Abstract Rationale High-dose inhaled corticosteroids (ICS) are associated with increased side effects and earlier initiation of biologics is desirable. 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 was demonstrated over 52 weeks in patients with type 2 asthma in the Phase III SWIFT-1/-2 studies. This integrated post hoc analysis of the SWIFT-1/-2 and AGILE open-label extension (OLE) studies evaluated the long-term efficacy of depemokimab by baseline ICS dose in patients with type 2 asthma. Methods In SWIFT-1/-2, patients aged ≥12 years on medium- or high-dose ICS were randomized 2:1 to subcutaneous depemokimab 100 mg or placebo every 26 weeks, up to 52 weeks. After completing SWIFT-1/-2, patients were invited to join the single-arm AGILE OLE study, continuing depemokimab (depemokimab/depemokimab) or switching from placebo to depemokimab (placebo/depemokimab) with follow-up for up to 104 weeks. Outcomes included annualized exacerbation rate (AER) and LS mean (SE) change from baseline (CFB) in SGRQ total score and ACQ-5 score by baseline ICS use (medium/high) over 2 years. Here we focus on the results of patients continuing with depemokimab. Results In SWIFT-1/-2 (N = 762), depemokimab reduced exacerbations by 54% versus placebo (rate ratio 95% CI: 0.46 0.36, 0.59); in the depemokimab group, AER (95% CI) over 52 weeks was 0.36 (0.27, 0.48) for medium-dose ICS subgroup and 0.65 (0.53, 0.79) for high-dose ICS subgroup. Improvements in SGRQ and ACQ-5 scores were observed with depemokimab regardless of baseline ICS dose: LS mean (SE) CFB at Week 52 with depemokimab in the medium- and high-dose ICS subgroups, respectively, was -14.38 1.19 and -13.60 1.01 for SGRQ and -0.89 0.07 and -0.76 0.06 for ACQ-5. 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). At baseline, 172 and 247 patients in the depemokimab/depemokimab group were on medium- and high-dose ICS, respectively. In the depemokimab/depemokimab group, AER was maintained over 2 years in both the medium- (0.41 0.32, 0.52) and high-dose (0.62 0.52, 0.75) ICS subgroups. CFB in SGRQ and ACQ-5 scores were sustained throughout the 2-year period for both medium- and high-dose ICS subgroups (Figure). Conclusions Twice-yearly depemokimab demonstrated sustained efficacy over 2 years, irrespective of baseline ICS dose. These results support the long-term efficacy of depemokimab in asthma and its potential initiation prior to high-dose ICS escalation. This abstract is funded by: GSK (SWIFT-1/-2: 206713/213744, NCT04719832/NCT04718103; AGILE: 212895/NCT05243680)
Panettieri et al. (Fri,) studied this question.
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