On July 16, 2021, the U.S. Food and Drug Administration (FDA) approved belumosudil (RezurockTM), a kinase inhibitor, for the treatment of chronic graft-versus-host disease (chronic GVHD) in adult and pediatric patients 12 years and older after failure of at least two prior lines of systemic therapy.
Efficacy was evaluated in a randomized, open-label, multicenter, dose-ranging trial (KD025-213, NCT03640481) that included 65 patients with chronic GVHD who were treated with belumosudil 200 mg orally once daily.
The main efficacy outcome measure was overall response rate (ORR) through cycle seven, day one, where overall response included complete response (CR) or partial response (PR) according to the 2014 criteria of the National Institutes of Health consensus development project on clinical trials in chronic GVHD. The ORR was 75% (95% CI = 63, 85); 6% of patients achieved a CR, and 69% achieved a PR. The median time to first response was 1.8 months (95% CI = 1.0, 1.9). The median duration of response, calculated from first response to progression, death, or new systemic therapies for chronic GVHD, was 1.9 months (95% CI = 1.2, 2.9). In patients who achieved response, no death or new systemic therapy initiation occurred in 62% (95% CI = 46, 74) of patients for at least 12 months since response.
The most common adverse reactions (≥ 20%), including laboratory abnormalities, were infections, asthenia, nausea, diarrhea, dyspnea, cough, edema, hemorrhage, abdominal pain, musculoskeletal pain, headache, decreased phosphate, increased gamma glutamyl transferase, decreased lymphocytes, and hypertension.
The recommended dosage of belumosudil is 200 mg taken orally once daily with food.
The review was conducted under Project Orbis, an initiative of FDA’s Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For the review, FDA collaborated with Australia’s Therapeutic Goods Administration, Health Canada, Switzerland’s Swissmedic, and the United Kingdom’s Medicines and Healthcare products Regulatory Agency.
The review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved the application six weeks ahead of its goal date.
The application was granted priority review and breakthrough therapy 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 800-FDA-1088.
For assistance with single-patient investigational new drug applications for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.