- Incyte Corp. and partner Merck & Co. will stop a closely watched cancer combination study, admitting failure after a data monitoring committee reported the pairing of Incyte's IDO inhibitor epacadostat and Merck's Keytruda showed no significant benefit in treating advanced melanoma.
- Adding epacadostat to treatment with Keytruda did not improve progression-free survival versus Keytruda alone, according to topline results disclosed by the companies April 6. Data also indicated the combination was unlikely to improve overall survival, the study's secondary objective.
- Shares in Incyte fell sharply on the news, which call into question a wide-ranging clinical program launched by Incyte and Merck on the potential of epacadostat as a partner for anti-PD-1 checkpoint inhibition.
Results from Incyte and Merck's study, called ECHO-301, will likely cool interest in epacadostat, and possibly in IDO inhibition more broadly.
Merck, along with rival Bristol-Myers Squibb Co., had previously inked major clinical collaborations with Incyte, lured by promising, single-arm results that suggested adding epacadostat could improve patient response to treatment with checkpoint inhibitors.
An update last September, which showed an overall response rate of 56% to Keytruda plus epacadostat, had further raised hopes in ECHO-301's success.
Data from the study, however, clearly show that, in melanoma at least, epacadostat didn't live up to expectations.
On progression-free survival, the combination of Incyte's drug and Keytruda failed to deliver any benefit versus Keytruda alone, notching a hazard ratio of 1.00. Review by the external data monitoring committee showed a similarly disappointing effect on overall survival, although that analysis remained premature.
Incyte executives said on a call Friday they planned to study the data further, but acknowledged the results seen in melanoma lowered expectations for the combo in other cancer types.
"[The hazard ratio] leaves no doubt that in this study against pembrolizumab, the compound didn't perform," said Steven Stein, Incyte's chief medical officer, on an April 6 call with analysts. "Given those hazard ratios, it is going to be difficult to discern a subgroup with sufficient effect."
Incyte said time remained to make changes to the half dozen other ongoing studies with Keytruda in other cancers, all of which have recently begun enrollment. But the complete lack of benefit seen in melanoma doesn't bode well for a more positive result elsewhere.
The trial results are also a setback for efforts to find effective immunotherapy partners for PD-1/L1 inhibitors. Keytruda, Bristol-Myers' Opdivo (nivolumab) and other PD-1/L1 inhibitors work quite well in some patients. But for reasons not fully understood, many patients don't see any benefit — spurring drugmakers to test new combinations in hopes of expanding the number who do.
Merck and Roche AG have had success pairing their respective checkpoint inhibitors with chemotherapy in lung cancer. And Bristol-Myers has won U.S. approval of Opdivo together with its anti-CTLA4 drug Yervoy (ipilimumab) in melanoma. Drugmakers, though, are still searching for more potent and less toxic combinations.
A count by researchers at the Cancer Research Institute last year found some 1,100 clinical studies testing cancer immunotherapies with a dizzying array of other drug types. IDO inhibitors like Incyte's epacadostat are just one corner of that research landscape.
For Incyte, ECHO-301's failure weighs heavily on the company's pipeline prospects. Shares in the biotech dropped by more than 20% Friday, shaving billions of dollars off of the company's market capitalization.
On Friday's call, company CEO Herve Hoppenot expressed confidence in the strength of Incyte's business, pointing to growth from Jakafi (ruxolitinib) as well as an upcoming decision on approval of the rheumatoid arthritis treatment barictinib.
But investors who had hoped epacadostat could prove the combination partner of choice in immuno-oncology will likely see less future potential from Incyte now.
And the ripple effects of the clinical miss are being felt elsewhere. NewLink Genetics Corp., a rival company developing a similar type of drug, announced hours after Incyte's disclosure it would review its clinical programs in light of the ECHO-301 results. While Newlink's treatment works a slightly different way, the company acknowledged the data was disappointing for the entire IDO field.
Shares in NewLink slumped by nearly 43% Friday.
Editor's note: This article has been updated to include reference to NewLink Genetics' announcement.