Itepekimab lowers events indicating loss of asthma control, improves lung function

Treatment with itepekimab resulted in a lower incidence of events indicating loss of asthma control and improved lung function in adults with moderate to severe asthma, according to new phase 2 data.

The phase 2, randomized, double-blind, placebo-controlled, proof-of-concept trial published in The New England Journal of Medicine included 296 adults with moderate to severe asthma (mean age, 49.1 years; 64% women) who were receiving inhaled glucocorticoids plus long-acting beta agonists. Patients were randomly assigned subcutaneous itepekimab 300 mg (Sanofi/Regeneron; n = 73), dupilumab 300 mg (Dupixent, Sanofi/Regeneron) plus itepekimab 300 mg (n = 74), dupilumab 300 mg (n = 75) or placebo (n = 74) every 2 weeks for 12 weeks. Patients discontinued LABA at 4 weeks following randomization and tapered inhaled glucocorticoids over weeks 6 to 9.

“Severe asthma remains a big problem, and there are many patients who continue to have poor asthma control despite standard of care therapy and even advanced biologics,” Michael E. Wechsler, MD, of the department of medicine at National Jewish Health, Denver, told Healio. “There is a need to identify new therapies and [interleukin]-33 is a rational target based on its known role as an epithelial alarmin that responds to a variety of different stimuli.”

The primary outcome was an event that indicated loss of asthma control among patients assigned itepekimab alone and itepekimab plus dupilumab. Secondary outcomes included lung function, asthma control, quality of life, type 2 biomarkers and safety.

At 12 weeks, an event indicating loss of asthma control occurred in 41% of the placebo group compared with 22% of patients in the itepekimab-only group (OR = 0.42 vs. placebo; 95% CI, 0.2-0.88; P = .02), 27% of the itepekimab plus dupilumab group (OR = 0.52; 95% CI, 0.26-1.06; P = .07) and 19% of the dupilumab-alone group (OR = 0.33; 95% CI, 0.15-0.7).

Compared with placebo, pre-bronchodilator FEV₁ increased among patients in the itepekimab-alone (mean difference = 0.14; 95% CI, 0.01-0.27) and dupilumab-alone (mean difference = 0.16; 95% CI, 0.03-0.29) groups but not in the itepekimab plus dupilumab group (mean difference = 0.1; 95% CI, –0.03 to 0.23).

In addition, the researchers reported improvements in asthma control and quality of life with itepekimab, compared with placebo, leading to strong reductions in mean blood eosinophil count.

Adverse events were reported among 70% of patients in the itepekimab-alone group, itepekimab plus dupilumab group and placebo group and in 66% of patients in the dupilumab-alone group. Among patients in the itepekimab alone and itepekimab plus dupilumab groups, compared with placebo, the most common adverse events reported were nasopharyngitis (18% and 11% vs. 12%, respectively), allergic rhinitis (4% and 0% vs. 1%), nausea (5% and 3% vs. 3%) and back pain (5% and 3% vs. 1%).

“We need to identify which patients are most likely to respond to this therapy and why combination therapy with anti-[interleukin]-4 dupilumab did not achieve optimal results,” Wechsler said.

For more information:

Michael E. Wechsler, MD, can be reached at mikewechsler@gmail.com