FDA Grants Priority Review to Ruxolitinib for Chronic GVHD

February 22, 2021 - The FDA has granted priority review to a supplemental new drug application for ruxolitinib for use in adult and pediatric patients aged 12 years and older with steroid-refractory chronic graft-versus-host disease.

Peter Langmuir, MD

Peter Langmuir, MD

The FDA has granted priority review to a supplemental new drug application (sNDA) for ruxolitinib (Jakafi) for use in adult and pediatric patients aged 12 years and older with steroid-refractory chronic graft-versus-host disease (GVHD), according to an announcement from Incyte.1

The application is based on data from the phase 3 REACH3 trial (NCT033112603), which showed that ruxolitinib elicited a significantly higher overall response rate (ORR) compared with best available therapy (BAT), at 49.7% versus 25.6%, respectively, in patients with steroid-refractory chronic GVHD (odds ratio [OR], 2.99; 95% CI, 0.86-4.80; P <.0001).2

Ruxolitinib was also linked with a longer median failure-free survival (FFS) compared with BAT at week 24; the FFS had not yet been reached with the JAK2 inhibitor versus 5.7 months with BAT (HR, 0.370; 95% CI, 0.268-0.510; P <.0001).

Moreover, ruxolitinib resulted in improved symptom burden, defined by the modified Lee Symptom Scale (mLSS), compared with BAT. Specifically, 24.2% of those in the investigational arm experienced a clinically meaningful decrease in symptoms versus 11% of those in the control arm (OR, 2.62; 95% CI, 1.42-4.82; P = .0011).

Under the Prescription Drug User Fee Act, the FDA must make a decision by June 22, 2021.

“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 of Oncology Targeted Therapies at Incyte, said in a press release. “The acceptance of this sNDA represents an important milestone for Incyte as we continue our work toward helping more people living with GVHD, particularly for those who do not respond to steroids.”

In the trial, a total of 329 patients were randomized to receive ruxolitinib at 10 mg, twice daily (n = 165) with or without steroids and a calcineurin inhibitor or BAT (n = 164). Investigators selected BAT prior to randomization and they chose from a list of 10 options, which included extracorporeal photopheresis, ibrutinib (Imbruvica), methotrexate, and others.

Notably, participants who had been randomized to BAT and who experienced an inadequate response to treatment, a flare, or who were unable to tolerate the treatment, were permitted to crossover to the ruxolitinib arm following week 24.

The primary end point of the trial was ORR, which was evaluated at week 24, while the secondary end points included FFS and symptom burden.

The patient characteristics at baseline were found to be well balanced between the 2 treatment arms. Participants had similar ages, sex, and chronic GVHD severity across the arms. More than half of participants in each cohort had severe disease.

Approximately 50% of patients in the investigational arm were still receiving treatment with ruxolitinib at the time of the primary analysis at week 24 and 49.7% had stopped treatment. In the ruxolitinib arm, the most common reasons for discontinuation included toxicity and lack of efficacy. In the BAT arm, 25.6% were still receiving treatment and 74.4% had discontinued treatment because of lack of efficacy.

Moreover, 37.2% of patients who were randomized to the control arm ended up crossing over to the experimental arm.

Of those who experienced a response on the ruxolitinib arm, 43% had a partial response (PR) and 6.7% had a complete response (CR). Of those who achieved a response on the BAT arm, 22.6% experienced a PR, while 3% had a CR. Best overall response proved to be higher in the ruxolitinib arm versus the BAT arm, at 76.4% compared with 60.4%, respectively (OR, 2.17; 95% CI, 1.34-3.52). Additionally, the median duration of best overall response had not yet been reached in the investigational arm versus 6.24 months in the control arm.

Regarding safety, patients who received ruxolitinib experienced a slightly higher rate of all-grade adverse effects compared with those who received chemotherapy, at 97.6% versus 91.8%, respectively. However, rates of grade 3 or higher toxicities were reported in 57.0% of those on the investigative arm versus 57.6% of those on the control arm.

Serious toxicities occurred in 36.7% of those in the BAT arm versus 33.3% of those on the ruxolitinib arm. Rates of death up to the data cutoff proved to be comparable between the arms. Risk of death was 18.8% and 16.5% in the ruxolitinib and BAT arms, respectively.

Cytopenias were the most frequently reported toxicity in those who received ruxolitinib. Moreover, 29.1% of those in the investigative arm experienced any-grade anemia, while 12.7% had grade 3 or higher anemia; these rates in the BAT arm were 12.7% and 7.6%, respectively. Moreover, 21.2% of patients who received ruxolitinib had any-grade thrombocytopenia, while 15.2% had cases that were grade 3 or higher in severity; these rates were 14.6% and 10.1%, respectively.

In May 2019, the FDA approved ruxolitinib for the treatment of adult and pediatric patients aged 12 years or older with steroid-refractory acute GVHD, based on data from the phase 2 REACH1 trial (NCT029533678). Results showed that ruxolitinib, when paired with corticosteroids, resulted in an ORR of 57% at day 28 in this population, with a 31% CR rate.3


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 22, 2021. http://bwnews.pr/3pFaDs1.

2. Lee S. Ruxolitinib vs best available therapy in patients with glucocorticoid-refractory chronic graft-vs-host disease: primary findings from the phase 3, randomized REACH3 study. Presented at: 2021 Transplantation and Cellular Therapy Meetings; February 8-12, 2021; virtual. Abstract 82.

3. FDA approves Jakafi (ruxolitinib) for the treatment of patients with acute graft-versus-host disease. News release. Incyte. May 24, 2019. Accessed February 22, 2021. https://bit.ly/2ZES0tx

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