Tag Archives: FDA approval

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

Kerry Dooley Young, Medscape News: April 29, 2021


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.

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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?”

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To read the entire article, see https://www.medscape.com/viewarticle/950165

Conflicts Galore: Upcoming Accelerated Approval Cancer Panel May Be Tainted By Industry Relationships

Sarah Karlin-Smith, Pink Sheet: April 21, 2021


Six members of the FDA Oncologic Drugs Advisory Committee received conflict of interest waivers to participate in the agency’s upcoming three-day meeting to review the accelerated approval of six checkpoint inhibitor indications after the three cancer immunotherapies at issue failed to confirm clinical benefit in post-market trials raising questions about whether industry influence may heavily factor in the committee’s decision making.

The high number of waivers could mean that a majority or close to a majority of the panelists will have conflicts based on the typical number of advisors on FDA panels. The agency used to be subject to waiver limits but the 2012 FDA Safety and Innovation Act removed these restrictions.

ODAC’s 27-29 April meeting, part of the agency’s broader industry-wide effort to evaluate accelerated approvals for oncology drugs, is unprecedented in the number of drugs and indications up for accelerated approval withdrawal. The committee will discuss two indications for Tecentriq (atezolizumab); three for Keytruda (pembrolizumab); and one for Opdivo (nivolumab).

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Vinay Prasad, a hematologist-oncologist at the University of California San Francisco acknowledged that it may not always be easy to find unconflicted experts but, he said they do exist. He also argued that in this case you might be able to look at other professionals like internists who study research methods and FDA approvals, for example for panel members.

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Diana Zuckerman, president of the National Center for Health Research said that while FDA needs some people with clinical expertise who understand the illness and issues with the treatment, it doesn’t need an entire panel of these people. She said that one way FDA can find more qualified experts is by looking at schools of public health where academics rarely get money from industry and they have expertise in understanding clinical trials as well as biostatics.

Even if the academic’s salary isn’t directly funded by their work with industry, there are multiple reasons to be concerned that work on industry trials with the same drugs creates conflicts.

“There’s research showing that researchers feel more positively about drugs that they’ve studied. That’s normal human behavior. You feel proprietary towards something that you’ve studied. You also have a relationship with the company,” said Adrian Fugh-Berman a professor Pharmacology and Physiology at Georgetown where she directs PharmedOut, a project that focuses on evidence-based prescribing and studying industry marketing practices.

The person may also be thinking about how their behavior on the committee may impact other research opportunities the university or they in particular have with the company, she explained.

“Are you going to get more research grants for the company if you kill their drug?” Fugh-Berman said.

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Over the past 12 months ODAC has had two other committee meetings where four waivers were granted but that is far from typical. Most agency advisory committees don’t have any waivers or at most have one or two, per data from FDA from 2018 onward.

FDA is supposed to publish an annual report to Congress on advisory committees that include information on waivers but the latest report available online was from fiscal year 2016. FDA did respond to questions about whether more updated data exists and where it can be found.

To read the entire article, see https://pink.pharmaintelligence.informa.com/PS144196/Conflicts-Galore-Upcoming-Accelerated-Approval-Cancer-Panel-Includes-Many-Industry-Relationships

FDA blasts Merck’s Keytruda data for new breast cancer indication

Ed Silverman, Stat News: February 5, 2021


Merck (MRK5 ) may have readily turned its Keytruda cancer drug into a medical and financial juggernaut, but its bid to win regulatory approval for at least one additional use may not come so easily, judging by documents from the Food and Drug Administration. The drug maker wants to sell the medicine to combat high-risk, early-stage triple-negative breast cancer along with chemotherapy before surgery, and then by itself after surgery.

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Given the FDA review, though, the likelihood of a recommendation next week is not high, according to Ira Loss of Washington Analysis, who tracks pharmaceutical regulatory and legislative matters for investors. “The agency believes, and we think the (FDA expert) committee will agree, that further data from the trial are needed to make an informed decision,” he wrote to investors.

Another FDA watcher was even more blunt. “It’s important to have good treatment because this disproportionately occurs among Black women,” said Diana Zuckerman, who heads the National Center for Health Research, a nonprofit think tank. “But they’re saying this may not be needed, may not work and may be harmful – that’s pretty damning. And there are some real safety issues that can have terrible impact on patients… This is one of the most negative reviews I’ve ever seen.”

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Read the full article here