Positive Phase 3 Findings Identified for Depemokimab Treatment of Severe Asthma

Depemokimab treatment of severe asthma leads to a reduction of serious attacks by over 50% and a 72% reduction of exacerbations leading to hospitalization, according to new findings.¹

These new phase 3 data were presented at the European Respiratory Society and were published in The New England Journal of Medicine on September 9. The findings were the conclusion of the late-stage SWIFT-1 and SWIFT-2 studies.^1,2

Depemokimab was formulated as an ultra-long-acting biologic treatment of severe asthma, administered 2 times per year at 6-month intervals. The drug has an enhanced binding affinity for interleukin (IL)-5.

“These results add to the established body of evidence that targeted inhibition of IL-5 plays a key role in reducing type 2 inflammation that drives severe asthma exacerbations,” Kaivan Khavandi, GSK’s global head of Respiratory/Immunology R&D, said in a statement. “Depemokimab could offer the possibility of sustained inhibition of this pathway, with a dosing schedule of just two injections per year.”²

Severe asthma is characterized by the need for high-dose inhaled corticosteroids in addition to a second controller medication. It may also require systemic corticosteroids or biologics to control the condition, though asthma may remain uncontrolled despite such management strategies.¹

The pulmonary condition is also associated with type 2 inflammation among over 80% of patients. Increased levels of eosinophils, a type of white blood cell, are commonly observed in such cases and eosinophil counts can be assessed using a blood test.

IL-5, as well as IL-4 and IL-13, is a key protein involved in type 2 inflammation, and IL-5 specifically is known to support the function, growth, and longevity of eosinophils.

In the SWIFT-1 and SWIFT-2 trials, a set of phase 3A randomized, placebo-controlled studies, the research teams assessed individuals with severe cases of eosinophilic asthma. Those participating had eosinophil levels which were elevated, at ≥300 cells per microliter in the prior year or ≥150 cells per microliter at the time of their screening. They also had a reported history of exacerbations despite using medium- or high-dose inhaled glucocorticoids.¹

The investigators’ main goals were to assess the annualized rate of asthma exacerbations over the course of 52 weeks. In terms of secondary outcomes assessed in the study, the team analyzed them hierarchically and looked at shifts in forced expiratory volume in 1 second (FEV1), St. George’s Respiratory Questionnaire (SGRQ) scores, and patient-reported asthma symptoms at the 52-week mark.

During the studies, the 762 subjects in the 2 studies were randomly assigned in a 2:1 ratio to be given either 100 mg of depemokimab using a subcutaneous injection or a placebo at the 0 and 26-week marks, in addition to standard care. 502 such participants were assigned to be given depemokimab, and 260 were placed in the placebo arm.

The yearly exacerbation rate in SWIFT-1 was found by the investigators to be 0.46 (95% confidence interval [CI], 0.36 - 0.58) for those treated with depemokimab, compared to 1.11 (95% CI, 0.86 to 1.43) in the placebo arm. The resulting rate ratio was 0.42 (95% CI, 0.30 to 0.59; P < .001).

In SWIFT-2, the research team concluded that the exacerbation rate was 0.56 (95% CI, 0.44 - 0.70) for those in the treatment arm and 1.08 (95% CI, 0.83 - 1.41) for the placebo arm. This led to a rate ratio of 0.52 (95% CI, 0.36 - 0.73; P < .001). There were no substantial distinctions observed between the 2 cohorts in terms of changes from the point of baseline in patients’ SGRQ scores.

They also found that the incidence of adverse events was shown to be comparable between the depemokimab and placebo cohorts within both trials.

“This is important as research shows that 73% of physicians believe longer dosing intervals would be beneficial to patients who are often juggling multiple therapies,” Khavandi said in a statement.¹

References

1. ^{Jackson DJ, Wechsler ME, Chen R, et al. Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype. The New England Journal of Medicine. September 9, 2024. https://www.nejm.org/doi/full/10.1056/NEJMoa2406673. Date accessed: September 9, 2024.}
2. ^{GSK announces positive results from phase III severe asthma trials of depemokimag. GSK. May 21, 2024. https://www.gsk.com/en-gb/media/press-releases/gsk-announces-positive-results-from-phase-iii-severe-asthma-trials-of-depemokimab/. Date accessed: September 9, 2024.}