mRNA 1345 an investigational respiratory syncytial virus vaccine has met primary endpoints in a phase III trial in older adults

Following review by an independent Data and Safety Monitoring Board (DSMB), the primary efficacy endpoints have been met, including vaccine efficacy (VE) of 83.7% (95.88% CI: 66.1%, 92.2%; p<0.0001) against rsv-associated lower respiratory tract disease (rsv-lrtd) as defined by two or more symptoms. based on these results, moderna intends to submit for regulatory approval in the first half of 2023.

"Today's results represent an important step forward in preventing lower respiratory disease due to RSV in adults 60 years of age and older. These data are encouraging, and represent the second demonstration of positive phase III trial results from our mRNA infectious disease vaccine platform after, Spikevax, our COVID-19 vaccine. We look forward to publishing the full data set and sharing the results at an upcoming infectious disease medical conference," said Stéphane Bancel, Moderna's Chief Executive Officer. "Respiratory diseases are a major public health priority given they have a significant health impact and are a leading cause of hospitalization. For these reasons, in addition to our mRNA 1345 RSV vaccine candidate, we are committed to developing a portfolio of respiratory mRNA vaccines to target the most significant viruses causing respiratory disease, including COVID-19, influenza, and human metapneumovirus."

The ConquerRSV trial is a randomized, double-blind, placebo-controlled study of approximately 37,000 adults 60 years or older in 22 countries, including the US (NCT05127434). The primary efficacy endpoints were based on two definitions of RSV-LRTD defined as either two or more symptoms, or three or more symptoms of disease. The interim analysis was based on 64 cases of RSV-LRTD with two or more symptoms, of which 55 occurred in the placebo group and 9 occurred in the mRNA 1345 group, and 20 cases of RSV-LRTD with three or more symptoms, of which 17 cases were observed in the placebo group compared with three cases observed 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.

A concurrent review of available safety data was also conducted by the DSMB. mRNA 1345 was well tolerated with no safety concerns identified. Safety and tolerability will continue to be followed in this ongoing study. To date most solicited adverse reactions were mild or moderate and the most commonly reported solicited adverse reactions in the mRNAb 1345 group were injection site pain, fatigue, headache, myalgia, and arthralgia. The overall rate of severe (Grade 3 or greater) solicited systemic adverse reactions was 4.0% for mRNA 1345 and 2.8% for placebo. The overall rate of Grade 3 or greater solicited local adverse reactions was 3.2% for mRNA 1345 and 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.