Industry-wide accelerated approval review yields four withdrawals

Regulatory NewsRegulatory News | 10 March 2021 |  By 

Since late December, four drugmakers have voluntarily withdrawn indications for their cancer drugs amid an industry-wide review of accelerated approvals by the US Food and Drug Administration’s (FDA) Oncology Center of Excellence.
In each of their statements announcing the withdrawals, Bristol Myers Squibb, AstraZeneca, Merck and Roche said the withdrawal decisions were made in consultation with FDA as part of an industry-wide review of accelerated approvals with confirmatory trials that have not met postmarketing requirements (PMRs).
In a statement to Focus, an FDA spokesperson acknowledged the existence of the industry-wide review but declined to comment on the impetus for the review or its scope.
“The withdrawal decisions were made in consultation with the FDA and as part of a broader industry-wide evaluation by the FDA Oncology Center of Excellence. The FDA is currently in the process of evaluating oncology accelerated approvals and we will keep you updated when additional information becomes available,” the spokesperson said.
FDA’s accelerated approval program dates back to 1992 and is intended to speed the approval of drugs to treat serious conditions with unmet medical need based on their effect on a surrogate or intermediate clinical endpoint. Drugs granted accelerated approval are subject to PMRs to confirm their clinical benefit to be converted to regular approvals.
The agency has received criticism from researchers and the Government Accountability Office (GAO) for its oversight of products with accelerated approval, though FDA has defended the program and its ability to oversee PMRs. (RELATED: FDA Lacks Reliable, Accessible Postmarket Data on Drugs, GAO Says, Regulatory Focus 14 January 2016; Accelerated approval in oncology: FDA touts successes, responds to criticism, Regulatory Focus 5 March 2018; FDA should reassess postmarket trials for cancer drugs approved via accelerated pathway, researchers say, Regulatory Focus 28 May 2019).
While FDA may withdraw approval of drugs or indications with accelerated approval, the agency has rarely moved to do so on its own. Two notable examples include FDA’s decision to withdraw Avastin (bevacizumab) a decade ago and more recently its effort to pull Makena (hydroxyprogesterone caproate injection) from the market. (RELATED: FDA seeks withdrawal of Makena, generics from market, Regulatory Focus 5 October 2020).
Recently withdrawn accelerated approval indications
Company/Product Indication Accelerated approval Confirmatory studies Withdrawal announcement
Bristol Myers Squibb
Opdivo (nivolumab)
Treatment of patients with SCLC whose disease has progressed after platinum-based chemotherapy and at least one other line of therapy. August 2018 CheckMate -451
CheckMate -331
29 December 2020
Imfinzi (durvalumab)
Previously treated adult patients with locally advanced or metastatic bladder cancer. May 2017 DANUBE Phase III trial 22 February 2021
Keytruda (pembrolizumab)
Treatment of patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. June 2019 KEYNOTE-604 1 March 2021
Tecentriq (atezolizumab)
Prior-platinum treated metastatic urothelial carcinoma (mUC, bladder cancer). October 2016 IMvigor211
8 March 2021
The four recently withdrawn indications pertain to Bristol Myers Squibb’s Opdivo (nivolumab) and Merck’s Keytruda (pembrolizumab) in small cell lung cancer and AstraZeneca’s Imfinzi (durvalumab) and Roche’s Tecentriq in metastatic urothelial carcinoma (mUC). In all four cases, the drugs did not meet primary endpoints for overall survival in confirmatory studies. For Keytruda and Imfinzi, those results were reported in early 2020, while results for the two confirmatory studies for Opdivo were reported in 2018.
In the case of Tecentriq, the drug failed to meet its primary endpoint on overall survival in 2017, but FDA designated a second, still ongoing trial as a replacement PMR. While the results of that study on overall survival have not yet been reported, Roche said it decided to withdraw the indication “as the treatment landscape in prior-platinum (second-line) mUC has rapidly evolved with the emergence of new treatment options [and] in recognition of the principles of the accelerated approval program.”


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