mRESVIA® (mRNA-1345) RSV Vaccine Clinical Trials, Dosage, Efficacy, Side Effects
Moderna Inc.'s mRESVIA® (mRNA-1345) Respiratory Syncytial Virus (RSV) messenger RNA (mRNA) vaccine candidate encodes for a prefusion F glycoprotein and uses lipid nanoparticles (LNPs), eliciting a superior neutralizing antibody response. The prefusion conformation is a significant target of potent neutralizing antibodies, and the protein sequences are primarily similar across both RSV-A and RSV-B subtypes. This mRNA is entirely made in a laboratory and instructs your body to create small pieces of proteins. In addition, this RSV vaccine contains the mRNA code for the RSV glycoprotein F. It does not cause RSV infection but helps the body's immune system recognize and protect itself if it encounters the RSV virus. Furthermore, you cannot become infected with RSV by receiving Moderna's investigational vaccine.
Moderna initiated a rolling submission of a Biologics License Application (STN: 125796) to the U.S. Food and Drug Administration (FDA) for mRNA-1345. On May 31, 2024, the FDA approved mRESVIA (mRNA-1345). The FDA previously granted Fast Track and Breakthrough Designation designations for mRNA-1345 in adults older than 60.
Massachusetts-based Moderna's mRNA platform builds on continuous advances in basic and applied mRNA science, delivery technology, and manufacturing and has allowed the development of therapeutics and vaccines. To learn more, visit www.modernatx.com.
mRESVIA (mRNA-1345) Vaccine Availability
mRNA-1345 was approved by the U.S. FDA (STN: 125796) in May 2024. And mRNA-1345 was recommended by the CDC's Advisory Committee on Immunization Practices on June 26, 2024. Moderna expects to have mRESVIA available in the U.S. by the 2024/2025 RSV season. On June 28, 2024, the European Medicines Agency's (EMA) vaccine committee recommended mRSVIA for authorization in Europe.
On September 13, 2023, the Company stated regulatory applications were submitted in Switzerland (Swissmedic), Australia (TGA), Canada (Health Canada), and the United Kingdom (MHRA). The Company plans to launch its RSV vaccine in Australia and Germany in 2024 and other markets in 2025.
mRESVIA (mRNA-1345) Vaccine Indication
The mRNA-1345 RSV vaccine candidate is indicated to prevent illness from RSV, a leading cause of respiratory disease in young children and older adults (65+). RSV is the most common cause of bronchiolitis (inflammation of the small airways in the lung) and pneumonia (infection of the lungs) in children younger than one year. According to the U.S. CDC, RSV leads each year, on average, to approximately 58,000 hospitalizations among children younger than five years old, 177,000 hospitalizations among adults 65 years and older, and 14,000 deaths among adults 65 years and older.
mRESVIA (mRNA-1345) Vaccine Dosage
The data from a Phase 1 study in older adults ages 65-79 showed that a single mRNA-1345 vaccination of 50 µg, 100 µg, or 200 µg boosted neutralizing antibody titers against RSV-A by approximately 14-fold and against RSV-B by about 10-fold. The U.S. FDA updated the data.
mRESVIA (mRNA-1345) Vaccine Efficacy
Moderna's presentation to the U.S. Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) on June 26, 2024, disclosed that mRESVIA (mRNA-1345) showed about 81% efficacy after 3.7 months but only 50% efficacy in preventing the illness after 18 months. On October 25, 2023, the ACIP confirmed the Work Group was reviewing the safety and efficacy of Moderna's mRNA-1345 for use in adults 60 and older. On February 29, 2024, the ACIP committee reviewed the results of the Pivotal Phase 2/3 clinical trial (36,557 Participants Enrolled in 22 Countries). The mRNA-1345 vaccine was generally well tolerated in >19,500 individuals with no safety concerns. The ACIP reviewed a Phase 1 trial: Concomitant administration with influenza and COVID-19 vaccines.
mRESVIA (mRNA-1345) Vaccine Safety
The U.S. FDA published an updated Package Insert. The NEJM published an ORIGINAL ARTICLE in December 2023 - Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults. A single dose of the mRNA-1345 vaccine resulted in no evident safety concerns. It led to a lower incidence of RSV-associated lower respiratory tract disease and RSV-associated acute respiratory disease than placebo among adults 60 years of age or older. (Funded by Moderna; ConquerRSV ClinicalTrials.gov number, NCT05127434) Moderna announced in July 2023 that the vaccine candidate was well tolerated and had a favorable safety profile. 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. Moderna presented: Safety and Efficacy of mRNA-1345, an mRNA-based Vaccine Against RSV, in Adults 60 Years and Older on February 23, 2023, at the 7th ReSViNET Conference. Conclusion: mRNA-1345 was well tolerated and had an acceptable safety profile; solicited adverse reactions were mostly grade 1 or grade 2 in severity.
