SWIFT, VOYAGE Trial Updates: New Breakthroughs in Asthma Management

Late-breaking findings presented at the European Respiratory Society (ERS) Congress 2024 unveiled notable advancements in asthma treatment, with a focus on innovative therapies targeting type 2 inflammation.¹

David Jackson, PhD, MSc, is the lead author of the SWIFT-1 and SWIFT-2 trials, professor of respiratory medicine at King’s College London, and clinical lead for severe asthma at Guy’s Hospital and St Thomas’ Hospital. His research on depemokimab revealed substantial reductions in exacerbations and improvements in lung function among patients with severe asthma.

Leonard Bacharier, MD, serves as professor of pediatrics, director of the Center for Pediatric Asthma Research, and scientific director of the Center for Clinical and Translational Research at Vanderbilt University Medical Center. He presented data on dupilumab, demonstrating significant increases in clinical remission rates in children with uncontrolled moderate to severe asthma.

Depemokimab Reduces Severe Asthma Exacerbations by Over 50%

Jackson presented promising findings from a pair of phase 3 trials, SWIFT-1 and SWIFT-2, showing that depemokimab significantly reduced severe asthma exacerbations in patients with uncontrolled eosinophilic asthma.² The trials evaluated the efficacy and safety of depemokimab, a long-acting anti-IL-5 monoclonal antibody, administered only twice a year.

The trials included patients aged 12 and older with a history of asthma exacerbations and elevated eosinophil counts. Depemokimab demonstrated a 58% reduction in exacerbations in the SWIFT-1 trial and a 48% reduction in the SWIFT-2 trial compared with placebo. SWIFT-2 also revealed a 72% reduction in exacerbations requiring hospitalization or emergency department visits (rate ratio, 0.28; 95% CI, 0.13-0.61; P = .002), highlighting monoclonal antibody’s impact on severe outcomes.

Jackson emphasized the rapid onset of effect, presenting a line chart comparing the time to event and the probability of an event between depemokimab and placebo.

“You can already see, way before week 4, there's already separation there,” he explained. “What is also important for all of us clinicians who in the future might be using this drug is the fact that there isn't a narrowing of these 2 lines as you get towards the second dose. There's no suggestion that there's a waning effect. You can see there's continuing separation of the lines as you approach that second dose and as you approach the end of the study, which is very reassuring.”

The trials’ safety data also showed that depemokimab was well-tolerated, with no increase in adverse events. According to Jackson, these findings position depemokimab as a potential game-changer in asthma management, offering significant reductions in exacerbations with only biannual injections.

Dupilumab Increases Clinical Remission Rates in Children With Severe Asthma

New findings on asthma management were presented at the ERS Congress 2024 | Image credit: Mediaphotos – stock.adobe.com

A post-hoc analysis of the Phase 3 VOYAGE study revealed that dupilumab significantly increased clinical remission rates in children with uncontrolled, moderate to severe type 2 asthma.³ During the ERS session, Bacharier highlighted the potential of dupilumab to achieve remission in younger patients with asthma.

In the trial, 408 children aged 6 to 11 years were randomized to receive either a weight-based dose of dupilumab or a placebo over 52 weeks. The study focused on a composite definition of clinical remission, which required:

• The absence of exacerbations or oral corticosteroids
• Normalized lung function defined as a z score > –1.64 for both the prebronchodilator first forced expiratory volume (FEV1) and forced vital capacity (FVC) ratio and prebronchodilator FEV1
• Controlled asthma symptoms based on a 5-item questionnaire score

Results showed that 42% of children receiving dupilumab met the strict criteria for clinical remission compared with only 24% receiving placebo. When a less stringent symptom control measure was used, 46% of the dupilumab group achieved remission compared with 27% of the placebo group.

Importantly, these improvements increased over time, with more children meeting the remission criteria at each 12-week interval.

“At baseline, none of the children met all 3 criteria,” Bacharier said. “Some met 1 or 2, but as time went on, more and more children met more and more criteria for remission, and at all time points—weeks 12, 24, 36, and 52—more children met these criteria while receiving dupilumab compared to placebo.”

According to Bacharier, these results underscore the potential of dupilumab as an effective treatment to help children achieve long-term asthma control, reducing the burden of exacerbations and improving quality of life, while offering hope for pediatric patients.

References

1. Walter K, Costello R. ALERT 2: fighting the burden of asthma and respiratory symptoms. ERS Congress 2024 webinar. Presented September 9, 2024. https://live.ersnet.org/programme/session/92768
2. Jackson DJ, Wechsler ME, Bernstein D, et al. Twice-yearly depemokimab in severe asthma with an eosinophilic phenotype. N Engl J Med. Published online September 9, 2024. doi:10.1056/NEJMoa2406673
3. Maspero JF, Antila MA, Deschildre A, et al. Dupilumab efficacy in children with type 2 asthma receiving high/medium-dose ics (VOYAGE). J Allergy Clin Immunol Pract. Published online August 27, 2024. doi:10.1016/j.jaip.2024.08.038