FDA Denies Fast-Track Approval for Agenus' Colorectal Cancer Drug

The U.S. Food and Drug Administration (FDA) has provided guidance on the phase 3 dosing regimen for Agenus' BOT/BAL immunotherapy combination, intended for patients with relapsed/refractory microsatellite stable colorectal cancer (r/r MSS CRC). However, the FDA has recommended against pursuing accelerated approval for this treatment, as per the company's recent announcement.

Agenus has been advised by the FDA to include a BOT monotherapy arm in its phase 3 study. This suggestion follows interim results from the phase 2 trial, which demonstrated an overall response rate (ORR) of 19.4% and a six-month survival rate of 90%, results that are in line with those observed in the phase 1 trial. Agenus aims to present the complete phase 2 data at an upcoming medical conference.

In tandem with its efforts in the U.S., Agenus is also planning to engage with the European Medicines Agency (EMA) in the third quarter of 2024. The purpose of this meeting is to discuss potential approval pathways for the BOT/BAL combination therapy in Europe. Furthermore, the company is extending the development of BOT/BAL to treat other types of cancer, such as lung, melanoma, and pancreatic cancers.

The BOT/BAL combination comprises two immunotherapy agents: botensilimab (BOT) and balstilimab (BAL). Botensilimab functions as a CTLA-4 blocking antibody, which is designed to boost both innate and adaptive anti-tumor immune responses. This is achieved through the activation of T cells, the reduction of regulatory T cells within tumors, the activation of myeloid cells, and the induction of long-term memory responses. On the other hand, balstilimab is a PD-1 antibody that works by enhancing the immune response against cancer. It achieves this by blocking the PD-1 pathway, a mechanism that tumors often exploit to escape immune detection.

By integrating these two agents, the BOT/BAL combination aims to provide a robust anti-tumor response. The strategy behind using both a CTLA-4 blocker and a PD-1 inhibitor is to simultaneously enhance different components of the immune system, thereby offering a comprehensive approach to fighting cancer.

The phase 3 study's inclusion of a BOT monotherapy arm, as recommended by the FDA, will provide additional data to understand the individual contributions of botensilimab to the overall efficacy of the combination treatment. This step is crucial for determining the most effective dosing regimen and understanding the full therapeutic potential of BOT when used alone, compared to its use in combination with BAL.

Agenus' proactive approach in seeking regulatory guidance and exploring approval pathways in both the U.S. and Europe signifies its commitment to advancing the BOT/BAL therapy. The company is poised to contribute significantly to the treatment landscape for colorectal cancer and potentially other cancer types, pending successful outcomes from ongoing and future clinical trials.

Overall, the guidance from the FDA and the planned discussions with the EMA reflect the rigorous process of ensuring that new therapies meet safety and efficacy standards before they become widely available to patients. Agenus' BOT/BAL combination holds promise, and its future developments are eagerly anticipated in the medical community.