The Lancet July 22, 2022 on Accelerated approval n June, 2022, the US House of Representatives passed the first legislative reforms to the accelerated approval pathway since its creation by the US Food and Drug Administration (FDA) in 1992 during the HIV/AIDS epidemic.
Although the FDA has increasingly used accelerated approval (with 278 accelerated approvals from 1992 to 2021), this pathway has been controversial, particularly because of these drugs' high cost, uncertain efficacy, and absence of completed confirmatory studies. For example, aducanumab received accelerated approval for Alzheimer's disease despite a negative pivotal trial and the advisory committee voting against approval. This accelerated approval resulted in a 14% initial increase in Medicare Part B insurance premiums this year.
In exchange for earlier market access, sponsors are expected to conduct postapproval studies to confirm clinical benefit. However, most postapproval studies have been delayed or not completed, and, until recently, accelerated approval was not often withdrawn when confirmatory studies failed.
In a recent initiative, sponsors of several cancer medicines have voluntarily withdrawn accelerated approvals with negative postapproval studies.
Without such cooperation from the sponsor, withdrawal of accelerated approval by the FDA has been protracted and exceedingly rare—bevacizumab for metastatic breast cancer is the only non-voluntary withdrawal to date.
The Food and Drug Amendments of 2022 grant the FDA explicit legal authority to require initiation of confirmatory studies prior to accelerated approval, setting of enrolment targets, and biannual (twice yearly) reporting of study progress. The legislation also codifies an expedited withdrawal procedure that can be triggered if the sponsor fails to conduct the required postapproval study, the confirmatory study does not confirm benefit, other evidence shows the product is not safe and effective, or the sponsor disseminates false or misleading promotional materials.
These provisions are important reforms to the accelerated approval programme, which we believe could be further modernised. In addition to study progress reporting, the FDA could require an annual review of the overall benefit–risk balance of accelerated approvals (as is done by the European Medicines Agency for conditional marketing authorisation). In addition, as underscored by the aducanumab approval (for which <1% of study participants were Black), the FDA could make accelerated approval conditional on adequately inclusive clinical trials, and, if such studies are not completed before approval, the FDA should require that successful completion of postapproval requirements is defined as enrolment of participants representative of the national disease population. Ultimately, these reforms would advance timely evidence generation, the safety of medications available on the market, and equity in clinical trials for medicines receiving accelerated approval.