Biologic and small molecule therapies in chronic spontaneous urticaria: an update

Many new treatment options for chronic spontaneous urticaria have been clinically tested in recent years. This narrative review presents the current status of substances furthest along in development.

After decades in which only H1 antihistamines were available for treatment, omalizumab was approved as an add-on therapy in 2014. Meanwhile, the first omalizumab biosimilar, CT-P39, has been approved (EMA in March 2024, US FDA in March 2025). Moreover, dupilumab received approval in Japan since February 2024 and in the USA since April 2025. Following publication of two positive phase 3 trials, Remibrutinib was submitted for approval to the EMA and FDA in February 2025. Several anti-KIT mAbs are in clinical trials, the most advanced of which is barzolvolimab with two ongoing phase 3 trials. Ligelizumab, benralizumab and the MRGPRX2 antagonist EP-262 are not being further developed in the chronic spontaneous urticaria (CSU) indication.

The rapid increase in clinical trials in the field of CSU has already led to a significant improvement in treatment options beyond anti-IgE therapy with omalizumab in Japan and the USA, and further approvals of biologics and small molecules are expected shortly. It is expected that with a wider range of different approved therapeutic approaches, the treatment of CSU will have to be tailored to the urticaria subtype or patient profile in the future.