Novartis announces NEJM publication of positive Phase III REACH3 data for Jakavi in chronic GvHD

Novartis announced that The New England Journal of Medicine (NEJM) published positive results from the Phase III REACH3 trial demonstrating Jakavi® (ruxolitinib) significantly improved outcomes in patients with steroid-refractory/dependent chronic graft-versus-host disease (GvHD) compared to best available therapy (BAT)1. The study’s main findings, which had been previously presented at the 62nd American Society of Hematology (ASH) Annual Meeting, were published along with new subgroup analyses showing favorable overall response rate (ORR) at week 24 for Jakavi across all major subgroups, including baseline individual organ involvement1. REACH3 is jointly sponsored by Novartis and Incyte.

“Patients with chronic GvHD can experience severe and life-threatening symptoms in different organs around the body, which makes the disease more difficult to treat and increases the risk of poor outcomes,” said Dr. Robert Zeiser, University Hospital Freiburg, Department of Haematology, Oncology and Stem Cell Transplantation, Freiburg, Germany. “With these new results from REACH3, we can see more clearly the potential benefits of what may become a new standard of care for chronic GvHD patients who have not adequately responded to first-line steroids.”

The study found that treatment with Jakavi led to significant improvements in ORR at week 24 (49.7% vs. 25.6%; odds ratio [OR], 2.99; P<0.001i), which was the trial’s primary endpoint1. Also, best overall response (BOR) rate at any time up to week 24 was achieved in 76.4% of patients in the Jakavi arm compared to 60.4% in the BAT arm (OR, 2.17; 95% CI, 1.34-3.52)1. Jakavi also demonstrated statistically significant and clinically meaningful improvements in key secondary endpoints1:

  • Patients on Jakavi achieved longer failure-free survival (FFS) than patients receiving BAT (median FFS not yet reached vs. 5.7 months; hazard ratio, 0.37; 95% CI, 0.27 to 0.51; P<0.001).
  • Jakavi-treated patients also had greater improvements in self-reported symptoms compared to BAT(24.2% vs. 11.0%; OR, 2.62; P=0.001)ii.

In addition, a new subgroup analysis included in the publication found that patients on Jakavi had better outcomes regardless of the individual organs affected at baseline1.

“These new Jakavi data underscore its potential benefits and the importance of making it available to patients at risk for an all-too-common and life-threatening complication of stem cell transplants,” said Susanne Schaffert, PhD, President, Novartis Oncology. “We are pleased that regulatory submissions are underway and will continue to work toward wide accessibility of this important new medicine for GvHD.”

No new safety signals were observed in REACH3, and adverse events (AEs) attributable to treatment were consistent with the mechanism of action and the known safety profile of Jakavi1. The most common AEs of grade 3 or higher in the Jakavi vs. BAT arms were thrombocytopenia (15.2% vs. 10.1%), anemia (12.7% vs. 7.6%), neutropenia (8.5% vs. 3.8%) and pneumonia (8.5% vs. 9.5%). While 37.6% and 16.5% of patients required Jakavi and BAT dose modifications due to AEs, respectively, the number of patients who discontinued treatment due to AEs was low (16.4% Jakavi vs. 7% BAT)1. Mortality rates were similar across treatment arms (18.8% Jakavi vs. 16.5% BAT)1. Deaths reported as primarily due to chronic GvHD were slightly higher for Jakavi1.

In 2019, the US Food and Drug Administration (FDA) approved ruxolitinib (marketed by Incyte Corporation in the US 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 trial6. The Incyte filing in the US for Jakafi in steroid-refractory chronic GvHD is currently undergoing review by the FDA. Outside the US, Novartis regulatory submissions for acute and chronic GvHD are underway worldwide.

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