Incyte announces positive phase III REACH3 study data published in NEJM for ruxolitinib in chronic graft-versus-host disease

Incyte announced that positive data from the Phase III REACH3 study have been published in The New England Journal of Medicine (NEJM) demonstrating that treatment with ruxolitinib (Jakafi) resulted in significantly improved outcomes in patients with steroid-refractory or steroid-dependent chronic graft-versus-host disease (GVHD) compared to best available therapy (BAT). The study’s main findings, 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 ruxolitinib across all major subgroups, including baseline individual organ involvement1. REACH3 is jointly sponsored by Incyte and Novartis.

The study found that treatment with ruxolitinib led to significant improvements in ORR at Week 24 (49.7% vs. 25.6%; odds ratio [OR], 2.99; P<0.001i), the primary endpoint of the study. Also, best overall response (BOR) rate at any time up to Week 24 was achieved in 76.4% of patients in the ruxolitinib arm compared to 60.4% of patients in the BAT arm (OR, 2.17; 95% CI, 1.34-3.52). Ruxolitinib also demonstrated statistically significant and clinically meaningful improvements in key secondary endpoints: i. Patients on ruxolitinib 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<0.0001). ii. Patients treated with ruxolitinib also had greater improvements in self-reported symptoms compared to BAT1 (modified Lee Symptom Scale [mLSS] responder rate: 24.2% vs. 11.0%; OR, 2.62; P=0.001).

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

No new safety signals were observed in REACH3, and adverse events (AEs) attributable to treatment were consistent with the known safety profile of ruxolitinib. The most common AEs of grade 3 or higher in the ruxolitinib vs. BAT arms were thrombocytopenia (15.2% vs. 10.1%), anemi8%) and pneumonia (8.5% vs. 9.5%). While 37.6% and 16.5% of patients required ruxolitinib and BAT dose modifications due to AEs, respectively, the percentage of patients who discontinued treatment due to AEs was 16.4% in the ruxolitinib arm vs. 7% in the BAT arm. Mortality rates were similar across treatment arms (18.8% in the ruxolitinib arm vs. 16.5% in the BAT arm). Deaths reported as primarily due to chronic GVHD complications and/or its treatment were higher in the ruxolitinib vs. BAT arms (13.3% vs. 7.9%, respectively).

The REACH3 data serve as the basis for the Company’s supplemental New Drug Application (sNDA) for ruxolitinib for the treatment of steroid-refractory chronic GVHD in adult and pediatric patients 12 years and older, which was accepted for review by the FDA and has a Prescription Drug User Fee Act (PDUFA) target action date of September 22, 2021.

In 2019, Jakafi (ruxolitinib) was approved by the FDA for the treatment of steroid-refractory acute GVHD in adult and pediatric patients 12 years and older, based on the positive results of the Phase II REACH1 trial. Jakafi is marketed by Incyte in the U.S.; ruxolitinib (Jakavi) is licensed to Novartis ex-U.S. Outside of the U.S., Novartis regulatory submissions for acute and chronic GVHD are underway..

See- “Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease”: Robert Zeiser, M.D., Nicola Polverelli, M.D., Ph.D., Ron Ram, M.D., Shahrukh K. Hashmi, M.D., M.P.H., et al. for the REACH3 Investigators-July 15, 2021 N Engl J Med 2021; 385:228-238 . DOI: 10.1056/NEJMoa2033122.