B94-09 Astegolimab Improves HRQoL in Patients With COPD: Evaluating SGRQ-C Response in ALIENTO and ARNASA

Rationale Astegolimab, an anti-ST2 (IL-33 receptor) monoclonal antibody, was assessed for efficacy and safety in patients with chronic obstructive pulmonary disease (COPD) in the Phase IIb ALIENTO (NCT05037929) and Phase III ARNASA (NCT05595642) trials (results presented elsewhere). Here we report the impact of astegolimab on health-related quality of life (HRQoL), as measured by the St. George’s Respiratory Questionnaire (SGRQ-C) in ALIENTO and ARNASA. Methods Patients with COPD (current/former smokers, with history of ≥ 2 moderate or severe exacerbations within a previous 12-month period, regardless of baseline blood eosinophil count or chronic bronchitis diagnoses) were randomized 1:1:1 to receive astegolimab 476 mg subcutaneously every 2 weeks (Q2W), every 4 weeks (Q4W), or placebo for 52 weeks. Prespecified endpoints included change from baseline in SGRQ-C total score at Week 52, and proportion of responders, i.e. patients achieving total score improvement of ≥ 4 points, the minimal clinically important difference, at Weeks 12, 24, and 52 for the individual studies and pooled results. A prespecified post-hoc analysis of SGRQ-C subdomain scores (symptoms, activity, and impacts) was performed. Results 1301 and 1375 patients were included in the modified intent-to-treat population in ALIENTO and ARNASA, respectively. The adjusted mean change from baseline in SGRQ-C total score numerically favored astegolimab Q2W vs placebo at Week 52 (ALIENTO: -1.87 [p=0.086], ARNASA: -0.77 [p=0.537], pooled: -1.307 [p=0.120]). Similar results were observed for Q4W. Improvements in SGRQ-C were observed as early as Week 12 and maintained throughout the treatment period for both studies (Figures A and B). Astegolimab Q2W increased the proportion of participants with ≥4-point decrease from baseline in SGRQ-C total score vs placebo (ALIENTO: OR 1.20 [95% CI 0.90, 1.60, p=0.212], ARNASA: OR 1.49 [95% CI 1.14, 1.96, p=0.004], pooled: OR 1.35 [95% CI 1.11, 1.64, p=0.003]). Similar improvement was observed in Q4W. This SGRQ responder improvement for astegolimab Q2W versus placebo was consistent regardless of baseline blood eosinophil count, smoking status, or chronic bronchitis status. Numerical improvements from baseline for astegolimab Q2W versus placebo were observed in all three SGRQ subdomains, with greatest impact in the symptom subdomain. Conclusions Astegolimab demonstrated positive impacts in SGRQ-C responders in the ALIENTO, ARNASA and pooled analyses. Changes in SGRQ-C total scores were observed as early as 12 weeks, with the greatest numerical impact in the symptom subdomain score analysis. This abstract is funded by: These studies were sponsored by F. Hoffman-La Roche Ltd/Genentech, a member of the Roche Group.