Ponatinib: Accelerated Disapproval.

Drug development for life-threatening diseases is still a process in evolution. In oncology, as drugs have become more targeted, the regulatory path to drug approval has shortened, with increasing reliance on the Accelerated Approval pathway to provide early access to active agents. However, this approach is not without risks, as illustrated by the recent experience with ponatinib, a promising agent in chronic myeloid leukemia (CML). In 1992, responding to the need for rapid access to antiHIV medication, Congress passed legislation creating a new pathway for early drug approval, called “Accelerated Approval” (AA). From its inception, this approval was considered conditional because it relied on a surrogate endpoint, such as response rate, that was considered “reasonably likely to predict a clinical benefit.” The law required further proof of safety and efficacy in postmarketing trials, because neither could be fully understood at the time of AA. Nonetheless, AA fulfilled the need to provide promising new medications for serious or potentially fatal conditions. AA has proven to be a welcome regulatory innovation— especiallywithin oncology.More than 40 anticancer agents have thus fargainedAA. In2014alone, fullyonequarterofallFoodand Drug Administration (FDA) approvals in hematology/oncology were granted via the accelerated pathway. In an analysis of oncology products granted AA between 1992 and 2010, the median time from AA to full approval was 3.9 years, underscoring the importance of AA in providing early access to promising anticancer agents [1]. Despite this positive impact on drug development, challenges remain.