It was a rough start to the year for Incyte ($INCY) when its JAK inhibition drug for solid tumors flopped in February, forcing the biotech to pull the plug on a slate of trials--which saw its shares nosedive.
But, shrugging off that disappointment, the biotech has picked itself back up and is getting in on one of the hottest tickets in oncology R&D right now--PD-1/PD-L1 checkpoint inhibitors--as it announces the start of its Phase III combo deal with Merck ($MRK).
The trial will see Incyte’s experimental oral IDO1 inhibitor be used alongside Merck’s marketed PD-1 Keytruda (pembrolizumab), as a first-line treatment for patients with advanced or metastatic melanoma. The study will now start after being announced back in December; data from the ECHO-301 study is set to be posted in 2018.
Keytruda gained FDA approval two years ago as a second-line treatment for patients with melanoma, the deadliest form of skin cancer, whose cancer has spread. Late last year, its label was updated so it could be used for the initial treatment of advanced melanoma patients.
“We are very pleased to treat the first patient in the ECHO-301 study and advance the Phase 3 program evaluating epacadostat in combination with pembrolizumab,” said Steven Stein, Incyte’s CMO, in a release. “This trial--the first to test this combination in a pivotal study--is part of the larger ECHO program evaluating epacadostat, including combination studies with anti-PD-1 and PD-L1 therapies across multiple tumor types.”
More and more Big Pharmas are looking to combine their new checkpoint inhibitors with other classes of cancer drugs in an effort to further boost survival rates.
Pfizer ($PFE), Merck, Roche ($RHHBY), AstraZeneca ($AZN), and Bristol-Myers Squibb ($BMY) are all combining with other companies and their experimental/marketed meds to see if they can boost the efficacy of their checkpoint inhibitors, with a slate of deals signed this year alone.
Merck was the first to market this new form of PD-1 checkpoint inhibitors, but it has fallen far behind fierce rival BMS in the sales stakes as its PD-1 offering Opdivo, despite being approved second, has stolen a march on Keytruda and now dominates market share.
Things also got a little tougher for Merck when Opdivo won a green light from the FDA at the start of the year for solo use in previously untreated patients, regardless of their BRAF status--putting it on par with Keytruda’s license.
The Merck-Incyte Phase III trial is a randomized, double-blind, placebo-controlled study that will enroll 600 patients who will be stratified by PD-L1 expression and BRAF mutation status.
The two primary endpoints of the study are progression-free survival and overall survival, with key secondary endpoints including objective response rate, safety and tolerability.
Epacadostat is a first-in-class, selective oral inhibitor of the IDO1 enzyme that reverses tumor-associated immune suppression and restores effective antitumor immune responses.
In single-arm studies, the combination of epacadostat and immune checkpoint inhibitors has shown proof-of-concept in patients with unresectable or metastatic melanoma, according to Incyte.
In these studies, the biotech said epacadostat, combined with BMS’s melanoma CTLA-4 inhibitor Yervoy (ipilimumab), or Keytruda, improved response rates compared with studies of the immune checkpoint inhibitors alone. Ongoing Phase I and Phase II studies are investigating epacadostat in combination with PD-1 and PD-L1 inhibitors in a variety of other cancers.
Incyte will hope these trials will go well. Earlier this year Incyte stopped a range of studies for Jakafi as well as the experimental INCB39110, another JAK1. Already halted on one colon cancer trial failure, Incyte also ended the Phase III pancreatic cancer study, a separate midstage trial in colorectal cancer, a Phase II for breast and lung cancers and a dose-ranging trial for INCB39110 in pancreatic cancer.
The company, which markets Jakafi for polycythemia vera and certain forms of myelofibrosis in the U.S.--Novartis ($NVS) owns ex-U.S. rights to the drug--also got another boost today as the FDA granted a "breakthrough" designation this morning for Jakafi in patients with acute graft-versus-host disease--a condition with no currently approved treatments.
The biotech’s shares were up by 2.4% in afterhours trading yesterday, just after the Merck deal was released, after closing normal hours trading just over 1% up.
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