mRESVIA (mRNA-1345) Vaccine News
June 28, 2024 - Moderna's chief Executive Officer said in a press release, "mRESVIA protects older adults from the severe outcomes of RSV infection, and it is the only RSV vaccine available in a pre-filled syringe designed to maximize ease of administration, saving vaccinators' time and reducing the risk of administrative errors."
May 31, 2024 - Stéphane Bancel, Chief EStéphane Bancel, Chief Executive Officer of Moderna. "mRESVIA safeguards older adults against severe RSV outcomes and is uniquely offered in a pre-filled syringe to enhance ease of administration, which can save healthcare professionals time and reduce administrative errors.
February 29, 2024 - Moderna Inc. presented an RSV vaccine update to the U.S. CDC's ACIP committee.
February 7, 2024 - Moderna Inc. posted: Respiratory Syncytial Virus (RSV): What You Need to Know.
July 5, 2023 - "We are proud to announce these filings for the use of our RSV vaccine candidate, mRNA-1345, in the European Union, Switzerland, Australia, and the U.S. RSV is a major cause of lower respiratory tract infections in older adults and significantly burden to health systems through hospitalizations and emergency care admissions," said Stéphane Bancel, Chief Executive Officer of Moderna, in a press release.
March 24, 2022 - Moderna confirmed that a Phase 1 RSV trial (mRNA-1345) is ongoing, evaluating tolerability, reactogenicity, and immunogenicity in children, younger adults, older adults, and women of childbearing age. In an interim analysis, mRNA-1345 boosted RSV-neutralizing antibodies and was well-tolerated at all doses in younger and older adults.
August 3, 2021 - Moderna, Inc. announced that the U.S. FDA had granted Fast Track designation for mRNA-1345, its investigational single-dose mRNA vaccine against RSV in adults older than 60.
April 14, 2021 - Moderna shared the first interim analysis of the Phase 1 study after 1-month post-vaccination of younger adults (18-49).
mRESVIA (mRNA-1345) Vaccine Clinical Trials
The pivotal ConquerRSV Phase 3 study of RSV in older adults (60+ years) the pivotal ConquerRSV study met both its primary efficacy endpoints, with vaccine efficacy (VE) of 83.7% (95.88% CI: 66.1%, 92.2%; p<0.0001) against RSV-LRTD as defined by two or more symptoms, and a VE of 82.4% (96.36% CI: 34.8%, 95.3%; p=0.0078) against RSV-LRTD defined by three or more symptoms. No Guillain-Barre Syndrome (GBS) cases have been reported with mRNA-1345 in the Phase 3 RSV trial. In addition to older adults, mRNA-1345 is being investigated in a fully enrolled, ongoing Phase 1 trial in pediatric populations.
Clinical Trial NCT04528719: A Dose Escalation Study to Evaluate Safety, Reactogenicity, and Immunogenicity of mRNA-1345 in Healthy Adults and Children Who Are Respiratory Syncytial Virus Seropositive. Estimated Completion Date: September 30, 2023. The study will be conducted in 2 phases: Phase 2 and Phase 3. In the Phase 2 segment, 400 and 2,000 participants will be randomly assigned to receive a single injection of either the mRNA-1345 vaccine at the selected dose or a placebo in a 1:1 randomization ratio.
On December 14, 2023, the New England Journal of Medicines published an Original Article that concluded a single dose of the mRNA-1345 vaccine led to a lower incidence of RSV-associated lower respiratory tract disease and RSV-associated acute respiratory disease than placebo among adults 60 years of age or older in a phase2/3 clinical trial. Vaccine efficacy was 83.7% (95.88% confidence interval [CI], 66.0 to 92.2) against RSV-associated lower respiratory tract disease with at least two signs or symptoms and 82.4% (96.36% CI, 34.8 to 95.3) against the disease with at least three signs or symptoms. Vaccine efficacy was 68.4% (95% CI, 50.9 to 79.7) against RSV-associated acute respiratory disease. Serious adverse events occurred in 2.8% of the participants in each trial group. On December 14, 2023, a New England Journal of Medicine op-ed discussed these results.
