To Stay: Two More Cancer Indications With ‘Dangling Approvals’

Approvals of two more cancer indications that had been granted accelerated approval by the US Food and Drug Administration (FDA) are going to stay in place, at least for now. This was the verdict after the second day of a historic 3-day meeting (April 27–29) and follows a similar verdict from day one.

Federal advisers so far have supported the idea of maintaining conditional approvals of some cancer indications for a number of immunotherapy checkpoint inhibitors, despite poor results in studies that were meant to confirm the benefit of these medicines for certain patients.

On the second day (April 28) of the 3-day FDA meeting, the Oncologic Drugs Advisory Committee (ODAC) supported the views of pharmaceutical companies in two more cases of what top agency staff call “dangling accelerated approvals.”

ODAC voted 10-1 in favor of maintaining the indication for atezolizumab (Tecentriq) for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial.

ODAC also voted 5-3 that day in favor of maintaining accelerated approval for pembrolizumab (Keytruda) for first-line cisplatin- and carboplatin-ineligible patients with advanced/metastatic urothelial carcinoma.

The FDA often follows the advice of its panels, but it is not bound to do so. If the FDA were to decide to strip the indications in question from these PD-1 medicines, such decisions would not remove these drugs from the market. The three drugs have already been approved for a number of other cancer indications.

Off-label prescribing is not uncommon in oncology, but a loss of an approved indication would affect reimbursement for these medicines, Scot Ebbinghaus, MD, vice president of oncology clinical research at Merck & Co (the manufacturer of pembrolizumab), told ODAC members during a discussion of the possible consequences of removing the indications in question.

“Access to those treatments may end up being substantially limited, and really the best way to ensure that there’s access is to maintain FDA approval,” Ebbinghaus said.

Another participant at the meeting asked the panel and the FDA to consider the burden on patients in paying for medicines that have not yet been proven to be beneficial.

Diana Zuckerman, PhD, of the nonprofit National Center for Health Research, noted that the ODAC panel included physicians who see cancer patients.

“You’re used to trying different types of treatments in hopes that something will work,” she said. “Shouldn’t cancer patients be eligible for free treatment in clinical trials instead of paying for treatment that isn’t proven to work?”

Rapid Development of PD-1 Drugs

Top officials at the FDA framed the challenges with accelerated approvals for immunotherapy drugs in an April 21 article in The New England Journal of Medicine. Over the course of about 6 years, the FDA approved six of these PD-1 or PD-L1 drugs for more than 75 indications in oncology, wrote Richard Pazdur, MD, and Julia A. Beaver, MD, of the FDA.

“Development of drugs in this class occurred more rapidly than that in any other therapeutic area in history,” they wrote.

In 10 cases, the required follow-up trials did not confirm the expected benefit, and yet marketing authorization for these drugs continued, leading Pazdur and Beaver to dub these “dangling” accelerated approvals. Four of these indications were voluntarily withdrawn. For the other six indications, the FDA sought feedback from ODAC during the 3-day meeting. Over the first 2 days of the meeting, ODAC recommended that three of these cancer indications remain. Three more will be considered on the last day of the meeting.

Kerry Dooley Young is a freelance journalist based in Washington, DC. She earlier covered health policy and the federal budget for Congressional Quarterly/CQ Roll Call and the pharmaceutical industry and the Food and Drug Administration for Bloomberg. Follow her on Twitter at @kdooleyyoung.

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