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 and chronic rhinosinusitis with nasal polyps (CRSwNP). The efficacy of depemokimab over 52 weeks was demonstrated in the Phase III SWIFT-1/-2 studies in patients with type 2 (T2) asthma characterized by blood eosinophils. This integrated post hoc analysis of the SWIFT-1/-2 and AGILE open-label extension (OLE) studies assessed exacerbation rate reduction and improvement in patient-reported outcomes in patients with T2 asthma with comorbid CRSwNP. Methods In the SWIFT-1/-2 studies, patients aged ≥12 years were randomized 2:1 to receive depemokimab 100 mg or placebo subcutaneously every 26 weeks, up to 52 weeks. Patients who completed SWIFT-1/-2 were invited to join the single-arm AGILE OLE study, continuing with depemokimab (depemokimab/depemokimab) or switching from placebo to depemokimab (placebo/depemokimab) with follow-up for a total period of 104 Weeks. Outcomes included annualized exacerbation rate (AER) over 2 years and change from baseline (CFB) in SGRQ total and ACQ-5 scores (LS mean SE). Here we focus on the results of patients continuing with depemokimab. Results In SWIFT-1/-2 (N = 762), there was a 69% reduction in exacerbations versus placebo in the CRSwNP subgroup (AER: 0.51 depemokimab, n = 80 vs 1.61 placebo, n = 33) and a 51% reduction in those without CRSwNP (AER: 0.51 depemokimab, n = 421 vs 1.03 placebo, n = 227). SGRQ and ACQ-5 scores also showed greater improvements in the CRSwNP subgroup than in the overall population receiving depemokimab. 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). Of the 419 patients in the depemokimab/depemokimab group, 66 (15.8%) had comorbid CRSwNP at baseline. Across 2 years, the improvements observed in SWIFT-1/-2 were maintained in depemokimab/depemokimab patients with/without CRSwNP throughout the OLE. AER (95% CI) was 0.45 (0.31, 0.65) for patients with CRSwNP and 0.54 (0.46, 0.63) for patients without CRSwNP. Numerically greater improvements in SGRQ and ACQ-5 scores were maintained over the 2-year period regardless of CRSwNP status at baseline, with more pronounced improvements observed in those with CRSwNP (Figure). Conclusions Depemokimab showed sustained efficacy over the SWIFT/AGILE 2-year period in patients with T2 asthma, regardless of CRSwNP comorbidity status at baseline. An enhanced response was observed in patients with comorbid CRSwNP, with greater reductions in AER and improvements in SGRQ and ACQ-5 scores compared with those without CRSwNP. This abstract is funded by: GSK (SWIFT-1/-2: 206713/213744, NCT04719832/NCT04718103; AGILE: 212895/NCT05243680)
Pavord et al. (Fri,) studied this question.