SHR-1703, a novel long-acting anti-interleukin-5 monoclonal antibody, in asthma patients: A randomized, double-blind, placebo-controlled phase 1 study.

AIM: Interleukin 5 is an important target for the treatment of eosinophil-associated diseases including eosinophilic asthma. SHR-1703 is an innovative humanized anti-interleukin-5 monoclonal antibody designed to improve asthma control. This study aimed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of SHR-1703 in asthma patients.

METHODS

In the single ascending dose study, eligible patients were randomized to receive SHR-1703 (400 or 600 mg) or placebo and followed up to Day 281. Primary endpoints were safety and tolerability.

RESULTS

Most treatment-emergent adverse events (TEAEs) were mild or moderate. The incidence of TEAEs was comparable between the SHR-1703 and placebo groups. The median (range) Tmax was 13.9 (7.0-14.1) and 10.3 (10.0-14.0) days for SHR-1703 400 and 600 mg, respectively. SHR-1703 at 400 and 600 mg has an extended mean (standard deviation) half-life of 75.1 (11.1) and 72.6 (12.7) days. Meanwhile, SHR-1703 markedly and rapidly reduced peripheral blood eosinophils by over 50% in 1 day. The largest mean (standard deviation) decline of eosinophils from baseline reached 87.7 (5.8)% for 400 mg and 91.1 (4.7)% for 600 mg, with the effect sustained over 100 days. The eosinophil levels remained below the baseline up to the end of follow-up.

CONCLUSION

SHR-1703 was well-tolerated and showed promising efficacy in eosinophilic asthma patients.