Could the anti-IL-33 monoclonal antibody ittepekimab be a treatment option for moderate to severe chronic obstructive pulmonary disease (COPD)? That's what researchers investigated in a study of the antibody's efficacy, safety and tolerability. The results were published in the journal The Lancet Respiratory Medicine.
Genetic data suggest that interleukin 33 (IL-33) - a substance in the immune system - plays a role in asthma susceptibility. It may also be important in COPD. Previous studies showed, for example, that blood levels of IL-33 are elevated during acute exacerbations.
DZL scientists and researchers first conducted genetic studies to determine whether genetic variants within the IL-33 pathway are associated with risk for COPD. They found that genetic variants that resulted in a loss of function of IL-33 had a lower risk of developing COPD. Variants that resulted in IL-33 being more active had an increased risk of COPD. An indication that IL-33 may indeed play a role in COPD.
Therefore, in the second part of this Phase IIa study, they investigated the safety and efficacy of the antibody Itepekimab in moderate to severe COPD. Itepekimab targets IL-33, inhibiting the activity of the protein. 343 patients aged 40 to 75 years were enrolled in the study. All were current or former smokers with a diagnosis of COPD for at least one year. They were randomly assigned to either the Itepekimab or placebo group. Individuals in the Itepekimab group received - in addition to standard therapy - the antibody as injections every two weeks. The other group received a drug-free placebo instead of the antibody. The effect of Itepekimab on the annual rate of acute exacerbations of COPD and on lung function was analyzed.
Initially, no significant differences were seen when comparing the two groups. However, subgroup analysis showed that Itepekimab significantly reduced the rate of exacerbations and improved lung function in former smokers with COPD. The beneficial effects persisted during the 20-week post-treatment follow-up period. Side effects were about the same in both groups.
Although the study showed no benefit of Itepekimab for current smokers with COPD, the authors said. However, for former smokers with COPD, this biologic therapy could be an option to improve rates of disease exacerbation and lung function. Upcoming trials should therefore focus even more on this subgroup of patients. Two phase 3 clinical trials with DZL participation are already underway to confirm and further understand the potential of the novel therapy in former smokers with COPD.
Original publication: Rabe KF et al., 2021 / The Lancet