Late Breaking Abstract - Efficacy of high- and low-dose rilzabrutinib from a phase 2 study

<bold>Introduction:</bold> Rilzabrutinib is an investigational, oral, reversible, covalent Bruton’s tyrosine kinase inhibitor. <bold>Aim:</bold> Report on asthma control with low- and high-dose rilzabrutinib. <bold>Methods:</bold> This was a Phase 2, 12-week, double-blind, 2-staggered-cohort study in adults with poorly controlled moderate-to-severe asthma on ICS/LABA therapy (<ext-link>NCT05104892</ext-link>). 196 participants were randomized to rilzabrutinib 800mg (N=32) or placebo (N=32) and rilzabrutinib 1200mg (N=64) or placebo (N=68), added to medium-to-high-dose ICS/LABA, which was withdrawn starting at Week 4. The primary endpoint was the proportion of participants with a loss of asthma control (LOAC) event during treatment. Asthma control was assessed by the 5-item Asthma Control Questionnaire (ACQ-5). <bold>Results:</bold> Over 12 weeks, LOAC events occurred in 37.5% participants on rilzabrutinib 800mg vs 50% on placebo (OR:0.570; 95% CI:0.202-1.608), with a relative risk reduction (RRR) of 25%, and in 18.8% on rilzabrutinib 1200mg vs 29.4% on placebo (OR:0.584; 95% CI:0.253-1.349), with a RRR of 36.1%. Nominally significant improvements in ACQ-5 scores were observed as early as Week 2 with rilzabrutinib vs placebo and sustained up to Week 12 (LS mean difference vs placebo: rilzabrutinib 800mg: -0.59, p=0.0184; rilzabrutinib 1200mg: -0.54, p=0.0013) despite complete ICS/LABA withdrawal. ACQ-5 responders (improvements ≥0.5 from baseline) were higher with rilzabrutinib 800mg vs placebo (66.1% vs 35.9%; p=0.0100; rate difference [RD]=30%) and rilzabrutinib 1200mg vs placebo (59.8% vs 39.4%; p=0.0297; RD=20%) at Week 12. <bold>Conclusions:</bold> Rilzabrutinib was associated with reduced LOAC as well as significant and clinically meaningful improvement in asthma control over 12 weeks vs placebo.