Incyte's Graft-Versus-Host Trial Fails to Meet Primary Endpoint

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Incyte Corporation’s pivotal Phase III GRAVITAS-301 trial of itacitinib in combination with corticosteroids in treatment-naïve acute graft-versus-host disease (GVHD) didn’t hit the primary endpoint. Company shares dropped almost 10% at the news.

The primary endpoint was improved overall response rate (ORR) at Day 28 compared to placebo plus corticosteroids. The ORR was 74% compared to 66.4%, respectively. Although there was improvement, it did not achieve statistical significance.

There was also no difference seen in non-relapse mortality (NRM) at Month 6, which was the trial’s key secondary endpoint.

Itacitinib is a novel and selective JAK1 inhibitor. It is being evaluated as first-line treatment for both acute and chronic GVHD. GRAVITAS-301 is a randomized, double-blind, placebo-controlled pivotal Phase III trial.

GVHD is a disease where donated bone marrow or stem cells treat the recipient’s body as alien, and the donated cells or marrow attack the body. Some researchers believe that chronic GVHD is a later phase of acute GVHD, although others speculate that it is a separate disease similar to an autoimmune disorder.

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“The result of this study is disappointing,” said Steven Stein, Incyte’s chief medical officer. “However, we remain committed to building on the success of the REACH program for ruxolitinib, which showed positive results in steroid refractory acute GVHD.”

“Additionally,” Stein went on, “we will continue to study the role of JAK inhibition in chronic GVHD and in the prophylactic setting, as we seek to develop treatments for patients with this debilitating and often fatal disease.”

The drug is also being evaluated in ulcerative colitis. Incyte markets another JAK inhibitor, Jakafi (ruxolitinib) for acute GVHD, as well as for polycythemia vera and myelofibrosis.

In late November 2019, the U.S. Food and Drug Administration accepted the company’s New Drug Application (NDA) under Priority Review for pernigatinib. This drug is a selective fibroblast growth factor receptor (FGFR) inhibitor. The NDA is for previously treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements.

The NDA was based on results from the FIGHT-202 study, which showed the drug as a monotherapy had an ORR of 36%, the primary endpoint, and median duration of response (DOR) of 7.5 months, the secondary endpoint, with a median follow-up of 15 months.

“There is a significant need for new therapies for patients with cholangiocarcinoma, who have limited treatment options beyond first-line chemotherapy and often face a poor prognosis,” said Peter Lanmuir, Incyte’s group vice president of Targeted Therapeutics, in a statement at the time. “We are very pleased that the FDA has accepted our NDA for Priority Review which we believe represents an important step toward providing the first treatment option for patients with previously treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements. We intend to work closely with the FDA to bring this innovative targeted therapy to patients suffering from this devastating disease as soon as possible.”

The agency gave the NDA a target action date of May 30, 2020.

Cholangiocarcinoma is a rare type of cancer of the bile duct.

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