Itepekimab is an anti-Il-33 monoclonal. Il-33 is an epithelium-derived cytokine that promotes Th2 immune responses in response to cellular damage with roles in asthma and COPD (Chronic Obstructive Pulmonary Disease).
Two randomized controlled clinical trials were performed assessing the efficacy of Itepekimab in asthma and COPD.
After identifying the asthma associated variants in the genes encoding IL-33 or its receptor IL1RL1, also modifying the risk of COPD, the investigators performed a phase 2 placebo-controlled trial in patients with moderate to severe COPD. This study published in the Lancet. Itepekimab did not reduce the annualized rate of exacerbations overall but did so in a prespecified subgroup of former smokers.
Published in The New England Journal of Medicine, investigators performed a phase 2 placebo controlled trial assessing itepekimab in combination with dupilumab, which inhibits the downstream signaling pathways of both Il-4 and IL-13, in patients with moderate to severe asthma. The combination of of itepekimab and dupilumab reduced the incidence of loss of asthma control and improved lung function, but were not superior to each drug alone.
These studies highlight the potential of targeting IL-33 in COPD and asthma.
The last several years many new biological drugs have been released for asthma. Targeted therapy is being used for particular patients. In the past for asthma, it was just a “one sized fits all” approach for asthma, all patient were usually given a steroid inhaler as first line approach. But over the years, different subtypes of asthma have been discovered. For patients with allergic asthma, Xolair is given for patients who have an elevated IgE.
For patients with eosinophilic asthma, there are 3 medications currently available, Nucala, Fasenra and Cinqair.
For patients with steroid dependent asthma and eosinophilic asthma, Dupixent is another biologic. And for patients with “other” types of asthma, Tezspire can be used.
Itepekimab may be a choice in the future for patients who have associated issues with IL-33 or its receptor. Currently there is no commercial testing to check patients who have abnormalities with those biomarkers, but it could be potentially be tested and used in the future.