An investigational monoclonal antibody, barzolvolimab, has demonstrated significant efficacy in treating chronic inducible urticaria, specifically cold urticaria and symptomatic dermographism. Results from a phase II trial presented at the American College of Allergy, Asthma & Immunology (ACAAI) annual meeting reveal that barzolvolimab significantly improved provocation test outcomes and reduced symptoms compared to placebo.
The double-blind, randomized trial involved 96 patients with cold urticaria and 97 with symptomatic dermographism, all of whom had been diagnosed for over 3 months and experienced recurrent wheals despite antihistamine use. Participants were randomized to receive either barzolvolimab (150 mg every 4 weeks or 300 mg every 8 weeks) or placebo subcutaneously over a 20-week period, followed by a 24-week follow-up.
Primary Endpoint Success
The primary endpoint was the percentage of patients achieving a complete response (CR) at week 12, defined by a negative provocation test. For cold urticaria, this meant no reaction to 4°C on the TempTest, while for symptomatic dermographism, it meant no wheal response to the FricTest. The results showed a marked improvement in CR rates with barzolvolimab.
In the cold urticaria group, CR rates reached 46.9% with the 150-mg dose and 53.1% with the 300-mg dose, compared to 12.5% with placebo (P = 0.0023 and P = 0.0011, respectively). For symptomatic dermographism, CR rates were 57.6% with the 150-mg dose and 42.4% with the 300-mg dose, versus 3.2% with placebo (P < 0.0001 and P = 0.0003).
Additional Benefits and Safety
Beyond the primary endpoint, the study also assessed secondary endpoints, including itch reduction and improvements in the urticaria control test (UCT). Barzolvolimab was effective at reducing itch at the time of provocation compared to placebo in both groups. The UCT scores also improved, indicating better overall control of hives.
According to Jonathan Bernstein, MD, of the University of Cincinnati Medical Center, the study demonstrated clinical benefit in patients with chronic inducible urticaria, a condition for which there are currently no approved therapies beyond antihistamines. He noted that improvements were observed as early as 2 weeks after the first dose.
The safety profile of barzolvolimab was consistent with previous studies. The majority (98%) of treatment-emergent adverse events (AEs) were grade 1 or 2, and there were no significant differences in discontinuation rates between the barzolvolimab and placebo groups. Common AEs included neutropenia (10% with barzolvolimab vs none with placebo) and hair color changes (13% with barzolvolimab vs none).
Mechanism of Action and Future Directions
Chronic inducible urticaria is a mast cell-driven disease triggered by cold temperatures or pressure on the skin. Barzolvolimab inhibits the activation of KIT by stem cell factors, which are crucial for the survival and activity of mast cells. By targeting KIT, barzolvolimab aims to reduce the underlying inflammation and symptoms associated with chronic inducible urticaria.
Phase III trials are planned for chronic inducible urticaria, building on the promising results from this phase II study. The estimated completion date for the phase II study is September 2025.
