Accelerated approval for oncology drugs successful, but improvements needed

Johnson JR. J Natl Cancer Inst. 2011;doi:10.1093/jnci/djr062

Issue: May 10, 2011

In the past 18 years, 47 new indications for 35 oncology drugs received accelerated approval from the FDA. In addition, post-approval trials have confirmed the benefits of more than half of these drugs, according to a review article published online.

“The accelerated approval process has been successful in making promising new drugs available to cancer patients sooner than they would have been if they had undergone regular approval,” the researchers said.

Using FDA databases, the researchers identified drug and biological products that received accelerated approval between Dec. 11, 1992, and July 1, 2010. Drugs that appear to have benefit over available therapies are eligible for accelerated approval. Once granted accelerated approval, post-approval trials must confirm the clinical benefits of the drug based on a surrogate endpoint. If such a trial is not conducted with due diligence, the drug may be removed from the market.

According to the researchers, 35 oncology drugs received accelerated approval for 47 new indications; post-approval trials confirmed clinical benefit for 26 of the 47 new indications and received regular approval. Nineteen of the 47 accelerated approvals were based on randomized comparative trials and 28 were based on single-arm trials.

The median time between accelerated and regular approval was 3.9 years (range, 0.8-12.6 years) and the average time was 4.7 years. According to the researchers, the time savings to provide patients with drugs earlier was substantial.

Of the 21 drugs not converted to regular approval, three have failed to demonstrate confirmed clinical benefit in post-approval trials, 14 have not completed post-approval trials and four are currently under FDA review. “The due diligence in conducting post-approval trials to confirm clinical benefit has been suboptimal,” the researchers said.

Their results demonstrate that the five longest time intervals from accelerated approval designation to the study cutoff date (July 1, 2010) were 10.5, 6.4, 5.5, 5.5 and 4.7 years. The five longest intervals from accelerated approval to regular approval were 12.6, 9.7, 8.1, 7.5 and 7.4 years.

“Because of the possibility that confirmatory trials will not confirm clinical benefit, indications that have received accelerated approval should not be on the market for unacceptably prolonged intervals in the absence of completed trials to confirm clinical benefit,” the researchers said.

In an accompanying editorial, Susan S. Ellenberg, PhD, of the University of Pennsylvania School of Medicine, said such analyses are essential to improve the regulatory process. In addition, the FDA’s new regulatory science initiative announced last fall “should support more in-depth analyses of regulatory data that could provide valuable insights regarding optimization of regulatory approaches.”

“Trials to confirm clinical benefit should be part of the drug development plan and should be in progress at the time of an application seeking accelerated approval to prevent an ineffective drug from remaining on the market for an unacceptable time,” the researchers said.

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