On September 22, 2021, the Food and Drug Administration approved ruxolitinib (Jakafi, Incyte Corp.) for chronic graft-versus-host disease (cGVHD) after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.
Efficacy was evaluated in REACH-3 (NCT03112603), a randomized, open-label, multicenter clinical trial of ruxolitinib compared to best available therapy (BAT) for corticosteroid-refractory cGVHD after allogeneic stem cell transplantation. The trial randomized 329 patients (1:1) to receive either ruxolitinib 10 mg twice daily or BAT.
The major efficacy outcome used to support approval was overall response rate (ORR) (2014 NIH Response Criteria) through cycle 7 day 1. The ORR was 70% (95% CI 63%, 77%) for the ruxolitinib arm and 57% (95% CI 49%, 65%) for the BAT arm with a difference in response rate of 13% (95% CI 3%, 23%). The median durations of response, calculated from first response to 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 BAT arms, respectively. The median times from first response to death or new systemic therapies for cGVHD were 25 months (95% CI 16.8, NE) and 5.6 months (95% CI 4.1, 7.8) for the ruxolitinib and BAT arms, respectively.
In cGVHD, the most common (incidence > 35%) hematologic adverse reactions of ruxolitinib were anemia and thrombocytopenia. The most common (incidence ≥ 20%) nonhematologic adverse reactions were infections and viral infection.
The recommended ruxolitinib starting dose for cGVHD is 10 mg given orally twice daily.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis 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 (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada, Switzerland’s Swissmedic and the United Kingdom’s Medicines & Healthcare products Regulatory Agency (MHRA). The application reviews are ongoing at the other regulatory agencies.
This application was granted priority review and orphan product designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
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