What is the mechanism of action of Vixarelimab?

October 8, 2025 •

3 min read

Vixarelimab is being investigated for conditions involving itch and inflammation. A key aspect is understanding the unique dual mechanism of action of Vixarelimab.

Quick Summary

Vixarelimab is a fully human monoclonal antibody that blocks the signaling of both interleukin-31 (IL-31) and oncostatin M (OSM) by binding to the shared oncostatin M receptor beta (OSMRβ).

Key Points

Dual Cytokine Inhibition: Vixarelimab simultaneously blocks the signaling of two key cytokines, interleukin-31 (IL-31) and oncostatin M (OSM).
Single Receptor Target: Its action is achieved by binding to the oncostatin M receptor beta (OSMRβ) subunit, which is a shared component of both the IL-31 and OSM receptor complexes.
Blocks Itch and Inflammation: By inhibiting IL-31 signaling, Vixarelimab reduces pruritus (itching); by inhibiting OSM, it addresses the underlying inflammation, hyperkeratosis, and fibrosis.
Interrupts the Itch-Scratch Cycle: This dual mechanism is particularly effective against diseases like prurigo nodularis, which are driven by a cycle of itching and scratching that leads to chronic skin damage.
Potential for Fibrotic Diseases: Beyond dermatological conditions, Vixarelimab’s ability to inhibit OSM-related fibrosis makes it a potential candidate for treating fibrotic diseases like idiopathic pulmonary fibrosis.
Specific Action: The drug selectively targets the OSMRβ pathway and does not interfere with the separate OSM type I receptor complex involved in hematopoiesis, avoiding potential adverse effects on blood cell production.

A Dual Inhibitor Targeting a Shared Receptor

Vixarelimab is a fully human monoclonal antibody currently under investigation for therapeutic use. Its mechanism of action centers on targeting and binding to the oncostatin M receptor beta (OSMRβ). This receptor subunit is a shared component of two different cytokine receptor complexes involved in inflammatory skin diseases.

By binding to OSMRβ, Vixarelimab acts as a dual inhibitor, blocking the signaling of both interleukin-31 (IL-31) and oncostatin M (OSM). This dual inhibition is particularly relevant for conditions like prurigo nodularis, which involve multiple factors.

The Role of OSMRβ in Signaling

OSMRβ is part of two important receptor complexes:

Interleukin-31 (IL-31) Receptor: This complex forms when OSMRβ combines with the IL-31 receptor alpha chain (IL-31Rα). It is primarily responsible for the intense itching (pruritus) seen in some skin conditions. Vixarelimab's action on OSMRβ disrupts this complex, thereby interrupting itch signals.
Oncostatin M (OSM) Type II Receptor: This receptor is formed by OSMRβ and glycoprotein 130 (gp130). The OSM pathway is linked to inflammation, skin thickening (hyperkeratosis), and scar tissue formation (fibrosis). By inhibiting this pathway, Vixarelimab can help reduce these effects.

Targeting the Itch-Scratch Cycle

Vixarelimab's mechanism is effective in breaking the itch-scratch cycle common in chronic inflammatory skin diseases. IL-31 causes itching, leading to scratching, which damages the skin. This damage can trigger inflammation, partly driven by OSM. By blocking both pathways, Vixarelimab addresses both the itching and the resulting skin damage.

Comparison with Other Therapeutic Approaches

This table illustrates how Vixarelimab's dual mechanism may offer broader benefits compared to treatments that target only a single pathway.


Feature	Vixarelimab	Anti-IL-31RA Monoclonal Antibody (e.g., Nemolizumab)	Traditional Systemic Therapy (e.g., Immunosuppressants)
Mechanism	Dual inhibition of IL-31 and OSM signaling.	Specific inhibition of IL-31 signaling only.	Broad suppression of the immune system.
Primary Target	Oncostatin M receptor beta (OSMRβ).	IL-31 receptor alpha chain (IL-31Rα).	Non-specific immune cells and cytokines.
Effect on Itch	Directly addresses pruritus by blocking IL-31 signaling.	Directly addresses pruritus by blocking IL-31 signaling.	Indirectly reduces itch by suppressing inflammation.
Effect on Nodules	Targets underlying inflammation and fibrosis associated with nodule formation through OSM inhibition.	Primarily focuses on reducing the itch, with less direct effect on inflammation/fibrosis.	Reduces inflammation but may not specifically address fibrotic processes as effectively.
Potential Side Effects	Generally well-tolerated in trials, with no major drug-related signals reported in early studies.	Specific to IL-31 inhibition.	Risk of broad immunosuppression, potential for infections and other systemic side effects.

The Specificity of Vixarelimab

Vixarelimab exhibits specificity in its action. Oncostatin M can also signal through the OSM type I receptor, which involves gp130 and LIFR and is important for blood cell production. Vixarelimab does not inhibit this pathway, helping to avoid potential side effects on blood cell production.

Potential Therapeutic Implications

Beyond prurigo nodularis, Vixarelimab's dual mechanism holds promise for other conditions involving itching, inflammation, and fibrosis. It is being investigated for diseases like idiopathic pulmonary fibrosis and systemic sclerosis-associated interstitial lung disease. By addressing both symptomatic and underlying pathological factors, Vixarelimab could be a significant treatment for various debilitating diseases.

Conclusion

In conclusion, Vixarelimab is a fully human monoclonal antibody that targets the shared oncostatin M receptor beta (OSMRβ) subunit. This action effectively blocks the signaling of both IL-31 and OSM, thereby addressing both pruritus and the inflammatory and fibrotic skin lesions characteristic of conditions such as prurigo nodularis. For more in-depth clinical trial data and information, refer to publications on the {Link: National Institutes of Health website https://pmc.ncbi.nlm.nih.gov/articles/PMC9932343/}.

Frequently Asked Questions

Vixarelimab is a fully human monoclonal antibody that is under investigation for treating chronic inflammatory and fibrotic diseases. It works by targeting a specific receptor subunit to block inflammatory signals.

It inhibits itching by binding to the OSMRβ receptor subunit, which prevents the signaling of interleukin-31 (IL-31). IL-31 is a cytokine known to be a primary mediator of pruritus, or intense itching.

Inhibiting oncostatin M (OSM) signaling is crucial because OSM promotes inflammation, hyperkeratosis (skin thickening), and fibrosis (scarring). By blocking this pathway, Vixarelimab helps resolve the skin lesions associated with diseases like prurigo nodularis.

IL-31 and OSM are both cytokines, but they initiate different but related pathways involved in skin diseases. IL-31 is strongly associated with the itching sensation, while OSM is a key driver of skin inflammation and fibrosis.

By targeting the shared OSMRβ subunit, Vixarelimab can inhibit both the IL-31 and OSM pathways simultaneously with a single antibody. This offers a broader therapeutic approach than targeting only the IL-31 receptor alpha chain (IL-31Rα).

Vixarelimab has been primarily studied for prurigo nodularis. Its potential is also being explored for other fibrotic and systemic inflammatory diseases, including idiopathic pulmonary fibrosis and systemic sclerosis-associated interstitial lung disease.

Vixarelimab is an investigational drug and is not yet approved by regulatory bodies like the FDA for general use. It has received Breakthrough Therapy designation for prurigo nodularis, which facilitates its development and review.

Clinical trials for Vixarelimab have used subcutaneous injection (under the skin) as the method of administration.