessed March 12, 2021. https://www.fda.gov/news-events/fda-brief/fda-brief-fda-oncologic-drugs-advisory-committee-review-status-six-indications-granted-accelerated