Results of the Phase III REACH2 study show that Novartis' Jakavi (ruxolitinib) improves outcomes across a range of efficacy measures in patients with steroid-refractory acute graft-versus-host disease (GvHD) compared to best available therapy (BAT).
In the study, patients treated with Jakavi experienced significantly greater overall response rate (ORR) compared to BAT (62% vs. 39%) at Day 28, the primary endpoint of the study.
For the key secondary endpoint, those in the Jakavi group maintained significantly higher durable ORR (40% vs. 22% at eight weeks, and Novartis' drug was associated with longer median failure free survival (FFS) than BAT (5.0 months vs. 1.0 months as well as showing a positive trend with other secondary endpoints, including duration of response.
The findings are particularly pertinent as GvHD, a serious and common complication of allogeneic stem cell transplants, has a one-year death rate as high as 80% in its acute form, and REACH2 is the first Phase III study in acute GvHD to have met its primary endpoint.
"Patients with acute graft-versus-host disease face life-threatening challenges with limited treatment options, particularly for the nearly half of individuals who do not respond to initial steroid therapy," said Robert Zeiser, University Hospital Freiburg, Department of Haematology, Oncology and Stem Cell Transplantation, Freiburg, Germany.
"These new data from REACH2 showing superiority of Jakavi over current standard-of-care therapies add to a growing body of evidence on how targeting the JAK pathway can be an effective strategy in this difficult-to-treat condition."
Also of note, the first said no new safety signals were observed in REACH2, and adverse events (AEs) attributable to treatment were consistent with the known safety profile of Jakavi, the most common of which were thrombocytopaenia, anaemia and cytomegalovirus infection.
"Compelling results from REACH2, the first successful randomized Phase III trial in patients with steroid-refractory acute graft-versus-host-disease, give us confidence in the potential of Jakavi to confront this difficult condition," said John Tsai, head Global Drug Development and chief medical officer at Novartis. "We look forward to initiating discussions with ex-US regulatory authorities."
The results are published in The New England Journal of Medicine.