Benzinga | Jul 14, 2021 05:01PM EDT

Incyte Announces Highlights Publication Of Phase 3 REACH3 Study Data Published in NEJM for Ruxolitinib (Jakafi) in Chronic Graft-Versus-Host Disease

* Phase 3 REACH3 data show that ruxolitinib (Jakafi(r)) significantly improved overall response rate (ORR) at Week 24 (49.7% vs. 25.6%) with a higher best overall response rate (76.4% vs. 60.4%) vs. best available therapy among patients with steroid-refractory/dependent chronic graft-versus-host disease (GVHD) 1

* Additional new subgroup analysis demonstrated higher ORR for patients treated with ruxolitinib regardless of the individual organs involved at baseline1

* Chronic GVHD is a life-threatening complication of stem cell transplants and half of patients become refractory to or dependent on first-line steroids2,3

* REACH3 data serve as the basis for the supplemental New Drug Application (sNDA) undergoing review with the U.S. Food and Drug Administration (FDA)

Incyte (NASDAQ:INCY) today announced that positive data from the Phase 3 REACH3 study have been published in The New England Journal of Medicine (NEJM) demonstrating that treatment with ruxolitinib (Jakafi(r)) 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)1. 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.

"Results from the REACH3 study published in NEJM are extremely compelling and underscore the potential benefits ruxolitinib can offer appropriate patients facing the serious complications associated with chronic GVHD," said Peter Langmuir, M.D., Group Vice President, Oncology Targeted Therapies, Incyte. "At Incyte, we remain committed to advancing our research and understanding of this complex disease, and will continue to work closely with the FDA to bring this innovative treatment to chronic GVHD patients, who currently have limited treatment options."

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 study1. 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)1. Ruxolitinib also demonstrated statistically significant and clinically meaningful improvements in key secondary endpoints1:

* 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).

* 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)ii.

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 baseline1.

No new safety signals were observed in REACH3, and adverse events (AEs) attributable to treatment were consistent with the known safety profile of ruxolitinib1. The most common AEs of grade 3 or higher in the ruxolitinib 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 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 arm1. Mortality rates were similar across treatment arms (18.8% in the ruxolitinib arm vs. 16.5% in the BAT arm)1. 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)1.

"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 ruxolitinib for patients with chronic GVHD who have not adequately responded to first-line steroids."

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 U.S. Food and Drug Administration (FDA) and has a Prescription Drug User Fee Act (PDUFA) target action date of September 22, 2021.

GVHD is a condition that can occur after an allogeneic stem cell transplant (the transfer of stem cells from a donor) where the donated cells initiate an immune response and attack the transplant recipient's organs, leading to significant morbidity and mortality. There are two major forms of GVHD: acute, which generally occurs within 100 days of transplant, and chronic, which generally occurs more than 100 days after transplant2. GVHD can affect multiple organ systems including the skin, gastrointestinal (digestive) tract and liver.

In 2019, Jakafi(r) (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 2 REACH1 trial4. Jakafi is marketed by Incyte in the U.S.; ruxolitinib (Jakavi(r)) is licensed to Novartis ex-U.S. Outside of the U.S., Novartis regulatory submissions for acute and chronic GVHD are underway.

The NEJM publication of the REACH3 results is available online.