The FDA has scotched Agenus’ plans to seek accelerated approval for a colorectal cancer combination, prompting the biotech to look into partnering to fund the phase 3 required to reach the market. Shares in Agenus fell 38% to around $11 in premarket trading.
Agenus went all in on the combination of its CTLA-4 blocking antibody botensilimab and PD-1 candidate balstilimab to cut costs last year. At the end of phase 2 meeting, Agenus aimed to get alignment with the FDA on the design of the planned confirmatory trial. The plan was to get the study underway in time to support an application for accelerated approval, based on the phase 2 results, by the end of the year.
The meeting provided the hoped-for alignment on the phase 3 dose. Beyond that, Agenus had little to cheer coming out of the meeting with the FDA, primarily because the agency advised against filing for accelerated approval on the basis of the existing data.
Agenus said the FDA discouraged a filing for accelerated approval because of its belief objective response rates may fail to translate into survival benefit. The response rates seen in interim phase 2 data were key to Agenus’ filing plan. The biotech linked the most effective dose of botensilimab and balstilimab to a 19.4% response rate, compared to 0% in the standard-of-care cohort.
In phase 1, Agenus saw a 23% response rate that translated into an estimated median overall survival of 21.2 months. The biotech made the estimate after a median of 13.6 months of follow-up. The median follow-up in the phase 2 cohorts ranges from 5.5 months to 9.5 months. At 90%, the six-month survival rate at the preferred dose in the phase 2 trial is in line with the results of the earlier study.
The phase 2 data are immature, though. And while Agenus plans to keep talking to the FDA as the data matures, the company faces the prospect of having to run a phase 3 study before it can seek approval. Steven O’Day, Agenus’ chief medical officer, said the biotech’s commitment to exploring ways to get the combination to patients is “unwavering” and will drive it to look to partner the program in the U.S.
Any company that takes on the program will receive a wish list from the FDA that includes enrollment of a CTLA-4 monotherapy arm in the phase 3 study. The inclusion of the arm is at “Agenus’ discretion,” the biotech said.