On July 16, 2021, belumosudil, an inhibitor of Rho-associated coiled-coil kinase 2, was approved for the treatment of adult and pediatric patients 12 years and older with chronic graft-vs-host disease after the failure of at least two prior lines of systemic therapy.1
Supporting Efficacy Data
Approval was based on findings from the KD025-213 trial (ClinicalTrials.gov identifier NCT03640481), in which 65 patients received oral belumosudil at 200 mg once daily. The main efficacy outcome measure was overall response rate through cycle 7, day 1, according to the 2014 National Institutes of Health consensus criteria.
The overall response rate was 75% (95% confidence interval [CI] = 63%–85%), with a complete response in 6%. The median time to first response was 1.8 months (95% CI = 1.0–1.9 months). Among responders, no deaths or new systemic therapy initiation occurred in 62% of patients for at least 12 months since response.
How It Is Used
The recommended dose of belumosudil is 200 mg orally once daily until progression of chronic graft-vs-host disease that requires new systemic therapy. Product labeling provides instructions on dose modifications for adverse reactions, including hepatotoxicity and grade 3 and 4 toxicity, as well as instructions on belumosudil dose increases when used concomitantly with strong CYP3A inducers (eg, phenobarbital, rifampicin) or proton pump inhibitors.
Among 83 adults with chronic graft-vs-host disease receiving belumosudil at 200 mg in the KD025-213 and KD025-208 trials, the most common adverse events of any grade (≥ 20%), including laboratory abnormalities, were infections (53%), asthenia (46%), nausea (42%), diarrhea (35%), dyspnea (33%), cough (30%), decreased lymphocytes (29% grade 2–4), decreased phosphate (28% grade 2–4), edema (27%), hemorrhage (23%), abdominal pain (22%), musculoskeletal pain (22%), headache (21%), hypertension (21%), and increased gamma glutamyl transferase (21% grade 2–4).
The most common grade 3 or 4 adverse events included infection (16%), hypertension (7%), and diarrhea, dyspnea, and hemorrhage (5% each). The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes (13%) and increased gamma glutamyl transferase (11%). Adverse events led to treatment discontinuation in 18%, with the most common event being nausea (4%). One patient died due to adverse events (severe nausea, vomiting, diarrhea, and multiorgan failure).
Belumosudil has warnings/precautions for embryofetal toxicity.
1. Rezurock (belumosudil) tablets prescribing information, Kadmon Pharmaceuticals, LLC, July 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214783s000lbl.pdf. Accessed August 2, 2021.