Treatment Outperforms Placebo for Asthma Control, Lung Function Gains

Events indicating a loss of asthma control were lower with itepekimab than placebo in adults with moderate-to-severe asthma, according to a study published in The New England Journal of Medicine.

“Monoclonal antibodies targeting IgE, interleukin-4 and -13, and interleukin-5 are effective in treating severe type 2 asthma, but new targets are needed,” wrote an international team of researchers. “Itepekimab is a new monoclonal antibody against the upstream alarmin interleukin-33.”

The phase 2 trial, funded by Sanofi and Regeneron Pharmaceuticals, investigated the efficacy and safety of itepekimab alone and combined with dupilumab. Some 296 patients with moderate-to-severe asthma receiving inhaled glucocorticoids plus long-acting beta-agonists (LABAs) were randomly assigned 300 mg subcutaneous itepekimab, 300 mg itepekimab plus 300 mg dupilumab, 300 mg dupilumab, or placebo every 2 weeks for 12 weeks. At week 4, LABAs were stopped, and inhaled glucocorticoids were tapered over weeks 6 through 9.

An event indicating a loss of asthma control, the study’s primary end point, occurred in 22% of the patients in the itepekimab group, 27% in the combination group, 19% in the dupilumab group, and 41% in the placebo group by week 12. Compared with placebo, corresponding odds ratios for an event indicating a loss of asthma control were 0.42 with itepekimab, 0.52 with itepekimab combined with dupilumab, and 0.33 with dupilumab, researchers reported.

Furthermore, the forced expiratory volume in 1 second before bronchodilator use increased with the itepekimab monotherapy and dupilumab monotherapy, but not with itepekimab combined with dupilumab, compared with placebo, according to the study. Asthma control and quality of life improved, and mean blood eosinophil count decreased more, with itepekimab vs placebo.

Adverse events occurred at similar rates in each group.

“Interleukin-33 blockade with itepekimab led to a lower incidence of events indicating a loss of asthma control than placebo and improved lung function in patients with moderate-to-severe asthma,” investigators concluded.

Reference:
Wechsler ME, Ruddy MK, Pavord ID, et al. Efficacy and safety of itepekimab in patients with moderate-to-severe asthma. N Engl J Med. 2021;385(18):1656-1668. doi:10.1056/NEJMoa2024257