Long-term safety and efficacy of twice-yearly depemokimab in type 2 asthma with an eosinophilic phenotype: 2-year integrated analysis of the phase 3a SWIFT-1 and SWIFT-2 studies and AGILE open-label extension

Depemokimab is the first ultra-long-acting biologic, with enhanced interleukin-5 binding affinity, high potency, and extended half-life, enabling twice-yearly dosing.

The double-blind, placebo-controlled, phase 3a SWIFT-1 and SWIFT-2 studies demonstrated depemokimab efficacy and safety over 52 weeks in patients with asthma with type 2 inflammation and an eosinophilic phenotype. Here, we present long-term safety and efficacy outcomes over the 52-week, phase 3a open-label extension (OLE) of SWIFT-1 and SWIFT-2 (AGILE) alongside an integrated post-hoc analysis of the 104-week SWIFT and AGILE period.

In SWIFT-1 and SWIFT-2, patients (aged ≥12 years) with asthma with type 2 inflammation, an eosinophilic phenotype (≥150 cells/μL at screening or ≥300 cells/μL during the previous 12 months), and a history of at least two exacerbations in the previous 12 months despite receiving medium-dose or high-dose inhaled corticosteroids were randomly assigned (2:1) to subcutaneous depemokimab 100 mg or placebo every 26 weeks in addition to standard of care for 52 weeks. Patients who completed SWIFT-1 or SWIFT-2 could join the single-arm, 52-week AGILE OLE study, conducted at 156 centres across 14 countries.

Patients continued depemokimab (depemokimab-depemokimab group) or switched to depemokimab from placebo (placebo-depemokimab group). The primary endpoints for the 52-week AGILE OLE period were the incidence of adverse events and serious adverse events, and immunogenicity as measured by the presence of anti-drug antibodies and neutralising antibodies.

Secondary efficacy outcomes, including exacerbation rate, St George's Respiratory Questionnaire (SGRQ) total score, Asthma Control Questionnaire-5 (ACQ-5) score, and pre-bronchodilator forced expiratory volume in 1 second (FEV 1 ), were also assessed. Additional post-hoc analyses were carried out to assess safety and efficacy over the 104-week integrated SWIFT and AGILE analysis period.

AGILE OLE is registered with ClinicalTrials.gov, NCT05243680. The SWIFT-1 and SWIFT-2 trials are registered with ClinicalTrials.gov, NCT04719832 and NCT04718103.

Between March 1, 2022, and May 19, 2025, 629 patients were included in the AGILE OLE study (419 patients in the depemokimab-depemokimab group and 210 patients in the placebo-depemokimab group). During the 52-week AGILE OLE period, adverse events occurred in 297 of 419 patients in the depemokimab-depemokimab group and 146 (70%) of 210 patients in the placebo-depemokimab group; serious adverse events were infrequent (37 [9%] of 419 in the depemokimab-depemokimab group and 19 [9%] of 210 in the placebo-depemokimab group), with no treatment-related or fatal serious adverse events reported.

In the depemokimab-depemokimab group, the reduced annualised exacerbation rate was sustained over 2 years (0·51 [95% CI 0·43-0·61] in the 52-week SWIFT-1 and SWIFT-2 period and 0·56 [0·47-0·66] in the AGILE OLE). Improvements in SGRQ total score, ACQ-5 score, and FEV 1 were maintained over 2 years.

In the placebo-depemokimab group, improvements in clinical outcomes were observed after the switch to depemokimab during the AGILE OLE.

Twice-yearly depemokimab was well tolerated and demonstrated sustained efficacy over the 2-year SWIFT and AGILE period, supporting its long-term therapeutic benefit and safety profile.