On July 16, the U.S. Food and Drug Administration (FDA) approved belumosudil (Rezurock), a kinase inhibitor, for adult and pediatric patients aged 12 years and older with chronic graft-vs-host disease after failure of at least two prior lines of systemic therapy.
Efficacy was evaluated in KD025-213 (ClinicalTrials.gov identifier: NCT03640481), a randomized, open-label, multicenter dose-ranging trial that included 65 patients with chronic graft-vs-host disease who were treated with once-daily oral belumosudil at 200 mg.
The main efficacy outcome measure was overall response rate through cycle 7 day 1, where overall response included complete response or partial response according to the 2014 criteria of the National Institutes of Health Consensus Development Project on Clinical Trials in Chronic Graft-vs-Host Disease.
The overall response rate was 75% (95% confidence interval [CI] = 63%–85%); 6% of patients achieved a complete response and 69% achieved a partial response. 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 disease progression, death, or new systemic therapies for chronic graft-vs-host disease—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.
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, the FDA collaborated with Australia’s Therapeutic Goods Administration, Health Canada, Switzerland’s Swissmedic, and the United Kingdom’s Medicines and Healthcare products Regulatory Agency.
This review used the Real-Time Oncology Review (RTOR) 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 the FDA’s assessment. The FDA approved this application 6 weeks ahead of the FDA goal date.
This application was also granted Priority Review and Breakthrough Therapy designation.