Urticaria and angio-oedema - Emerging treatments

Berotralstat

Berotralstat is an oral plasma kallikrein inhibitor. Berotralstat is approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for prophylaxis to prevent attacks of hereditary angio-oedema (HAE) in adults and paediatric patients 12 years and older, and is recommended first-line for long-term prophylaxis for patients with HAE by some guidelines.[36] Results from phase 2 and 3 studies demonstrated reduction in the attack rate and on-demand usage in patients treated with oral berotralstat for long-term prophylaxis of HAE.[81][82] In the UK, the National Institute for Health and Care Excellence (NICE) recommends berotralstat as an option for preventing recurrent attacks of HAE in people 12 years and older who have at least 2 attacks per month.[83] Use of berotralstat is conditional upon the company providing berotralstat according to the commercial arrangement. NICE recommends that berotralstat is stopped if the number of attacks per month does not reduce by at least 50% after 3 months.[83]

Lanadelumab

Lanadelumab is a monoclonal antibody plasma kallikrein inhibitor. Lanadelumab is approved by the FDA and EMA for prophylaxis to prevent attacks of HAE in adults and paediatric patients 2 years and older (in the US) and 12 years and older (in Europe), and is recommended first-line for long-term prophylaxis for patients with HAE by some guidelines.[36] During one 26-week randomised controlled trial, lanadelumab reduced the rate of acute attacks, the number of moderate or severe attacks per month, and the need for rescue treatment, compared with placebo, in patients with HAE.[84] The majority of reported adverse effects related to injection site pain. An open-label extension study to assess longer-term safety and efficacy is in progress.[85]

STAR-0215

STAR-0215, an investigational monoclonal antibody plasma kallikrein inhibitor, has received fast track designation from the FDA for the treatment of HAE. Phase 1a and phase 1b/2 trials for healthy adults and patients with HAE respectively are recruiting.[86][87]

Ligelizumab

Ligelizumab is a high-affinity humanised monoclonal anti-IgE antibody. One phase 2 trial demonstrated that, at 12 weeks, a higher percentage of chronic spontaneous urticaria patients treated with ligelizumab had complete control of symptoms compared with patients receiving omalizumab or placebo.[88] Further research is needed to determine the optimal dosing strategy and establish the clinical efficacy of ligelizumab.