Lexington, Mass.-based Agenus withdrew its Biologics License Application for balstilimab from the U.S. FDA. The drug is a PD-1 inhibitor or checkpoint inhibitor.
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Lexington, Mass.-based Agenus withdrew its Biologics License Application (BLA) for balstilimab from the U.S. Food and Drug Administration (FDA). The drug is a PD-1 inhibitor or checkpoint inhibitor.
The FDA had recently granted full approval to Merck’s own blockbuster checkpoint inhibitor, Keytruda (pembrolizumab), for the same indication, and the agency recommended Agenus withdraw the application. Agenus’s BLA was being reviewed under an Accelerated Approval pathway as well as Fast Track and Priority Review designations. The target action date was December 16, 2021.
Agenus indicates it plans to continue its development strategies for balstilimab in combination with other drugs.
Merck’s Keytruda was granted accelerated approval in second-line cervical cancer in 2018. Then, in mid-October, the FDA granted it first-line approval with chemotherapy, with or without bevacizumab, for persistent, recurrent or metastatic cervical cancer. The trial was not only for first-line advanced cervical cancer but also a confirmatory trial for the accelerated approval, allowing the agency to convert the accelerated approval over to a standard approval.
“While the commercial market for balstilimab monotherapy in second-line cervical cancer was always anticipated to be small, Agenus’ priority remains developing balstilimab as a necessary component of highly effective and affordable combination therapies, both with its own portfolio and with partners, including in combination with Agenus’ next-generation CTLA-4, AGEN1181,” said Garo Armen, chief executive officer and chairman of Agenus.
Agenus plans to discontinue its ongoing confirmatory trial. Shares plunged 22% to $3.98 in premarket trading today at the news. It is also expected to decrease its research and development expenses by more than $100 million due to the shift.
Because the drug has demonstrated clinical benefit, the company is considering launching an expanded access program that would allow patients and doctors access to the drug in several countries, including the U.S.
Although the company statement indicates it is voluntarily withdrawing the BLA, reporting suggests the company is not happy with the decision and that Armen has written to the FDA’s Richard Pazdur, director of the FDA’s Oncology Center of Excellence for the Center for Drug Evaluation and Research, to intervene.
“This seemingly quick approval of pembrolizumab (Keytruda) hours before Agenus’s late-cycle meeting suggests that FDA may have afforded special consideration to Merck, the sponsor of the pembrolizumab application,” Armen wrote to Pazdur. “The fact that pembrolizumab’s approval blocked Agenus’s chances of accelerated approval further implies that FDA was not intending to afford balstilimab the full and fair review that it deserves.”
There have been suggestions that the FDA is getting tougher on accelerated approvals. They are usually granted for drugs with a high unmet need but require the companies to run post-marketing studies to determine if the drugs are as effective as they seem to be in earlier trials. Accelerated approvals are typically based on surrogate endpoints, such as biomarker readouts, rather than a specific clinical benefit.
Several accelerated approvals have been rescinded this year and some unexpected rejections to support the argument that the agency is getting tougher on accelerated approvals. On March 1, Merck voluntarily withdrew the U.S. indication for Keytruda for metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least one other previous line of therapy. And before that, AstraZeneca had withdrawn its own checkpoint inhibitor Imfinzi in bladder cancer over a similar response.
Steven O’Day, Agenus’s chief medical officer, stated, “Balstilimab has demonstrated meaningful clinical activity and an excellent safety profile in second-line cervical cancer, including the PD-L1 negative patients, who are ineligible to receive standard of care anti-PD-1 therapy, which makes the decision to withdraw so difficult for us. Balstilimab remains a critical component of our combination regimens, including with our next-generation CTLA-4 agent, AGEN1181. Concomitant with presentation of new data at SITC next month, we continue to accelerate development of AGEN1181 in combination with balstilimab in trials designed to rapidly support full or accelerated approval in multiple tumor types.”
