FDA Derails Agenus’ Accelerated Approval, Prompting Cancer Combo Partnership Push

Agenus' strategy to secure accelerated approval for its colorectal cancer treatment combination has hit a roadblock, as the FDA has advised against proceeding with the current data. This setback has led the biotech company to consider partnerships to fund the necessary phase 3 trials for market entry. Consequently, Agenus shares plummeted by 38%, reaching approximately $11 in premarket trading.

Last year, Agenus focused its efforts on the combination of its CTLA-4 blocking antibody botensilimab and its PD-1 candidate balstilimab to reduce costs. The company had aimed to align with the FDA on the design of a planned confirmatory phase 3 trial during an end-of-phase 2 meeting. The goal was to initiate this study in time to support an accelerated approval application based on phase 2 results by the end of the year.

The meeting with the FDA did yield alignment on the phase 3 dosage, but little else went as hoped. The FDA recommended against filing for accelerated approval due to concerns that the objective response rates observed might not translate into a survival benefit. Agenus had based its filing plan on the interim phase 2 data, which showed a response rate of 19.4% for the most effective dose of the drug combination, in contrast to a 0% response rate in the standard-of-care cohort.

In phase 1 trials, Agenus had observed a 23% response rate that correlated with an estimated median overall survival of 21.2 months, based on a median follow-up of 13.6 months. The median follow-up in the phase 2 cohorts ranges between 5.5 to 9.5 months. At 90%, the six-month survival rate at the preferred dose in the phase 2 trial mirrors the earlier study's results.

However, the phase 2 data remains immature. Though Agenus plans to continue discussions with the FDA as the data evolves, the company may need to conduct a phase 3 study before seeking approval. Steven O’Day, Agenus’ chief medical officer, emphasized that the biotech's commitment to bringing the combination treatment to patients is "unwavering," and the company will explore partnerships to advance the program in the U.S.

Any potential partner taking on the program would need to address the FDA's requirements, including the enrollment of a CTLA-4 monotherapy arm in the phase 3 study. The inclusion of this arm, however, is left to Agenus' discretion.

In summary, Agenus faces significant challenges ahead, requiring additional clinical trials and potential partnerships to bring its promising colorectal cancer treatment to market. Despite the current hurdles, Agenus remains steadfast in its mission to deliver this combination therapy to patients in need.