Moderna’s Investigational RSV Vaccine: Preparing for Potential Launch This Year

Last week, Moderna had its fifth annual Vaccines Day. During this day, the company provides updates on its vaccine pipeline. One of the company’s vaccines, its investigational RSV, mRNA-1345, has its PDUFA date in 5 weeks.¹ This vaccine has shown in earlier data that it demonstrated an efficacy of 83.7% against RSV-associated lower respiratory tract disease (RSV-LRTD) as defined by two or more symptoms.²

"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 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," Moderna CEO Stéphane Bancel, said in a statement at the time of the data’s release.³

What the Data Demonstrated
The company conducts its phase 3 ConquerRSV trial, which is a randomized, double-blind, placebo-controlled study of approximately 37,000 adults who are 60 years or older across 22 countries. The investigators based their primary efficacy endpoints around 2 definitions of RSV-LRTD defined as either two or more symptoms, or three or more symptoms of disease.²

The interim analysis was based on 64 cases of RSV-LRTD with 2 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.²

A subsequent analysis from the ConquerRSV study with a longer median follow-up duration of 8.6 months (versus 3.7 months in the primary analysis), with a range of 15 days to 530 days, and including subjects from the Northern and Southern Hemispheres was recently presented at the RSVVW'24 conference. In this supplemental analysis, mRNA-1345 maintained durable efficacy, with sustained VE of 63.3% (95.88% CI: 48.7%, 73.7%) against RSV-LRTD including two or more symptoms. VE was 74.6% (95% CI: 50.7%, 86.9%) against RSV-LRTD with ≥2 symptoms, including shortness of breath and 63.0% (95% CI: 37.3%, 78.2%) against RSV-LRTD including three of more symptoms.⁴

In terms of safety, a review of available safety data was also conducted by the DSMB. The mRNA-1345 vaccine was well tolerated with no safety concerns identified, according to the investigators. 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 mRNA-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.²

The RSV Vaccine’s Makeup
mRNA-1345 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.

References

1. 5 FDA decisions to watch in the second quarter. Biopharmdive. April 1, 2024. Accessed April 4, 2024. https://www.biopharmadive.com/news/5-fda-approval-decisions-watch-second-quarter-2024/711831/

2. Parkinson J. Moderna RSV Vaccine Granted FDA Breakthrough Therapy Status. Contagion. January 31, 2023. Accessed April 4, 2024
https://www.contagionlive.com/view/moderna-rsv-vaccine-granted-fda-breakthrough-therapy-status

3. Moderna Announces mRNA-1345, an Investigational Respiratory Syncytial Virus (RSV) Vaccine, Has Met Primary Efficacy Endpoints in Phase 3 Trial in Older Adults. Moderna Press release. January 17, 2023. Accessed April 4, 2024.
https://investors.modernatx.com/news/news-details/2023/Moderna-Announces-mRNA-1345-an-Investigational-Respiratory-Syncytial-Virus-RSV-Vaccine-Has-Met-Primary-Efficacy-Endpoints-in-Phase-3-Trial-in-Older-Adults/default.aspx

4. Moderna Advances Multiple Vaccine Programs to Late-Stage Clinical Trials. Moderna Press release. March 27, 2023. Accessed April 4, 2024. https://investors.modernatx.com/news/news-details/2024/Moderna-Advances-Multiple-Vaccine-Programs-to-Late-Stage-Clinical-Trials/default.aspx