RE:FDA offers clinical trial design on Accelerated ApprovalApril 08, 2024 - FDA's Richard Pazdur, M.D addressed some key topics at the FDA’s oncology department, including accelerated approval and confirmatory trial requirements, advisory committee meetings, some new regulatory initiatives. The FDA a few days ago issued two surprise complete response letters to Regeneron’s applications for accelerated approvals of its CD20xCD3 bispecific odronextamab in certain blood cancers. The action marked the first time a drug was rejected because of progress on confirmatory trials.
Pazdur said the FDA has been talking about the importance of having timely confirmatory studies for more than a decade. The agency recently gained the authority to require companies to have the confirmatory trial underway at the time of an accelerated approval—and to reject a drug if that prerequisite is not met—thanks to the Food and Drug Omnibus Reform Act of 2022.
Regeneron, for its part, supports the confirmatory trial reforms but told Fierce Biotech last week that industry needs more guidance on what exactly constitutes a confirmatory trial being “well underway.”
The decision for Regeneron was meant to level the playing field among drug developers, Pazdur explained during a fireside chat at the AACR event. Before odronextamab, the FDA has granted accelerated approvals to three other CD20xCD3 bispecifics, namely Roche’s Columvi for diffuse large B-cell lymphoma (DLBCL) and Lunsumio for follicular lymphoma, plus AbbVie and Genmab’s Epkinly in DLBCL.
When considering whether to issue a complete response letter, the OCE takes a patient-centric approach, Pazdur said. And that means possibly different rulings under different circumstances.
Regeneron’s proposed confirmatory studies had begun but only for the safety lead-in phase. Because the company is trying to move odronextamab into earlier treatment settings, the confirmatory trials were required to have an extra dose-finding phase before the actual randomized confirmatory efficacy portions begin.
The FDA these days wants drug companies to have discussions about their “comprehensive development plans,” including the confirmatory trial design, early on with the agency, Pazdur said.
“The exact number of [enrollment] needs to be discussed,” Pazdur added. “We also have to have confidence that the accelerated approval is not going to interfere with the completion of the trial or other accelerated approvals that may be reading out in the same disease, especially with the same class of drugs.”
https://www.fiercebiotech.com/biotech/we-have-have-level-playing-field-fda-oncology-chief-explains-confirmatory-trial-rejection