Twice-yearly depemokimab for asthma tolerated well as exacerbation rates fall
Key takeaways:
- Depemokimab’s mechanism of action is similar to mepolizumab.
- Three adverse events led to discontinuation or withdrawal.
- 72% of patients were exacerbation-free, and 96% did not need a hospital or ED visit.
SAN DIEGO — Patients with asthma who used depemokimab tolerated treatment well while experiencing reductions in rates of clinically significant exacerbations, according to a poster abstract presented here.
“It’s an ultra-long-acting anti-IL5 agent, meaning that it can be dosed every 6 months, rather than the more frequent dosing that prior biologics have used,” Daniel J. Jackson, MD, professor of pediatrics, University of Wisconsin-Madison, told Healio at the 2025 American Academy of Allergy, Asthma & Immunology/World Allergy Organization Joint Congress.
“This really has the same mechanism of action as mepolizumab,” he continued. “The goal is to alter dosing, which can improve adherence and be easier for patients and families.”
In the previous phase 3 SWIFT-1/2 studies, two doses of depemokimab (GSK) administered at week 0 and 26 in addition to standard of care reduced asthma exacerbations by approximately 50% compared with placebo at week 52, Jackson said.
Patients who received depemokimab and placebo during SWIFT-1/2 all received 100 mg subcutaneous doses of the biologic at weeks 0 and 26 in addition to standard of care in the phase 3 AGILE study.
“Everyone in this long-term extension was on active therapy,” Jackson said.
The cohort included 629 patients (60% female; 78% white; 57% European) aged 12 years and older (mean age, 54.8 years), with 419 who received depemokimab and 210 who received placebo in SWIFT-1/2.
Also, these patients had been diagnosed with asthma for a mean of 22.7 years at the SWIFT-1/2 baseline, with 268 (43%) receiving medium doses and 361 (57%) receiving high doses of inhaled corticosteroids, as well as 334 (53%) with blood eosinophil counts of 300 cells/µL or higher in the previous 12 months.
“There really wasn’t any concerning safety signal for this agent,” Jackson said.
During AGILE, 265 (63%) patients in the previous depemokimab group and 129 (61%) in the previous placebo group experienced adverse events, with 15 (4%) in the previous depemokimab group and five (2%) in the previous placebo group related to study treatment.
On-treatment adverse events included infections and infestations (43%); respiratory, thoracic and mediastinal disorders (11%); and musculoskeletal and connective tissue disorders (11%).
Two of the adverse events in the previous depemokimab group and one in the previous placebo group led to permanent discontinuation of study treatment or withdrawal from the study.
Thirty-one (7%) of the adverse events in the previous depemokimab group and 16 (8%) in the previous placebo group were serious, but none of them were related to study treatment. There were no fatal serious adverse events or deaths.
Adverse events of special interest included single cases of pruritus, nausea and malaise in the previous placebo group; two cases of headache each in the previous depemokimab and placebo groups; and six local injection-site reactions in the previous depemokimab group.
Thirty-six of 396 patients in the previous depemokimab group and seven of 192 patients in the previous placebo group were positive for anti-drug antibodies, and three of 36 patients in the previous depemokimab group were positive for neutralizing antibodies.
Annualized rates of clinically significant on-treatment exacerbations over 52 weeks included 0.46 (95% CI, 0.38-0.56) for the previous depemokimab group and 0.48 (95% CI, 0.37-0.63) for the previous placebo group.
Overall, 450 (72%) of the patients in AGILE were exacerbation-free, and 604 (96%) did not experience any exacerbations that required hospitalization or an ED visit.
Exacerbations included 189 events for 114 patients while on treatment and seven events for seven patients after treatment in the previous depemokimab group, with 18 of the on-treatment events requiring hospitalization or an ED visit for 16 patients.
In the previous placebo group, exacerbations included 95 events for 62 patients while on treatment and two events for two patients after treatment, with nine of the on-treatment events requiring hospitalization or an ED visit for nine patients.
Based on these findings, the researchers concluded that patients tolerated long-term treatment with depemokimab with reductions in exacerbations as well as a safety profile and proportions of on-treatment adverse events consistent with previous studies.
“Two years of therapy with this ultra-long-acting biologic was both safe and had a good efficacy profile,” Jackson said.
GSK has submitted an application to the FDA and is now waiting for approval, he added.
“I think this will be another option for physicians and other providers to discuss with their patients,” Jackson said. “It’s a matter of thinking about shared decision-making with their patients to decide what’s the best choice for them.”
For more information:
Daniel J. Jackson, MD, can be reached at djj@medicine.wisc.edu.