A late-stage clinical trial testing the combination of a Merck cancer treatment and a new type of cancer drug developed by Incyte has failed, dealing a blow to a new drug class that many hoped would expand the reach of cancer immunotherapy.
The Phase 3 study in melanoma tested the FDA-approved Merck (NYSE: MRK) cancer drug pembrolizumab (Keytruda) in combination with epacadostat, which was developed by Wilmington, DE-based Incyte (NASDAQ: INCY). The companies said Friday that an external review of the Phase 3 data concluded that compared to those treated with the Merck drug alone, the combination treatment did not hit the study’s main goal of improving progression-free survival, or the length of time that a patient lives with the disease without the cancer worsening.
The combination treatment is also expected to miss the secondary goal of improving overall survival, which is the length of time patients survive after receiving treatment. Based on those findings, Merck and Incyte said that they would stop the study.
Shares of Incyte fell 22.9 percent to $64.02 apiece Friday. Merck’s shares dipped 2.5 percent to $53.36 each at the closing bell. The fallout from the clinical failure also hit other companies. NewLink Genetics (NASDAQ: NLNK)—which has a drug similar to Incyte’s in mid-stage clinical testing—saw its stock price plummet 42.6 percent to $4.20 per share.
Merck’s pembrolizumab is a type of cancer immunotherapy called a checkpoint inhibitor. These drugs release the brakes on the body’s immune system, enabling cancer-killing T cells to do their work. But checkpoint inhibitors do not work on all cancer patients. In the hopes of bringing these treatments to more cancer patients, Merck and others have been seeking out new drugs that could be combined with their respective checkpoint inhibitors.
Incyte’s drug, like NewLink’s, is part of a new class of drugs called IDO inhibitors. These drugs block IDO, an enzyme produced by tumors that suppresses the body’s immune cells. The effect of IDO is to help tumors evade detection by the immune system. The concept of blocking IDO has drawn considerable interest to the new drug class. In 2015, Bristol-Myers Squibb (NYSE: BMY) paid $800 million up front to acquire a big piece of Flexus Biosciences, including its IDO drug. Last week, San Francisco-based Tempest Therapeutics raised $70 million in financing to back its IDO inhibitor, which executives say could have advantages over the current slate of experimental IDO drugs.
The Merck/Incyte study, called KEYNOTE-252, enrolled more than 700 patients whose melanoma cannot be removed by surgery, or whose cancer has spread. Although a number of companies have reached clinical trials testing their checkpoint inhibitors in combination with IDO inhibitors, KEYNOTE was furthest along, and the readout of its clinical data was anticipated as potentially validating the approach of targeting the enzyme. Instead, the failure of the Incyte drug has led companies to reevaluate their positions.
NewLink, which is in Phase 2 testing of its IDO drug indoximod in combination with the AstraZeneca (NYSE: AZN) checkpoint inhibitor durvalumab (Imfinzi), says its drug works in a different way than Incyte’s. Even so, NewLink called the failure of the Incyte drug “a disappointing result for the IDO field.” NewLink announced late Friday that the Ames, IA, company will review its clinical programs.
In a prepared statement, Steven Stein, Incyte’s chief medical officer, said the KEYNOTE clinical trial data will help improve the understanding of combining IDO drugs and checkpoint inhibitors. Merck and Incyte plan to analyze the data and submit them for presentation at a future, unspecified scientific meeting.
Metastatic melanoma cells image by the National Cancer Institute.