- Shares of Agenus, a Massachusetts-based biotechnology company, fell around 22% Friday morning after the company announced plans to withdraw an application that could have gotten one of its most closely watched drugs approved in the U.S.
- Agenus' drug is designed to fight cancer by alerting the immune system to the presence of malignant cells. Specifically, it blocks the activity of PD-1, a protein that stifles the body's immune response and that has been a prominent target for cancer drugmakers. To date, the Food and Drug Administration has approved seven medicines targeting PD-1 or the related PD-L1, including Bristol Myers Squibb's Opdivo, Roche's Tecentriq and Merck & Co.'s Keytruda.
- Agenus aimed to get its drug approved for cervical cancer that had returned or spread after chemotherapy. The FDA had agreed to speedy review — a regulatory advantage typically offered when a drug is developed for a disease with insufficient treatment options. But according to Agenus, the agency has since recommended the company withdraw its application in light of the recent approval of Keytruda for the same indication.
Keytruda ranks as one of the world's most profitable drugs. In just the three months from July to September, it brought in more than $4 billion for Merck — a commercial success that reflects just how many types of cancer Keytruda treats. Since first coming to market in 2014, the drug has won more than two dozen FDA approvals.
On Oct. 13, Keytruda received yet another approval, this time in combination with chemotherapy and potentially Avastin for patients with hard-to-treat cervical cancer whose tumors test positive for the PD-1 protein. Cervical is the fourth most commonly diagnosed cancer in women in the U.S.
The decision allowed Keytruda to be used as an initial, "first-line" treatment and, importantly, upgraded to full approval an accelerated OK from 2018 that had cleared the drug for cervical cancer patients whose disease had progressed following chemotherapy. Keytruda is currently the only PD-1 drug approved in cervical cancer.
Agenus had hoped its drug, known as balstilimab, could provide another, potentially better option in the "second-line" setting. While comparing clinical trial results can be tricky, the company notes how, among 140 evaluable patients in a single-arm study evaluating balstilimab as a second-line treatment, tumors shrunk in 20% of patients who were positive for the PD-1 protein and 8% of those who were negative.
Conversely, the study that led to Keytruda's initial approval as a second-line cervical cancer treatment found that tumors shrank in 14% of patients with the PD-1 protein and 0% of those without it.
"Balstilimab has demonstrated meaningful clinical activity and an excellent safety profile in second-line cervical cancer, including in 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," said Steven O'Day, chief medical officer at Agenus, in an Oct. 22 statement.
Agenus noted that the decision does not change its plans to develop balstilimab in combination with other drugs. The company is sponsoring studies that pair balstilimab with experimental Agenus medicines targeting other proteins of interest to cancer research, including CTLA-4 and CD137.
Yet, the withdrawal does mean Agenus will discontinue an ongoing confirmatory trial testing balstilimab in patients with cervical cancer that has spread or returned after chemotherapy. The company expects ending that trial will reduce research and development expenses by more than $100 million. Last year, Agenus spent $143 million on R&D.
However, Agenus intends to launch an expanded access programs so patients and doctors can access balstilimab in the U.S. and several other countries.
Agenus shares traded at $4.04 at market's open Friday, but fell further in the morning.