Agenus faces challenges as FDA advice on cancer drug combo hits stock

Agenus shares experienced a significant drop of over 54% on Thursday following the announcement that the FDA had "discouraged" the company's plan to seek accelerated approval for an immunotherapy combination targeting microsatellite stable colorectal cancer (MSS CRC), which is the most common form of the disease. This setback impacts Agenus' strategy involving a combination of botensilimab, an Fc-enhanced anti-CTLA-4 antibody, and the PD-1 inhibitor balstilimab for patients with relapsed or refractory disease.

The market's negative reaction was fueled by Agenus' disclosure of the outcomes from its end-of-Phase II meeting with the FDA. During this meeting, the agency advised against submitting the recent trial results in an attempt to secure a fast-tracked approval for the treatment regimen. The FDA's position was based on the notion that the observed objective response rates (ORRs) may not necessarily lead to a survival benefit.

Topline interim data from the ongoing Phase II trial, as reported by Agenus, showed trends that were in line with the earlier Phase I results. In the group receiving the agreed-upon Phase III dose (BOT 75 mg/BAL 240 mg), the company reported an ORR of 19.4% after a median follow-up of 9.5 months, with a six-month survival rate of 90%, and the data continues to mature. For patients receiving an increased BOT dose of 150 mg, the combination therapy was associated with an ORR of 8.2%.

Earlier this year, a 77-patient Phase I study had shown a 23% ORR with the same regimen after a median follow-up of 13.6 months, with an estimated median overall survival of 21.2 months. Similar to the Phase II trial, the Phase I study also included refractory MSS CRC patients without active liver metastases.

Steven O'Day, the chief medical officer at Agenus, affirmed on Thursday that the company remains committed to the program despite the regulatory challenges. O'Day stated, "Based on the high level of enthusiasm from significant numbers of global clinical experts and the promising clinical activity we have seen in the Phase I and II studies, our commitment to seek all possible pathways to make BOT/BAL available to patients is unwavering." He also mentioned that the company is exploring opportunities to partner within the US to accomplish a successful Phase III trial.

The FDA has suggested including a BOT monotherapy arm "at Agenus' discretion" in the Phase III study. The mid-stage results released on Tuesday indicated an ORR of 7.5% for BOT monotherapy at 150 mg, but there was no response at the 75-mg dose.

Meanwhile, Agenus is advancing its efforts to make BOT/BAL available to patients in Europe, with plans to discuss possible registration paths later this summer.