Itepekimab monotherapy improves lung function in patients with moderate-to-severe asthma: NEJM

Asthma is a major non-communicable disease that needs immediate attention and management. Over 262 million people are affected with asthma. Monoclonal antibodies targeting IgE, interleukin-4 and -13, and interleukin-5 are effective in treating severe type 2 asthma, but new targets are essential to manage asthma.

Itepekimab was safe and effective alternative treatment for patients suffering from moderate-to-severe asthma, reveal results of a phase 2 trial by Michael E. Wechsler, MD, MMSc, director of the National Jewish Health Cohen Family Asthma Institute and colleagues.

Itepekimab is a new monoclonal antibody against the upstream alarmin interleukin-33. 

The findings of the study are published in The New England Journal of Medicine.

The objective of the study was to evaluate efficacy and safety of itepekimab as monotherapy, as well as in combination with dupilumab, in patients with asthma as their role remains unclear.

The study was a phase 2 trial, randomly assigned, in a 1:1:1:1 ratio, adults with moderate-to-severe asthma receiving inhaled glucocorticoids plus long-acting beta-agonists (LABAs) to receive subcutaneous itepekimab (300 mg), itepekimab plus dupilumab (300 mg; combination therapy), dupilumab (300 mg), or placebo every 2 weeks for 12 weeks. After randomization, LABA was discontinued at week 4, and inhaled glucocorticoids were tapered over weeks 6 through 9. The primary end point was an event indicating a loss of asthma control. Secondary and other end points included lung function, asthma control, quality of life, type 2 biomarkers, and safety.

The results of the study were

• A total of 296 patients underwent randomization. By 12 weeks, an event indicating a loss of asthma control occurred in 22% of the patients in the itepekimab group, 27% of those in the combination group, and 19% of those in the dupilumab group, and 41% in those of placebo group

• The corresponding odds ratios as compared with placebo were as follows: in the itepekimab group, 0.42; in the combination group, 0.52 and 0.33 in dupilumab group.

• As compared with placebo, the forced expiratory volume in 1 second before bronchodilator use increased with the itepekimab and dupilumab monotherapies but not with the combination therapy.

• Itepekimab treatment improved asthma control and quality of life, as compared with placebo, and led to a greater reduction in the mean blood eosinophil count. The incidence of adverse events was similar in all four trial groups.

Dr Wechsler and team concluded that "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."

Reference:

DOI: 10.1056/NEJMoa2024257