Jul 14, 2021: 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).
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 involvement.
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 endpoint.
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).
Jakavi also demonstrated statistically significant and clinically meaningful improvements in key secondary endpoints:
- 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 BAT1 (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 Jakavi.
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).
Mortality rates were similar across treatment arms (18.8% Jakavi vs. 16.5% BAT).
Deaths reported as primarily due to chronic GvHD were slightly higher for Jakavi.
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 trial.
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.
The NEJM publication of the REACH3 results is available online at www.NEJM.org.
About Jakavi® (ruxolitinib)
Jakavi® (ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases. Jakavi is approved by the European Commission for the treatment of adult patients with polycythemia vera (PV) who are refractory to or intolerant of hydroxyurea and for the treatment of disease- related splenomegaly or symptoms in adult patients with primary myelofibrosis (MF) (also known as chronic idiopathic MF), post-polycythemia vera MF or post-essential thrombocythemia MF.
Jakavi is approved in over 100 countries for patients with MF, including EU countries, Switzerland, Canada, Japan and in more than 85 countries for patients with PV, including EU countries, Switzerland, Japan and Canada.
The exact indication for Jakavi varies by country. Additional worldwide regulatory filings are underway in MF and PV.
Novartis licensed ruxolitinib from Incyte Corporation for development and commercialization outside the United States.
Ruxolitinib is marketed in the United States by Incyte Corporation as Jakafi® for patients with PV who have had an inadequate response to or are intolerant of hydroxyurea, for patients with intermediate or high-risk MF, and steroid-refractory acute GvHD in adult and pediatric patients 12 years and older.
The recommended starting dose of Jakavi in PV is 10 mg given orally twice daily.
The recommended starting dose of Jakavi in MF is 15 mg given orally twice daily for patients with a platelet count between 100,000 cubic millimeters (mm) and 200,000 mm, and 20 mg twice daily for patients with a platelet count of >200,000 mm.
Doses may be titrated based on safety and efficacy.
There is limited information to recommend a starting dose for MF and PV patients with platelet counts between 50,000/mm and <100,000/mm.
-The maximum recommended starting dose in these patients is 5 mg twice daily, and patients should be titrated cautiously.
Jakavi is a registered trademark of Novartis AG in countries outside the United States. Jakafi is a registered trademark of Incyte Corporation.
The safety and efficacy profile of Jakavi has not yet been established outside of its approved indications.”
