FDA Approves Ruxolitinib in Chronic Graft-Versus-Host Disease

The FDA has approved ruxolitinib for the treatment of chronic graft-versus-host disease after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.

The FDA has approved ruxolitinib (Jakafi) for the treatment of patients 12 years and older with chronic graft-versus-host disease (GvHD) after failure of 1 or 2 lines of systemic therapy, according to a press release by Incyte. 

The approval is based on data from the REACH3 trial (NCT03112603), which enrollment of 330 participants.. The primary end point of REACH3 is the efficacy of ruxolitinib versus investigator’s choice of best available therapy (BAT). Secondary end points include rate of failure-free survival (FFS), best overall response, overall response rate (ORR) at the end of cycle 3, duration of response, overall survival, and others.  

“Nearly half of the people who develop chronic GVHD do not respond adequately to steroids – the current standard of care – making this life-threatening condition particularly challenging to treat,” Dr. Robert Zeiser, MD University Medical Center Freiburg, Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg, Germany, the principal investigator of the REACH3 trial in a press release. “In this clinical trial, treatment with Jakafi demonstrated significantly improved outcomes across a range of efficacy measures compared to best available therapy. This approval represents a significant advancement in the treatment of appropriate patients with chronic GVHD – for both the patients who face a poor prognosis and the healthcare providers who struggle to effectively treat them.”

REACH3 was split into 2 arms. In arm one, patients were randomized to receive ruxolitinib. In arm 2, patients received BAT with the option to crossover to ruxolitinib after cycle 6. 

At 24 weeks, the ORR for the ruxolitinib arm was 49.7% compared to the 25.6% in the BAT arm (odds ratio [OR], 2.99; 95% CI, 0.86-4.80; P < .0001). Additionally, the FFS for the experimental cohort was not reached while it stands at 5.7 months for the BAT cohort. The median duration of response was also not reached in the ruxolitinib arm compared with 6.24 months in the BAT arm. Using the modified Lee Symptom Scale, 24.2% of patients in the ruxolitinib arm reached a clinically meaningful decrease in symptoms compared with 11% in the BAT arm (OR, 2.62; 95% CI, 1.42-4.82; P = .0011). 

Ruxolitinib had a similar safety analysis compared to BAT. The rate of any-grade adverse events (AEs) was 97.6% in the ruxolitinib arm and 91.8% in the BAT arm. Grade 3 AEs were slightly more common in the BAT arm at 57.6% compared to 57% in the ruxolitinib arm. Similarly, serious AEs occurred in 36.7% of patients in the BAT arm compared to 33.3% of patients in the ruxolitinib arm. The death rate in the BAT arm was 16.5% compared to 18.8% in the ruxolitinib arm. Any grade anemia was seen in 29.1% of patients in the ruxolitinib arm and 12.7% in the BAT arm. Grade 3 or higher anemia was seen in 12.7% of patients in the ruxolitinib arm and 7.6% of patients in the BAT arm. Any grade thrombocytopenia occurred in 21.2% of patients in the ruxolitinib arm and 14.6% of patients in the BAT arm. Grade 3 or higher thrombocytopenia occurred in 15.2% of patients in the ruxolitinib arm compared to 10.1% of patients in the BAT arm. 

The approval comes after the approval decision was pushed back 3 months in order to accommodate additional REACH3 data. 

“GVHD is the leading cause of morbidity and mortality in patients following an allogeneic stem cell transplant, yet there historically have been limited treatment options available beyond first-line systemic therapies,” stated Steven Stein, MD, chief medical officer, Incyte in a press release. “Incyte is proud to have contributed to the overall scientific understanding of GVHD through our REACH program, which has led to important treatment advances on behalf of patients and the medical community, including today’s approval of Jakafi for certain people who develop chronic GVHD.”

REFERENCE:
Incyte announces FDA approval of Jakafi® (ruxolitinib) for treatment of chronic graft-versus-host disease (GVHD). News release. Incyte. September 22, 2021. Accessed September 22, 2021. https://bit.ly/3lN6lPo.