B32-04 Efficacy of Rilzabrutinib on Asthma Quality of Life: Pooled Results From a Double-blind Placebo-controlled Phase 2 Study

Rationale Asthma is a common chronic inflammatory disease of the airways. Despite available therapies, there are individuals whose asthma remains uncontrolled, which can negatively affect health-related quality of life (HRQoL). Rilzabrutinib (SAR444671), an oral, selective, reversible, covalent Bruton’s tyrosine kinase inhibitor, was evaluated in adults with poorly controlled moderate-to-severe asthma despite treatment with inhaled corticosteroid (ICS)/long-acting β2 adrenergic agonist (LABA) therapy. Here we report the effect of pooled rilzabrutinib 800 mg and rilzabrutinib 1200 mg daily on HRQoL over 12 weeks. Methods This was a phase 2, double-blind, two-staggered-cohort study evaluating the efficacy and safety of rilzabrutinib (NCT05104892). A total of 196 adult participants with poorly controlled moderate-to-severe asthma on medium-to-high dose ICS/LABA therapy were randomized to receive rilzabrutinib 800 mg (n = 32) or placebo (n = 32) and rilzabrutinib 1200 mg (n = 64) or placebo (n = 68) for 12 weeks. ICS/LABA therapy was withdrawn from week 4 to week 9. The treatment effect of rilzabrutinib versus placebo on HRQoL was evaluated using the Asthma Quality of Life Questionnaire with Standardized Activities (AQLQ[S]). Changes from baseline in global and domain scores (range: 1 = severe impairment to 7 = no impairment) were assessed through week 12. The proportion of participants achieving a clinically meaningful improvement (≥0.5-point increase in AQLQ[S] global score) was analyzed at week 12. Results At baseline, mean AQLQ(S) global scores were 4.94 (standard deviation [SD]: 0.84) and 4.67 (SD: 0.91) for pooled rilzabrutinib (n = 96) and placebo (n = 100), respectively. Improvement in AQLQ(S) global score for rilzabrutinib vs placebo was observed as early as week 4 (least squares [LS] mean difference from baseline: 0.36; 95% confidence interval [CI]: 0.11‒0.61; p = 0.0045), and sustained up to week 12 despite ICS/LABA withdrawal (LS mean difference: 0.44; 95% CI: 0.19‒0.69; p = 0.0006). Improvements in AQLQ(S) domain scores were observed by week 4 with rilzabrutinib vs placebo and sustained through week 12 (LS mean differences: symptoms, 0.43, p = 0.0013; activity limitation, 0.47, p = 0.0002; emotional function, 0.44, p = 0.0088; environmental stimuli, 0.41, p = 0.0217). At week 12, 51.4% and 37.7% of participants achieved a clinically meaningful response (≥0.5 points on AQLQ[S]) with pooled rilzabrutinib vs placebo (p = 0.0057), respectively. Conclusions Rilzabrutinib demonstrated rapid and clinically meaningful improvements in asthma-related QoL (AQLQ[S]) vs placebo in participants with poorly controlled moderate-to-severe asthma over 12 weeks of treatment. Improvements were maintained despite withdrawal of ICS/LABA background therapy beginning at week 4.