Accelerated approval drugs effective, but status did not speed development

Returning to endorsing phase-2 designs for FDA accelerated approval may shorten approval time.

FDA accelerated approval of oncology new molecular entities has been insufficient, as approval times are not shorter than standard approval times, according to a study published in The Journal of Clinical Oncology. An emphasis is still being placed on phase-3 trial designs for both regular and advanced approvals, and the percentage of new molecular entities receiving advanced approval has decreased since 2003.

“We conclude that the promise of accelerated approval is not being met,” researchers wrote.

Elizabeth A. Richey, MD, of the division of hematology/oncology, Feinberg School of Medicine, and colleagues examined data from oncologic new drug applications approved by the FDA between 1995 and 2008. Data on development time, safety and status of confirmatory trials of accelerated approvals were analyzed.

Since the first accelerated approval for an oncology drug in 1995, 19 new molecular entities received accelerated approval and 32 new molecular entities received regular approval.

There was little difference between development times, with the median development time for drugs with accelerated approval at 7.3 years and the development time for those with regular approval at 7.2 years.

Accelerated approvals accounted for 78% of new molecular entity approvals between 2001 and 2003 but accounted for only 32% from 2004 to 2008. Fifty-three percent of oncology new molecular entities that received regular approval and 63% that received advanced approval were for orphan drug indications.

Efficacy findings were supported by phase-3 trials in 75% of regular approvals compared with 26% of accelerated approvals of oncology new molecular entities.

Among new molecular entities that received accelerated approval, those that were for orphan drugs were nine times less likely to confirm clinical benefit (95% CI, 0.02-0.63) than non-orphan accelerated approvals. The median duration between granting advanced and regular approval was 2.1 years for orphan drugs and 3.7 years for non-orphan drugs.

After approval, black box warnings were added to package inserts for four (17%) of oncology new molecular entities that received accelerated approval, and three black box warnings were added to two (9%) of oncology new molecular entities that received regular approval.

Richey EA. J Clin Oncol. 2009;doi:10.1200/JCO.2008.21.1961.