The RSV candidate represents Moderna’s most advanced candidate using its mRNA infectious disease platform after its commercial COVID-19 Spikevax vaccine.
Although RSV vaccine development dates back to the 1960s, there are currently no approved vaccines against RSV. Moderna’s Phase 3 success, however, brings its candidate up close behind Pfizer and GSK’s candidates (which have both filed a Biologics License Application with the FDA with decisions expected in May).
'Important step forward'
RSV is a highly contagious seasonal respiratory virus and a leading cause of lower respiratory tract infections and pneumonia, causing a particularly large burden of disease in infants and older adults (each year in the US, approximately 60,000-120,000 older adults are hospitalized, and 6,000-10,000 of them die due to RSV infection).
Moderna's RSV vaccine, mRNA-1345, consists of a single mRNA sequence encoding for a stabilized prefusion F glycoprotein: using the same lipid nanoparticles (LNPs) as in the Moderna COVID-19 vaccines.
The primary efficacy endpoints of the trial (NCT05127434) 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).
Moderna’s ConquerRSV Phase 3 trial is assessing mRNA-1345 in around 37,000 older adults (aged 60+) in 22 countries, including the US.
With a 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, the primary endpoints of the trial have now been met.
The vaccine was ‘generally well-tolerated, with no safety concerns identified by the independent Data and Safety Monitoring Board’.
The trial is ongoing, and additional efficacy analyses are planned as cases accrue, including for severe RSV. Moderna is aiming to submit the vaccine for regulatory approval 'in the first half of 2023'.
"These results represent an important step forward in preventing lower respiratory disease due to RSV in adults 60 years of age and older," said Stéphane Bancel, CEO, Moderna.
"These data are encouraging, and represent the second demonstration of positive phase 3 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.
"Respiratory diseases are a major public health priority given they have a significant health impact and are a leading cause of hospitalization."
Moderna: mRNA-1345
- In data published this week, Moderna reported vaccine efficacy of 83.7% against RSV lower respiratory tract illness defined by 2 or more symptoms in older adults. The vaccine was ‘generally well-tolerated with no safety concerns’.
- mRNA-1345 is an investigational RSV vaccine that consists of a single mRNA sequence encoding for a stabilized prefusion F glycoprotein. The vaccine uses the same lipid nanoparticles (LNPs) as in the Moderna COVID-19 vaccines. The F glycoprotein is on the surface of the virus and is required for infection by helping the virus to enter host cells. It exists in two states, prefusion and postfusion. The prefusion conformation is a significant target of potent neutralizing antibodies and is highly conserved across both RSV-A and RSV-B subtypes.
- Submission for regulatory approval is expected in the first half of 2023
Pfizer: PF-06928316 / RSVpreF
- In data published in August, Pfizer reported vaccine efficacy of 85.7% in participants aged 60+ with more severe disease primary endpoint of lower respiratory tract illness (LRTI-RSV) defined by analysis of three or more RSV-associated symptoms. The vaccine was ‘well-tolerated with no safety concerns’.
- The bivalent vaccine candidate is composed of two preF proteins selected to optimize protection against RSV A and B strains.
- In the US, the vaccine has a PDUFA goal date of May, 2023.
GSK: RSVPreF3 OA
- In data published in October, GSK reported overall vaccine efficacy of 82.6% for its vaccine in adults aged 60+, with consistent efficacy against RSV A and B strains. The vaccine has a ‘favorable safety profile’.
- This candidate contains a recombinant subunit prefusion RSV F glycoprotein antigen (RSVPreF3) combined with GSK’s proprietary AS01E adjuvant.
- In the US, the vaccine has a PDUFA goal date of May, 2023.
Moderna's RSV Clinical Trials
The Phase 3 ConquerRSV trial is one of five ongoing RSV trials, including pediatric and combination clinical trials.
A fully enrolled Phase 1 trial is assessing the same vaccine in pediatric populations. Moderna also plans to take a combined pediatric RSV + hMPV vaccine mRNA-1365 into a Phase 1 trial (Like RSV, hMPV is a major cause of lower respiratory tract infection in the pediatric population and a common cause of morbidity and mortality in immunocompromised patients and older adults).
Meanwhile, candidates for adults include combinations against RSV, COVID-19, influenza, and human metapneumovirus (hMPV). Moderna recently started a Phase 1 study of mRNA-1230 targeting SARS-CoV-2, influenza, and RSV, and mRNA-1045 targeting influenza and RSV. In an ongoing Phase 3 trial, Moderna is evaluating the coadministration of mRNA-1345 and a licensed influenza vaccine, and coadministration of mRNA-1345 with mRNA-1273.214.