Bristol-Myers Squibb hammered another nail in the coffin of IDO1 as a drug target in immuno-oncology yesterday after halting two trials of its BMS-986205 candidate acquired via its $1.2bn purchase of Flexus Biosciences in 2015.
Enrolment has been suspended in trials of BMS-986205 in non-small cell lung cancer and head and neck cancer, while a third study in melanoma is still officially active but has only recruited a portion of the patients expected. The company said in a statement it “is important to follow the science to make decisions that will result in clinically meaningful outcomes for patients”, according to Xconomy.
The failure of Incyte’s IDO1 inhibitor epacadostat in a trial pairing it with Merck & Co/MSD’s PD-1 inhibitor Keytruda (pembrolizumab) last month seems to have started a chain reaction of negative news about the category, and obliterated enthusiasm for what was previously one of the hottest targets in immuno-oncology.
The Incyte trial failure was swiftly followed by a decision by NewLink Genetics to review the status of its own IDO1 programme, headed by indoximod and NLG802, and the company later said it wouldn’t progress a combination study with Bristol-Myers Squibb’s PD-1 inhibitor Opdivo (nivolumab) in melanoma.
BMS is bailing out on its late-stage programme for BMS-986205, but is sticking with earlier-phase combination studies, including seven phase I and II trials that variously see the IDO1 inhibitor given alongside Opdivo, BMS’ CTLA4 inhibitor Yervoy (ipilimumab), other marketed cancer drugs and LAG-3 candidate relatlimab.
Shortly after BMS’ announcement, Incyte added to the desultory picture by confirming on its first-quarter results call that enrolment is being halted in two pivotal trials of epacadostat and Opdivo and four trials pairing the drug with Keytruda. Meanwhile another study of epacadostat with AstraZeneca’s PD-L1 inhibitor Imfinzi (durvalumab) will also not go ahead.
Like BMS it is continuing to look at combinations of its drug with Keytruda in non-small cell lung cancer (NSCLC) as well as other combinations with drugs other than PD-1/PD-L1 inhibitors, but the drug has been firmly relegated to speculative status. Analyst Liisa Bayko of JMP Securities said that she has now removed the epacadostat programme from her calculations for the company.