Vixarelimab (KPL-716/RO7622888): A Dual Inhibitor of IL-31 and OSM Signaling via OSMRβ – Profile, Clinical Development, and Therapeutic Potential

1. Executive Summary

Vixarelimab, an investigational fully human monoclonal antibody also identified by the development codes KPL-716 and RO7622888/RG6536, is engineered to target the oncostatin M receptor beta (OSMRβ). This specific binding allows Vixarelimab to concurrently inhibit the signaling pathways of two pivotal cytokines: interleukin-31 (IL-31), a principal mediator of pruritus, and oncostatin M (OSM), which is significantly implicated in inflammatory processes, tissue remodeling, and fibrosis.[1] This dual inhibitory mechanism forms the core of its therapeutic rationale across a range of conditions characterized by these pathological features.

Under the initial development by Kiniksa Pharmaceuticals, Vixarelimab (then KPL-716) demonstrated considerable promise in early and mid-stage clinical investigations. A key highlight was the Phase 2a study (NCT03816891) in prurigo nodularis (PN), a chronic and profoundly debilitating skin disorder marked by severe itch and the formation of nodular lesions. In this trial, Vixarelimab achieved its primary efficacy endpoints, delivering statistically significant and clinically meaningful reductions in pruritus intensity and notable improvements in skin lesion appearance.[4] These compelling findings were instrumental in the U.S. Food and Drug Administration (FDA) granting Breakthrough Therapy designation to Vixarelimab for the treatment of pruritus associated with PN.[6]