Belumosudil (Rezurock®): A Comprehensive Monograph on the First-in-Class Selective ROCK2 Inhibitor for Chronic Graft-Versus-Host Disease

1.0 Executive Summary

Belumosudil, marketed under the brand name Rezurock®, is a first-in-class, orally administered small molecule that functions as a selective inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2). Its approval by the U.S. Food and Drug Administration (FDA) marks a significant advancement in the therapeutic landscape for chronic graft-versus-host disease (cGVHD), a severe, multi-system complication following allogeneic hematopoietic cell transplantation. Belumosudil is specifically indicated for the treatment of adult and pediatric patients aged 12 years and older with cGVHD who have experienced treatment failure after at least two prior lines of systemic therapy.[1] This indication addresses a critical unmet medical need in a patient population with limited effective options and substantial morbidity.

The therapeutic efficacy of Belumosudil is rooted in its novel mechanism of action, which uniquely targets the dual pathology of cGVHD: dysregulated inflammation and progressive fibrosis.[4] By selectively inhibiting ROCK2, Belumosudil orchestrates a sophisticated immunomodulatory effect, rebalancing the critical ratio of pro-inflammatory T helper 17 (Th17) cells to anti-inflammatory regulatory T (Treg) cells. This is achieved through the differential modulation of the STAT3 and STAT5 signaling pathways.[5] Concurrently, Belumosudil exerts a direct anti-fibrotic effect by inhibiting downstream pathways that lead to collagen deposition and tissue scarring.[5]