Postmarket Trial Failures Lead Some Sponsors to Withdraw Cancer Drugs from the Market
Only about half of oncology drug sponsors granted accelerated approval by the FDA complete postmarket trial requirements the agency sets, and some sponsors have withdrawn products from the market recently in the face of an ongoing FDA review of the accelerated approval program.
In a June 2018 review of all accelerated approvals granted for malignant hematology and oncology indications from the program’s inception to May 2017, the FDA found that 40 percent of indications had not finished confirmatory trials or verified clinical benefit at that point. Out of the 93 accelerated approvals, 51 (55 percent) met their postmarket requirement and verified the product’s benefit in a median of 3.4 years after the initial approval was given.
Last week, Roche withdrew the bladder cancer indication for Tecentriq (atezolizumab) after its late-stage trial failed to meet its primary endpoint of overall survival in PD-L1-high patients. The company described its withdrawal as being motivated by “an industrywide review of Accelerated Approvals with confirmatory trials that have not met their primary endpoint(s) and have yet to gain regular approvals.” The FDA granted Tecentriq Accelerated Approval in 2016.
In another example, at the end of December 2020, Bristol Myers Squibb withdrew its indication for Opdivo (nivolumab) for treating small-cell lung cancer (SCLC) patients whose disease has progressed after platinum-based chemotherapy and at least one other therapy. Opdivo had won accelerated approval for SCLC in 2018 based on its effect on surrogate endpoints from a phase 1/2 trial, but its later confirmatory studies didn’t meet primary endpoints of overall survival as required.