Vixarelimab

Vixarelimab is a fully humanized monoclonal antibody with a novel mechanism of action. Its action targets two major causes of prurigo, pruritus and cutaneous fibrosis(IL-31 and OSM type II receptor signaling). The OSM signaling pathway contributes to the pathogenesis of fibrosis, and blocking this pathway could have an impact on cutaneous fibrosis and an additional effect beyond the relief of itching.

Vixarelimab is in clinical development by Genentech USA and is currently in Phase II for chronic prurigo. Other potential indications include: pruritus, plaque psoriasis (psoriasis vulgaris), lichen simplex chronicus (atopic dermatitis), erosive oral lichen planus, atopic dermatitis, idiopathic pulmonary fibrosis, interstitial lung disease, ulcerative colitis and fibrosis. Vixarelimab is administered intravenously and subcutaneously.

Two cytokines, interleukin 31 (IL-31) and oncostatin M (OSM), play a central role in the pathophysiology of prurigo nodularis

- IL-31 as the main mediator of itching

and

-OSM as a mediator of skin inflammation, hyperkeratosis and fibrosis.

The intensity of itching correlates with the amount of dermal IL-31 (+), IL-31RA (+) and OSM (+) cells; the number of dermal OSM receptor β-cytokine receptor subunit (OSMRβ) (+) cells is also increased in prurigo patients (Hashimoto T et al. 2021).

Vixarelimab does not affect hematologic parameters. This probably reflects the specific effect on the type II OSM receptor, as only OSMRß is bound. In contrast, the monoclonal anti-OSM antibody GSK2330811, which non-specifically blocks all OSM signaling, led to dose-dependent thrombocytopenia in healthy volunteers.

1. Hashimoto T et al. (2021) Itch intensity in prurigo nodularis is closely related to dermal interleukin-31, oncostatin M, IL-31 receptor alpha and oncostatin M receptor beta. Exp Dermatol 30:804-810.