Lirentelimab is an anti-sialic acid-binding immunoglobulin-like lectin 8 mAb that selectively inhibits mast cells and depletes eosinophils. It is being studied for chronic urticaria that is often refractory to standard therapy.
Chronic urticaria is a mast cell disease that causes recurrent itching, hives and angioedema for more than 6 weeks. It can occur spontaneously or caused by sweat inducing exercise or by minor stroking, rubbing or scratching the skin, dermographism.
First line therapy is oral H1-antihistamines up to 4x day. However there remains many refractory cases. Xolair is the next step in therapy. However there still remains patients who do not respond to therapy. Severe Hives Treatment (Xolair and Cyclosporine)
Siglec-8 is an inhibitory receptor expressed on mast cells and eosinophils. Engagement of this receptor has been shown to inhibit mast cell activation.
Lirentelimab (AK002) is an investigational medicine, first in class, humanized monoclonal antibody against Siglec-8. Its been shown to suppress mast cell activity in inflammatory pathways and deplete eosinophils. Lirentelimab has been evaluated in trials with those who have eosinophilic GI disorders and conjunctivitis and systemic mastocytosis.
A recent phase 2 study enrolled patients with refractory chronic urticaria who failed 4 X day of H1 antihistamines. Patients received 6 monthly infusions of lirentelimab. Urticarial Control Test scores improved with lirentelimab across all dosages. In addition, lirentelimab treatment led to improved signs and symptoms by the Hives Severity Score and Itch Severity Score for patients who failed Xolair. Side effects were minimal and there were no drug related serious adverse events.
This was a small sample size and more studies are needed, but lirentelimab may be a promising treatment option for patients who fail other drug measures. By binding directly to mast cells and inhibiting them, lirentelimab is using a novel approach to decrease the release of histamine in chronic urticaria patients. This treatment may also possibly be used to treat other allergic diseases in the future as well.