A phase I study to evaluate safety, pharmacokinetics, and pharmacodynamics of respiratory syncytial virus neutralizing monoclonal antibody MK‐1654 in healthy Japanese adults

Abstract

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among all infants worldwide and remains a significant cause of morbidity and mortality. To address this unmet medical need, MK-1654, a half-life extended RSV neutralizing monoclonal antibody, is in clinical development for the prevention of RSV disease in infants. This was a phase I, randomized, placebocontrolled, single-site, double-blind trial of MK-1654 in 44 healthy Japanese adults. The safety, tolerability, pharmacokinetics, antidrug antibodies (ADAs), and serum neutralizing antibody (SNA) titers against RSV were evaluated for 1 year after a single intramuscular (i.m.) or intravenous (i.v.) dose of MK-1654 or placebo in five groups (100 mg i.m., 300 mg i.m., 300 mg i.v., 1000 mg i.v., or placebo). MK-1654 was generally well-tolerated in Japanese adults. There were no serious drug-related adverse events (AEs) reported in any MK-1654 recipient and no discontinuations due to any AEs in the study. The half-life of MK-1654 ranged from 76 to 91 days across dosing groups. Estimated bioavailability was 86% for 100 mg i.m. and 77% for 300 mg i.m. One participant out of 33 (3.0%) developed detectable ADA with no apparent associated AEs. The RSV SNA titers increased in a dose-dependent manner among participants who received MK-1654. These data support the development of MK-1654 for use in Japanese infants. How to cite this article: Orito Y, Otani N, Matsumoto Y, et al. A phase I study to evaluate safety, pharmacokinetics, and pharmacodynamics of respiratory syncytial virus neutralizing monoclonal antibody MK-1654 in healthy Japanese adults.

Clinical research on RSV prevention in children and pregnant women: progress and perspectives

“…Orito et al. ( 47 ) proved that the bioavailability of MK-1654 in healthy adults was 86% and 77% for the 100 mg i.m. and 300 mg i.m.…”

“…There was no significant difference in safety events between the MK1654 and placebo groups. Orito et al (47) proved that the bioavailability of MK-1654 in healthy adults was 86% and 77% for the 100 mg i.m. and 300 mg i.m.…”

The road to approved vaccines for respiratory syncytial virus

“…It recognizes a quaternary epitope, preferentially binding preF over postF and demonstrating high in vivo potency against subtype A and B RSV 78 . Data are available from testing in healthy adults, and modeling studies predict high levels of protection from LRTI through 150 days at a dose of ≥ 75 mg in infants [79][80][81] . A phase 2b/3 efficacy study in healthy pre-and full-term infants (NCT04767373) is estimated to be completed in 2024, and a phase 3 comparison to palivizumab in high-risk infants (NCT04938830) in 2026.…”

We are all on the same team

“…152). An in vitro study showed high potency against RSV-A and RSV-B clinical isolates and low threshold to resistance, but efficacy is largely unknown with only phase I adult data published to date 153,154 . A phase Ib/IIa study showed 80.6% efficacy against medically attended RSV LRTI (unpublished data; see ref.…”