FDA Grants Priority Review to Ruxolitinib in Steroid-Refractory cGVHD


The FDA has accepted a supplemental New Drug Application for ruxolitinib and granted it Priority Review as a potential treatment option for adult and pediatric patients 12 years and older with steroid-refractory chronic graft-versus-host disease.

The FDA has accepted a supplemental New Drug Application (sNDS) for ruxolitinib (Jakafi) and granted it Priority Review as a potential treatment option for adult and pediatric patients 12 years and older with steroid-refractory chronic graft-versus-host disease (GVHD), announced Incyte, in a press release.1

“Chronic GVHD is a life-threatening complication following stem cell transplant that burdens a vulnerable patient population, which today has limited treatment options,” said Peter Langmuir, MD, group vice president, Oncology Targeted Therapies, Incyte, in a statement.

The sNDA for ruxolitinib under this indication was supported by findings from the randomized phase 3 REACH3 study of ruxolitinib versus best available therapy (BAT) in patients with steroid-refractory chronic GVHD. Results from the study presented during the 2020 American Society of Hematology (ASH) Annual Meeting showed that the overall response rate (ORR) achieved with ruxolitinib was significantly higher than with BAT. Ruxolitinib led to a 49.7% ORR rate compared with a 25.6% ORR in the BAT arm (odds ratio [OR], 2.99; 95% CI, 0.86-4.80; P < .0001) at 24 weeks.1,2

Aside from ORR, which was the primary end point of the study, ruxolitinib showed benefit over BAT in terms of the secondary end points of failure-free survival (FFS), symptom improvement, and duration of response.

The ruxolitinib-treated patients had a median FFS that was not yet reached compared with 5.7 months for the BAT arm (HR, 0.37; 95% CI, 0.268-0.510; P < .0001). On the modified Lee Symptom Scale (mLSS), ruxolitinib led to a greater number of responses compared with BAT, with 24.2% of patients reaching a clinically meaningful decrease in symptoms compared with 11%, respectively (OR, 2.62; 95% CI, 1.42-4.82; P = .0011).

With ruxolitinib, best overall responses were higher at 76.4% when compared with the BAT arm, which had a rate of 60.4% (OR, 2.17; 95% CI, 1.34-3.52). The median duration of best overall response was not reached with ruxolitinib versus 6.24 months in the BAT arm.

The analysis of safety in the REACH3 study showed that both ruxolitinib and BAT exhibited similar adverse event (AE) rates. The rate of any-grade AEs was 97.6% with ruxolitinib versus 91.8% with BAT. Grade 3 AEs occurred in 57% of the ruxolitinib arm and 57.6% of the BAT arm. There were also serious AEs observed in the study subjects, which occurred more frequently among patients treated with BAT (36.7%) compared with those who received ruxolitinib (33.3%).

Both treatment arms showed similar death rates, which was 18.8% with ruxolitinib versus 16.5% in the BAT arm.

A number of AEs occurred in more than 10% of patients, of which the most common for patients treated with ruxolitinib was cytopenias. Also, the ruxolitinib arm experienced significant any-grade anemia (29.1%), grade 3 or higher anemia (12.7%.), any-grade thrombocytopenia (21.2%), and grade 3 or higher thrombocytopenia (15.2%). In comparison, patients in the BAT arm had a 12.7% rate of any-grade anemia, 7.6% rate of grade 3 anemia, 14.6% rate of any-grade thrombocytopenia, and a 10.1% rate of grade 3 or higher thrombocytopenia.

Viral infections were the most common type of infection in the study and were seen in 33.9% of patients in the ruxolitinib arm versus 29.1% in the BAT arm. Reports of bacterial infections were given by 27.9% of patients in the ruxolitinib arm versus 25.9% of patients in the BAT arm. Fungal infections were reported by 11.5% of the ruxolitinib arm compared with 5.7% of the BAT arm.

Based on these results, all of the primary and secondary end points for the REACH3 study were achieved.

“The acceptance of this sNDA represents an important milestone for Incyte as we continue our work towards helping more people living with GVHD, particularly for those who do not respond to steroids. We look forward to working closely with the FDA to bring this innovative therapy to patients and to providing continued support to the GVHD community in the United States,” stated Langmuir, in the press release.1

Incyte’s close work with the FDA will involve the review of the sNDA as part of the Project Orbis program, an initiative of the FDA Oncology Center of Excellence. The review will be completed within 6 months of the application being granted Priority Review, and will reviewed for potential approval in Canada, Australia, Switzerland, Brazil, and the United Kingdom as well. The Prescription Drug User Fee Act target action date has been set as June 22, 2021.


1. Incyte announces acceptance and Priority Review of sNDA for Jakafi® (ruxolitinib) as a treatment for patients with chronic graft-versus-host disease, News release. Incyte. February 22, 2021. Accessed February 23, 2021. https://bit.ly/2ZEOors

2. Zeiser R, Polverelli N, Ram R, et al. Ruxolitinib (RUX) Vs Best Available Therapy (BAT) in Patients with Steroid-Refractory/Steroid-Dependent Chronic Graft-Vs-Host Disease (cGVHD): Primary Findings from the Phase 3, Randomized REACH3 Study. Presented at: 2020 ASH Annual Meeting & Exposition; December 5-8, 2020; Virtual. Abstract 77.

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