Respiratory syncytial virus (rsv) vaccine mrna-1345 by moderna has reached primary efficacy endpoints in phase 3 trial in older adults
- mRNA-1345 demonstrated vaccine efficacy of 83.7% against RSV lower respiratory tract disease, defined by 2 or more symptoms in older adults
- mRNA-1345 was generally well-tolerated, and the DSMB found no safety issues
- Based on these findings, Moderna plans to request regulatory approval for mRNA-1345
mRNA-1345, an investigational mRNA vaccine that targets respiratory syncytial virus (RSV) in older persons, was studied in the ConquerRSV Phase 3 pivotal effectiveness study by Moderna, a biotechnology company that has pioneered messenger RNA (mRNA) medicines and vaccines. The major efficacy endpoints, including vaccine effectiveness (VE) of 83.7% (95.88% CI: 66.1%, 92.2%; p0.0001) against RSV-associated lower respiratory tract illness (RSV-LRTD) as characterised by two or more symptoms, have been fulfilled following review by an independent Data and Safety Monitoring Board (DSMB). Moderna plans to apply for regulatory permission in the first half of 2023 in light of these findings.
A randomised, double-blind, placebo-controlled trial called ConquerRSV involved over 37,000 persons aged 60 or older from 22 different countries, including the US (NCT05127434). The two definitions of RSV-LRTD—two or more symptoms or three or more symptoms of the disease—were used to determine the primary effectiveness endpoints. The interim analysis was based on 20 cases of RSV-LRTD with three or more symptoms, of which 17 cases were observed in the placebo group compared to three cases observed in the mRNA-1345 group. The interim analysis also included 64 cases of RSV-LRTD with two or more symptoms, of which 55 cases occurred in the placebo group and 9 cases occurred in the mRNA-1345 group. The other primary efficacy endpoint against RSV-LRTD defined by three or more symptoms was also met, with a VE of 82.4% (96.36% CI: 34.8%, 95.3%; p=0.0078). The trial is ongoing, and additional efficacy analyses are planned as cases accrue, including for severe RSV.
The DSMB also reviewed the safety data that was accessible concurrently. No safety issues were found with mRNA-1345, which was well tolerated. This continuing study will continue to monitor safety and tolerability. Injection site pain, weariness, headache, myalgia, and arthralgia were the most frequently reported solicited adverse events in the mRNA-1345 group, and most solicited adverse reactions to date have been mild or moderate. mRNA-1345 had a 4.0% overall rate of severe (Grade 3 or higher) provoked systemic adverse events compared to a 2.8% rate for placebo. The rate of requested local adverse events of Grade 3 or higher overall was 3.2% with mRNA-1345 versus 1.7% for placebo. The study is ongoing, and an updated analysis of safety and tolerability will be provided at the time of regulatory submission.
Moderna will submit the data for peer-reviewed publication and present it at an upcoming scientific meeting.