The FDA's oncology department, led by Richard Pazdur, M.D., is adopting a stricter stance on accelerated approvals for cancer drugs, requiring companies to have confirmatory trials well underway before a therapy is granted accelerated approval. This shift aims to ensure that confirmatory evidence is generated more rapidly, reducing the time between initial approval and either confirmation of efficacy or market withdrawal.
Pazdur highlighted the importance of having a comprehensive plan for confirmatory studies early in the development process. The FDA now expects companies to discuss these plans upfront and ideally have confirmatory trials underway when submitting their applications for accelerated approval.
This policy change is expected to significantly impact how biopharmaceutical companies, particularly smaller ones, approach cancer drug development. Previously, some companies relied on accelerated approvals based on single-arm trials in heavily pretreated patients as a pathway to commercialization. These companies would then use the initial approval to secure funding for larger, randomized trials. The FDA's new requirement for early confirmatory trials may alter this business model.
The FDA's increased focus on confirmatory trials stems from concerns about the time elapsed between accelerated approval and either confirmation of efficacy or market withdrawal. According to an article in the New England Journal of Medicine by Pazdur and colleagues, oncology drugs withdrawn under the accelerated approval pathway took a median of 7.3 years for withdrawal if the confirmatory trial wasn't ongoing at the time of approval, compared to 3.8 years if the study was already underway. Pazdur emphasized that the agency is trying to address this "period of vulnerability."
ADC Therapeutics recently experienced a delay in its application for accelerated approval of camidanlumab in relapsed or refractory Hodgkin lymphoma because the FDA wants its phase 3 confirmatory study to be "well underway and ideally fully enrolled" before filing. Similarly, Regeneron has pushed back its timeline for CD20xCD3 bispecific antibody odronextamab in certain lymphoma types, citing the FDA’s focus on having phase 3 trials “substantially enrolled” at the time of submission, according to CEO Len Schleifer, M.D., Ph.D.
While the FDA can be flexible with breakthrough therapies, it will be stricter with drugs that are not considered highly innovative. Pazdur emphasized that companies should understand where their drug falls in this spectrum during initial discussions with the FDA. The goal is to avoid situations where no patients are enrolled in a confirmatory trial at the time of an accelerated approval application.
The FDA's primary concern is ensuring patient benefit, and accelerated approval is not intended as an incentive program for the industry. While some worry that this policy will hurt innovation, Pazdur believes that small biotechs with truly innovative drug programs will be able to find financial support to advance confirmatory trials by partnering with established pharmaceutical companies.
