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Merck, Incyte IDO inhibitor fails late-stage trial

Result casts shadow over other similar-acting cancer immunotherapy drug candidates

by Lisa M. Jarvis
April 13, 2018 | A version of this story appeared in Volume 96, Issue 16

A high-stakes race among cancer immunotherapy drug developers has hit a roadblock. Merck & Co. and Incyte say a late-stage study combining Merck’s checkpoint inhibitor Keytruda with Incyte’s IDO inhibitor epacadostat to treat people with metastatic melanoma has failed.

The structure of epacadostat.

Epacadostat is one of a slew of compounds in development that block the activity of indoleamine 2,3-dioxygenase, or IDO, an enzyme that initiates the breakdown of tryptophan into metabolites that suppress the immune system. Researchers hypothesized that adding an IDO inhibitor to a checkpoint inhibitor, which takes the brakes off the immune system, could expand the number of patients who benefit from cancer immunotherapy.

Significant resources have been devoted to testing that hypothesis. Epacadostat is in dozens of studies, while IDO inhibitors from NewLink Genetics, Bristol-Myers Squib, and Eli Lilly & Co. are also advancing. At one point, analysts forecast multi-billion-dollar sales for epacadostat.

Meanwhile, biotech companies focused on IDO continue to emerge; just last month, Tempest Therapeutics secured $70 million in funding to support its IDO inhibitors.

The failure of the epacadostat-Keytruda trial has cast a shadow over all of those programs, especially since melanoma is considered the most likely tumor type to benefit from such combinations. Following the news, Incyte’s stock fell by more than 20%; NewLink saw its stock price tumble by roughly 45%.

Incyte CEO Hervé Hoppenot acknowledged that the disappointing result “has a negative impact on the probability of success” for other studies of epacadostat. Cowen stock analyst Eric Schmidt told investors that he hopes Incyte will “dramatically reduce, if not eliminate” its research budget for epacadostat.


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