Abstract Rationale Depemokimab is the first ultra-long-acting biologic, with enhanced interleukin-5 binding affinity, high potency, and extended half-life, enabling twice-yearly dosing in asthma. Depemokimab efficacy has been demonstrated in Phase III SWIFT-1/-2 studies in patients with type 2 (T2) asthma. Here we assess depemokimab long-term efficacy in an integrated post hoc analysis of the SWIFT-1/-2 and AGILE open-label extension (OLE) studies. Methods Eligible adults with T2 asthma characterized by blood eosinophil counts (BEC) were randomized 2:1 to receive subcutaneous depemokimab 100 mg or placebo every 26 weeks for 52 weeks in SWIFT-1/-2. Patients who completed SWIFT-1/-2 were invited to join the single-arm AGILE OLE study, continuing with depemokimab (depemokimab/depemokimab group) or switching from placebo to depemokimab (placebo/depemokimab group) with follow-up for a total period of 104 weeks. Efficacy endpoints included annualized exacerbation rate (AER), least squares mean (SE) change from baseline (CFB) at the start of SWIFT-1/-2 in St George’s Respiratory Questionnaire (SGRQ) total score, Asthma Control Questionnaire (ACQ)-5 score over 104 weeks, and BEC over time. Results In SWIFT-1/-2 (N = 762), AER (95% CI) over 52 weeks was 0.51 (0.43, 0.60) in the depemokimab group (n = 502), representing a 54% reduction versus placebo (AER 95% CI: 1.11 0.92, 1.33; n = 260). Overall, 641 (84%) patients entered AGILE; 629 received ≥1 depemokimab dose and were included in the integrated analysis (n = 419, depemokimab/depemokimab; n = 210, placebo/depemokimab). AER reduction was maintained over the full 2-year SWIFT/AGILE period in the depemokimab/depemokimab group (0.52 0.45, 0.60). CFB in SGRQ total score with depemokimab at Week 52 of SWIFT-1/-2 was −13.92 (0.76), with maintenance of the response in the depemokimab/depemokimab group over the 2-year SWIFT/AGILE period (CFB at Week 104: −16.29 0.85). Similarly, CFB in ACQ-5 score with depemokimab at Week 52 in SWIFT-1/-2 was −0.81 (0.05); this reduction was sustained across the 2-year period (CFB at Week 104: −0.89 0.05). Suppression of T2 inflammation, assessed by BEC, was consistent throughout the 2-year period in the depemokimab/depemokimab group (ratio to baseline SE logs at Week 104: 0.174 0.04). Rapid and clinically relevant improvements in clinical outcomes were also observed during Year 2 in patients who switched from placebo to depemokimab at Week 52. These improvements were sustained through to end of treatment. Conclusions Depemokimab showed sustained suppression of inflammation and clinically meaningful efficacy which was maintained over a 2-year period in patients with T2 asthma. These results support the long-term efficacy of depemokimab in asthma. This abstract is funded by: GSK (SWIFT-1/-2: 206713/213744, NCT04719832/NCT04718103; AGILE: 212895/NCT05243680).
Pavord et al. (Fri,) studied this question.