mRNA-1345 RSV Vaccine 2023

Moderna Inc.'s 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 make small pieces of proteins. In addition, this vaccine candidate 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.

The Company shared the first interim analysis of the Phase 1 study of mRNA-1345, through 1-month post-vaccination, of the younger adult cohorts on April 14, 2021. Results showed the vaccine candidate generated a geometric mean rise in neutralizing antibodies relative to a baseline of at least 11-fold. On February 22, 2022, Moderna announced that the tRSV program's Data and Safety Monitoring Board (DSMam endorsed the start of the Phase 3 portion of the pivotal clinical study of mRNA-1345. Moderna's pivotal placebo-controlled Phase 3 clinical study of mRNA-1345 evaluates its effectiveness in older adults (60 yrs+). As of July 2023, the ConquerRSV study met primary efficacy endpoints, demonstrating vaccine efficacy of 83.7% against RSV lower respiratory tract disease in older adults.

On July 5, 2023, Moderna announced it had submitted marketing authorization applications for mRNA-1345 with the European Medicines Agency, Swissmedic, and the Therapeutic Goods Administration (TGA) in Australia. In Australia, the TGA submission will be evaluated under the Priority Pathway following approval of the Priority Determination application for mRNA-1345 in April 2023. The Company has also initiated a rolling submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for mRNA-1345. The FDA previously granted Fast Track and Breakthrough Designation designations for mRNA-1345 in adults older than 60. The Company announced on August 3, 2023, that it continues to expect a 2024 launch of its RSV vaccine and, has initiated a rolling submission process for a BLA with the U.S. FDA, and expects an April 2024 PDUFA date. On September 13, 2023, the Company stated regulatory applications were also submitted in Europe (EMA), Switzerland (Swissmedic), Australia (TGA), Canada (Health Canada), and the United Kingdom (MHRA).

On October 25, 2023, the U.S. Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) confirmed the Work Group will begin reviewing the safety and efficacy of Moderna's mRNA-1345 for use in adults 60 and older.

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.

mRNA-1345 Vaccine Sales Forecast

According to GlobalData plc sales forecast published on July 24, 2023, the mRNA-1345 vaccine is expected to launch in 2024 and experience exponential growth to reach sales of $2.4 billion in 2029. The mRNA-1345 vaccine will be provided to customers in ready-to-use pre-filled syringes.

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.

mRNA-1345 Dosage

The interim 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. Data were pooled across dose levels because there was no significant difference between doses.

mRNA-1345 Safety and Efficacy

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.

mRNA-1345 News 2023

September 13, 2023 - The Company confirmed mRNA-1345 is being investigated in a fully enrolled, ongoing Phase 1 trial in pediatric populations.

August 3, 2023 - Stéphane Bancel, Chief Executive Officer of Moderna, commented, "Our late-stage clinical pipeline is firing on all cylinders with four infectious disease vaccines in Phase 3, including RSV, which was recently submitted to regulators for approval."

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 can cause a significant burden to health systems through hospitalizations and emergency care admissions," said Stéphane Bancel, Chief Executive Officer of Moderna, in a press release.

April 11, 2023 - Moderna announced that mRNA-1345 is in an ongoing Phase 2/3, randomized, observer-blind, placebo-controlled case-driven trial (ConquerRSV) in adults 60 and older. In this study, 35,541 participants from 22 countries were randomized 1:1 to receive one dose of mRNA-1345 or placebo.

January 30, 2023 - Stéphane Bancel, CEO of Moderna, stated: "With this designation, we look forward to productive conversations with the FDA in the hopes of bringing our RSV vaccine candidate for older adults to the market safely and quickly. Moderna's mRNA platform has now demonstrated two positive Phase 3 infectious disease trial results, and we continue to advance a portfolio of respiratory mRNA vaccines targeting the most serious diseases. We are grateful to the FDA for this designation."

January 17, 2023 - Stéphane Bancel, Moderna's CEO, stated: "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." mRNA-1345 demonstrated vaccine efficacy of 83.7% against RSV lower respiratory tract disease, defined by two or more symptoms in older adults.

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.

March 9, 2022 - ConquerRSV, a pivotal Phase 3 trial in adults ≥ 60 years of age; expected enrollment is ~34,000 participants in multiple countries.

February 24, 2022 - Moderna, Inc. reported full-year 2021 revenues of $18.5 billion.

February 22, 2022 - Stéphane Bancel, CEO of Moderna, stated in a press release, "Our ultimate goal is to combine our RSV vaccine with our COVID-19 and flu boosters into a single-dose booster."

November 18, 2021 - Moderna, Inc. announced the first participant had been dosed in the ConquerRSV Phase 2/3 study of mRNA-1345, the Company's Respiratory Syncytial Virus (RSV) vaccine candidate.

November 4, 2021 - Moderna announced a pivotal Phase 2/3 study of respiratory syncytial virus (RSV) vaccine candidate (mRNA-1345) in older adults expected to begin in 2021; the study is expected to enroll approximately 34,000 participants, subject to agreement with regulatory authorities.

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.

May 6, 2021 - Moderna Inc., investor presentation regarding mRNA-1345 vaccine candidate.

April 14, 2021 - Moderna shared the first interim analysis of the Phase 1 study after 1-month post-vaccination of younger adults (18-49). 'mRNA-1345 was shown to increase RSV neutralizing antibodies in seropositive younger adults. As expected, neutralizing antibodies were confirmed to be present at baseline in all participants. In addition, a single vaccination of mRNA-1345 at the 50 or 100 μg dose level boosted neutralizing antibody titers against both serotypes of RSV-A and RSV-B with no apparent dose-response. At month 1, the geometric mean fold rise in neutralizing antibody relative to baseline was at least 20.5 for RSV-A and 11.7 for RSV-B.'

mRNA-1345 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.