Data from the Phase III REACH2 study published today in The New England Journal of Medicine show 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). The results of REACH2, the first Phase III study in acute GvHD to have met its primary endpoint, reinforce findings of the previously reported Phase II REACH1 study. The new data was also selected for presentation at the Presidential Symposium of the European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting, to be held 30 August to 2 September in Madrid.
In REACH2, patients treated with Jakavi experienced significantly greater overall response rate (ORR) vs. BAT (62% vs. 39%; p<0.001) at Day 28, the primary endpoint of the study. For the key secondary endpoint, patients treated with Jakavi maintained significantly higher durable ORR (40% vs. 22%; p<0.001) at eight weeks. Additionally, Jakavi was associated with longer median failure free survival (FFS) than BAT (5.0 months vs. 1.0 months; hazard ratio 0.46, 95% CI, 0.35 to 0.60), and showed a positive trend with other secondary endpoints, including duration of response.
“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.”
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 AEs were thrombocytopenia, anemia and cytomegalovirus infection. While 38% and 9% of patients required Jakavi and BAT dose modifications, respectively, the number of patients who discontinued treatment due to AEs was low (11% and 5%, respectively).
“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, Novartis. “We look forward to initiating discussions with ex-US regulatory authorities.”
In 2019, the US Food and Drug Administration approved ruxolitinib (marketed by Incyte Corporation in the U.S. as Jakafi) for the treatment of steroid-refractory acute GvHD in adult and pediatric patients 12 years and older based on results of the single arm Phase II REACH1 trial. The Phase III REACH3 study in patients with steroid-refractory chronic GvHD is ongoing and results are expected in the second half of this year.