FDA Grants Ruxolitinib Priority Review to Treat Chronic GVHD

The FDA has granted priority review of the supplemental New Drug Application for ruxolitinib for the treatment of steroid-refractory chronic graft-versus host disease (GVHD).

The FDA has granted priority review of the supplemental New Drug Application (sNDA) for ruxolitinib (Jakafi) for the treatment of steroid-refractory chronic graft-versus host disease (GVHD) in adults and children age 12 years and older. In 2019, the drug was approved to treat steroid-refractory acute GVHD in the same population.

At the American Society of Hematology (ASH) Annual Meeting & Exposition, held in December 2020, Incyte had released the results of the REACH3 trial,1 which are being used as part of the sNDA submission. The trial was a randomized study comparing ruxolitinib with the best available therapy (BAT) in patients with steroid-refractory chronic GVHD.

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

In the trial presented at ASH, 329 patients were randomized to receive either ruxolitinib (n = 165) or BAT (n = 164). In the overall trial, 48% of patients had moderate chronic GVHD and 52% had severe chronic GVHD. As of May 8, 2020, 50% of the patients had discontinued ruxolitinib compared with 74% who discontinued BAT; in addition, 61 patients (37%) had crossed over from the BAT arm to the ruxolitinib arm. Patients taking BAT were allowed to crossover to the ruxolitinib arm on or after cycle 7 day 1 (C7D1) if they did not achieve or maintain complete response or partial response, developed toxicity to BAT or had a chronic GVHD flare.

According to the researchers, ruxolitinib demonstrated a superior efficacy. Failure-free survival (FFS) was significantly longer for patients treated with ruxolitinib: the median FFS was not reached for the ruxolitinib arm compared with 5.7 months for the BAT arm (HR, 0.370 [95% CI, 0.268-0.510]; P < .0001).

Ruxolitinib also had a superior overall response rate (ORR) at week 24, the primary end point of the trial. The ORR for patients taking ruxolitinib was 50% vs 26% for the BAT arm (odds ratio, 2.99; P < .0001).

“Based on the compelling REACH3 results, we now have a potential new standard of care for these patients,” presenting author Robert Zeiser, MD, of the University Hospital Freiburg, in Freiburg, Germany, said in a statement at the time the paper was presented at ASH.

The target Prescription Drug User Fee Act action date for Jakafi is June 22, 2021.

Reference

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 the 62nd American Society of Hematology Annual Meeting and Exposition, Virtual; December 5-8, 2020; Abstract 77.