- Delaware-based biotech Incyte will substantially scale back development of its IDO inhibitor epacadostat, stopping enrollment into six pivotal combination studies following the damaging failure last month of a Phase 3 trial involving the cancer immunotherapy.
- Incyte's decision, announced Tuesday, largely curtails two major clinical collaborations Incyte struck with Merck & Co. and Bristol-Myers Squibb to explore whether adding epacadostat could boost the effectiveness of the companies' respective PD-1 inhibitors Keytruda and Opdivo.
- The downsizing of Incyte's clinical program, while not entirely unexpected, is another signal of the dimming prospects for research into IDO inhibition more broadly. Following disappointing data from Incyte's ECHO-301 study, Bristol-Myers separately closed studies of its own IDO inhibitor in melanoma, lung, and head and neck cancers.
Attracted by positive signs from early studies of epacadostat, drugmakers like Merck and Bristol-Myers had billed IDO inhibition as a potentially complementary partner to checkpoint blockers — part of a larger quest to find effective immunotherapy combinations.
Incyte's ECHO-301 study was the first real litmus test of whether adding epacadostat could be proven to drive greater benefit than PD-1/L1 inhibitors alone. But results, released in early April, showed combining epacadostat with Keytruda (pembrolizumab) had no effect on progression-free survival in melanoma patients versus Keytruda monotherapy.
It was a damaging setback that has since sent ripple effects throughout the IDO field, while raising questions about how best to combine immunotherapies. Incyte rival Newlink Genetics soon after dropped plans to advance its similar drug indoximod into randomized testing in melanoma.
"These setbacks in the IDO1 inhibitor class could also have broad implications for other immuno-oncology agents under development that do not have single agent activity and are built on the promise of potential synergy with checkpoint blockade," wrote Leerink analyst Geoffrey Porges in a May 2 note to investors.
Per its plans announced Tuesday, Incyte will discontinue enrollment into four pivotal studies testing epacadostat with Merck's Keytruda in bladder, kidney and head and neck cancers. Two trials pairing Incyte's drug with Bristol-Myers Opdivo (nivolumab) will also stop enrollment, and patients currently in all six studies will have the option to consider therapeutic alternatives.
Clinical programs scaled back after ECHO-301 setback
|Combination||Cancer type||Trial name||Status|
|Epacadostat + Keytruda||Melanoma||ECHO-301||Failed, study stopped|
|Epacadostat + Keytruda||Renal cancer||ECHO-302||Enrollment to be discontinued|
|Epacadostat + Keytruda||Bladder cancer||ECHO-303 & -307||Enrollment to be discontinued|
|Epacadostat + Keytruda||Head & neck cancer||ECHO-304||Enrollment to be discontinued|
|Epacadostat + Keytruda||NSCLC||ECHO-305 & -306||Converted into Phase 2 studies|
|Epacadostat + Opdivo||NSCLC||ECHO-309||Enrollment to be discontinued|
|Epacaodstat + Opdivo||Head & neck cancer||ECHO-310||Enrollment to be discontinued|
|Epacadostat + Imfinzi||NSCLC||Pacific-3||Will not be initiated|
SOURCE: Incyte Corp.
A Phase 3 study involving epacadostat and AstraZeneca's PD-L1 blocker Imfinzi (durvalumab), which was scheduled to begin shortly, will not be initiated.
Incyte will continue limited research of epacadostat, converting what were supposed to be pivotal studies of epacadostat and Keytruda in lung cancer to randomized, Phase 2 trials.
"We will continue to investigate the potential utility of IDO1 inhibition in a variety of clinical settings, but these will be conducted in small proof-of-concept trials and where we believe the biology and translational data are compelling," said Incyte's Chief Medical Officer Steven Stein on a May 1 earnings call.
Separately, Bristol-Myers decided to stop several studies testing an IDO inhibitor, called BMS-986205, that it had acquired from Flexus Biosciences for $800 million upfront in 2015.
"Based on the Incyte announcement as well as data from our own IDO program, we are rationalizing our overall IDO program, ensuring we prioritize resources across the portfolio," said Bristol-Myers CEO Giovanni Carforio on an April 26 earnings call with analysts.
A spokesperson for the pharma said research of combinations involving BMS-986205 would continue, including a Phase 1/2 study called CA017-003 that pairs the drug with Opdivo and Yervoy (ipilimumab).