[Updated 5/1/18, 12:34 p.m. See below.] Drug giant Bristol-Myers Squibb is the latest to feel the shockwave caused by the failure of a widely watched cancer immunotherapy nearly a month ago.
Xconomy has learned that Bristol (NYSE: BMY) is curtailing work on three late-stage studies testing an experimental cancer drug that it bought for $800 million three years ago.
The agent was an IDO inhibitor, part of a drug class considered a top contender to expand the limited reach of cancer immunotherapy. Earlier this month, epacadostat, an IDO inhibitor from Delaware biotech Incyte (NASDAQ: INCY), failed in combination with the FDA-approved pembrolizumab (Keytruda) in a major melanoma study.
Soon after that disclosure, NewLink Genetics (NASDAQ: NLNK) of Ames, IA, said it would curtail a Phase 3 combination study of its IDO inhibitor indoximod for melanoma “in the context of the failure of a competitor’s trial.”
Bristol’s disclosure is now the third domino to fall. It has terminated a study of its drug, BMS-986205, in head-and-neck cancer, and a separate study in non-small cell lung cancer has been withdrawn, according to records updated Monday in the clinicaltrials.gov database. Recruitment for the trials had barely begun. The head-and-neck cancer study had just one patient; the lung cancer study had none. But both studies list the same reason for the status update: “Business objectives have changed.”
A third Phase 3 study, testing BMS-986205 in melanoma, is listed as active but not recruiting new patients. Records show that 72 patients have been enrolled so far. Audrey Abernathy, a spokeswoman for Bristol’s immune-oncology division, said that the three late-stage studies were closed “based on emerging data on the IDO pathway.”
Bristol is continuing a fourth study, a Phase 1/2 test evaluating the drug in combination with two of its drugs in advanced cancers that have spread. Abernathy said this study is now the focus of Bristol’s IDO research.
Meanwhile, Incyte is pulling back on plans for additional studies of its IDO drug. In its report of first quarter financial results Tuesday, the company said that it would stop enrollment in six late-stage clinical trials. Four of those studies would have tested the Incyte drug in combination with Merck’s pembrolizumab; two others were planned with Bristol’s nivolumab. Incyte also said that it won’t start a Phase 3 study planned to test its drug in combination with an AstraZeneca drug. Furthermore, two late-stage studies testing Incyte’s drug with Merck’s will be converted to two randomized Phase 2 studies. [Paragraph added with additional information from Incyte.]
IDO is an enzyme produced by tumors that suppresses the body’s immune cells, enabling cancer cells to evade detection by the immune system. Drug developers have made big bets on IDO inhibitors as combination partners to boost the success rate of the first wave of immunotherapy drugs, which have a range of response rates under 50 percent, depending on the type of cancer. They include Merck’s pembrolizumab, Bristol’s nivolumab (Opdivo) and ipilimumab (Yervoy), and Roche’s atezolizumab (Tecentriq).
Bristol obtained its IDO inhibitor in 2015 when it plunked down $800 million to acquire much of the assets of San Carlos, CA-based Flexus Biosciences. At the time, Flexus had yet to start clinical tests for its drug, but the company had encouraging preclinical data.
Bristol’s Abernathy said the company has not given up on BMS-986205. It continues to study the drug in combination with both nivolumab and ipilimumab, the company’s checkpoint drugs, in cancers that have advanced or spread. According to clinical trial records, Bristol expects to enroll more than 900 patients in the study.
“We remain committed to continued research of BMS-986205-based combinations in an informed and scientifically robust manner,” Abernathy said.
Metastatic melanoma cells image by the National Cancer Institute