On September 22, the U.S. Food and Drug Administration approved ruxolitinib (Jakafi), a JAK inhibitor, for the treatment of chronic graft-vs-host disease (GVHD) after failure of one or two lines of systemic therapy in adult and pediatric patients aged 12 years and older.
Efficacy was evaluated in REACH3 (ClinicalTrials.gov identifier NCT03112603), a randomized, open-label, multicenter clinical trial of ruxolitinib compared to best available therapy for corticosteroid-refractory chronic GVHD after allogeneic stem cell transplantation. The trial randomly assigned 329 patients (1:1) to receive either ruxolitinib at 10 mg twice daily or best available therapy.
The major efficacy outcome used to support approval was overall response rate (2014 NIH Response Criteria) through cycle 7, day 1. The overall response rate was 70% (95% confidence interval [CI] = 63%–77%) in the ruxolitinib arm and 57% (95% CI = 49%–65%) in the best available therapy arm, with a difference in response rate of 13% (95% CI = 3%–23%).
The median durations of response, calculated from first response to disease progression, death, or new systemic therapies for chronic GVHD, were 4.2 months (95% CI = 3.2–6.7) and 2.1 months (95% CI = 1.6–3.2) for the ruxolitinib and best available therapy arms, respectively. The median times from first response to death or new systemic therapies for chronic GVHD were 25 months (95% CI = 16.8–not evaluable) and 5.6 months (95% CI = 4.1–7.8) for the ruxolitinib and best available therapy arms, respectively.
The most common (incidence > 35%) hematologic adverse reactions associated with ruxolitinib in patient with chronic GVHD were anemia and thrombocytopenia. The most common (incidence ≥ 20%) nonhematologic adverse reactions were infections and viral infection.
The recommended ruxolitinib starting dose for chronic GVHD is 10 mg given orally twice daily.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency, Health Canada, Switzerland’s Swissmedic, and the United Kingdom’s Medicines & Healthcare products Regulatory Agency. The application reviews are ongoing at the other regulatory agencies.
This application was granted Priority Review and Orphan Drug designation.