Incyte announced that a Phase III trial of the investigational JAK1 inhibitor itacitinib in patients with treatment-naïve acute graft-versus-host disease (GVHD) failed to meet its primary endpoint. "The result of this study is disappointing," remarked chief medical officer Steven Stein, with shares in the company falling up to 12% on the news.
The GRAVITAS-301 trial randomised 439 patients with acute GVHD to receive first-line treatment with itacitinib or placebo, both in combination with corticosteroids. The study's main goal is overall response rate (ORR) at day 28, defined as the proportion of subjects demonstrating a complete response, very good partial response or partial response, while a key secondary endpoint is non-relapse mortality at month six.
Results showed that the ORR was 74% for itacitinib, versus 66.4% for placebo, while Incyte noted that there was no difference observed in non-relapse mortality at month six between the two groups. The drugmaker indicated that data from the study will be submitted for presentation at an upcoming scientific meeting.
In October last year, Incyte announced  that the Phase III REACH2 study conducted by partner Novartis showed that Jakafi (ruxolitinib) significantly improved ORR at day 28 versus best available therapy in patients with steroid-refractory acute GVHD. The JAK1/JAK2 inhibitor is currently approved  in the US for the treatment of steroid-refractory acute GVHD in adult and paediatric patients 12 years and older (for related analysis, see ViewPoints: Ruxolitinib's Phase III win in GVHD nice for Novartis but Incyte has bigger fish to fry ).
Stein said that despite the failure of the GRAVITAS-301 trial, "we remain committed to building on the success of the REACH programme for [Jakafi]," adding "we will continue to study the role of JAK inhibition in chronic GVHD and in the prophylactic setting."