Efficacy and safety of CM310 in moderate to severe asthma: a multicenter, randomized, double-blind, placebo-controlled phase 2 study

Background: CM310 is a humanised anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits IL-4 and IL-13 signaling which contribute to the pathophysiology of asthma. This study (NCT05186909) aimed to evaluate the efficacy and safety of CM310 in patients (pts) with moderate to severe asthma. Methods: In this phase 2 study, pts were randomly assigned (1:1:1) to receive CM310 300 mg, 150 mg, or placebo administered subcutaneously every 2 weeks for 24 weeks. The primary endpoint was change from baseline to week 12 in prebronchodilator FEV1. Results: 52 pts were enrolled in CM310 300 mg (n=18), 150 mg (n=16), or placebo group (n=18) with baseline mean prebronchodilator FEV1 of 1.50, 1.43 and 1.33 L respectively. Compared with placebo, change from baseline in prebronchodilator FEV1 at week 12 was greater with CM310 300 mg and 150 mg (LS mean difference, 99.0 [95% CI -243.4-441.4] mL and 342.0 [95% CI 75.0-676.3] mL). CM310 300 mg reduced annualized asthma exacerbation rate over 24 weeks by 53.9% (RR=0.46) and by 84.7% with 150 mg (RR=0.15) vs. placebo. Significant improvement in ACQ-5 score with CM310 300 mg and 150 mg vs. placebo by 0.86 and 0.60 points was seen early at week 2, and was maintained till week 24. The incidence of treatment emergent adverse events (TEAEs) was 100%, 93.8%, 83.3% for CM310 300 mg, 150 mg, placebo group, and most were grade 1-2 (≥ grade 3 TEAEs: 5.6% vs. 12.5% vs. 16.7%). Conclusion: CM310 was well tolerated and resulted in clinically meaningful improvement in pulmonary function and quality of life, reductions in asthma exacerbations in the pts with moderate to severe asthma.