Theresa W. Guilbert, MD, MS

Credit: cincinnatichildrens.org

Dupilumab may help to substantially lower annualized rates of severe exacerbations for asthma and help to improve lung functioning among children, according to new data presented at the European Respiratory Society (ERS) International Congress 2023 in Milan.¹

This new study’s investigators noted that younger patients known to have persistent cases of asthma frequently deal with the hardship of diminished lung function, and this can negatively impact their life quality and increase their risk of asthma exacerbations.

The phase 3 LIBERTY ASTHMA VOYAGE clinical trial was conducted with the purpose of investigating the effects of the investigational drug dupilumab and discovering whether it would be a promising option for such patients.

Dupilumab, a fully-human monoclonal antibody, is known to inhibit interleukin-4 (IL-4) and interleukin-13 (IL-13). Its use has also recently been tested for individuals with chronic obstructive pulmonary disease (COPD) and Type 2 (T2) inflammation.²

Background and Findings

The principal objectives of the LIBERTY ASTHMA VOYAGE study were to look at how well lung function would end up responding at both 12 weeks (‘Wk12’) and 52 weeks (‘Wk52’) within the VOYAGE study.

The team’s research involved a set of children participants in the age range of 6 - 11 years who were facing uncontrolled, moderate-to-severe type 2 asthma. The study’s inclusion criteria were defined through the use of specific biomarker measurements: baseline (BL) blood eosinophils of ≥150 cells/μL or fractional exhaled nitric oxide levels ≥20 ppb.

For the research team’s investigation, the participants were randomly placed into groups to either be given dupilumab at 100mg or 200mg doses, and the dosages were determined based on participant body weight and administered every 2 weeks. Alternatively, the other group would be given a volume-matched placebo for the totality of the 52-week study timeframe.

The investigators' results were exceptionally promising, as the findings showed a major enhancement in lung function following the initiation of dupilumab treatment as opposed to those in the placebo arm.

At 12 weeks, the team noted a statistically significant rise in the least squares mean (LSM) change from the point of baseline in % predicted pre-BD FEV1 (ppFEV1) of 5.20 (95% CI: 2.14–8.26; P= 0.0009), and this was in favor of dupilumab.

The notable positive trend was shown by the investigators to have continued at the 52-week mark, at which point an even more substantial LSM difference of 7.79 (95% CI: 4.36–11.22; P<0.0001) was reported by the investigators between the dupilumab and placebo arms of the study.

The investigators also looked at the proportion of study participants who were able to see a substantial improvement in ppFEV1, defined as an increase of 10% minimum, at both 12 and 52 weeks. The drug showed its effectiveness in this regard as well.

By the 12-week mark, 44.9% of patients receiving dupilumab achieved this level of improvement, compared to 31.6% in the placebo group (P=0.0173). By 52 weeks, they found the gap had widened even more, with 47.5% of dupilumab-treated individuals meeting the ≥10% ppFEV1 improvement criteria, versus only 28.1% in the placebo arm (P=0.0006).

Furthermore, the study explored the annualized rate of severe exacerbations in patients who met the ≥10% ppFEV1 improvement threshold. They found that the results were compelling, indicating a major reduction in participants’ rate in the dupilumab arm versus placebo: 0.304 vs. 0.744 (P=0.0103), respectively.

Overall, the team’s reported outcomes in the VOYAGE trial indicated the strong potential of dupilumab for enhancement of lung function among children facing uncontrolled type 2 asthma.

References

1. ^{Theresa W. Guilbert, MD, MS, et al. Dupilumab Shows Promise in Improving Lung Function in Children with Asthma. Paper presented at: European Respiratory Society (ERS) International Congress 2023; September 9 – 13. Milan, Italy. Accessed September 15, 2023.}
2. ^{Surya P Bhatt, MD, et al. Efficacy and Safety of Dupilumab for COPD with Type 2 Inflammation Indicated by Elevated Eosinophils. Paper presented at: European Respiratory Society (ERS) International Congress 2023; September 9 – 13. Milan, Italy. Accessed September 14, 2023.}