Pivotal Trial Results Show Efficacy of mRNA Vaccine for Respiratory Syncytial Virus
A single dose of mRNA-1345 produced lower incidence of respiratory syncytial virus-associated lower respiratory tract disease and RSV-associated acute respiratory disease.
Image credit: photoopus | stock.adobe.com
The results of a pivotal Phase III trial show favorable clinical safety and efficacy data for Moderna’s investigational respiratory syncytial virus (RSV) vaccine mRNA-1345. In findings published in The New England Journal of Medicine, a single dose of the vaccine produced lower incidence of RSV-associated lower respiratory tract disease (LRTD) as well as RSV-associated acute respiratory disease compared with placebo in those aged 60 years and older.1
mRNA-1345 consists of a single mRNA sequence encoding for a stabilized prefusion F glycoprotein and uses the same lipid nanoparticles as the Moderna COVID-19 vaccines. In July, Moderna filed marketing authorization submissions for mRNA-1345 for the prevention of RSV-associated LRTD and acute respiratory disease in adults aged 60 years and older.2
The company submitted the applications for the vaccine with the European Medicines Agency, Swissmedic in Switzerland, and the Therapeutic Goods Administration (TGA) in Australia. It also initiated the rolling submission process for a biologics license application to the FDA for the licensure of the vaccine. In January 2023, the FDA awarded mRNA-1345 with breakthrough therapy designation to prevent RSV-LRTD in adults aged 60 years or older. The novel vaccine was previously granted fast track designation in 2021.
The ongoing, randomized, double-blind, placebo-controlled, Phase II–III trial randomly assigned on a 1:1 basis adults aged 60 years or older to receive one dose of 50 μg mRNA-1345 (17,793 patients) or placebo (17,748 patients). The trial’s primary efficacy endpoints were prevention of RSV-associated LRTD with at least two signs or symptoms and with at least three signs or symptoms. The secondary efficacy endpoint was prevention of RSV-associated acute respiratory disease.
The results showed that a single dose of mRNA-1345 produced 83.7% efficacy against RSV-associated LRTD with at least two signs or symptoms, 82.4% efficacy against RSV-associated LRTD with at least three signs or symptoms, and 68.4% against RSV-associated acute respiratory disease. Researchers observed protection against RSV subtypes A and B, with consistent findings across subgroups defined by age and coexisting conditions.
The mRNA-1345 patient cohort showed a higher incidence of solicited local adverse events (AEs) at 58.7% compared to 16.2% in the placebo cohort. Systemic AEs were 47.7% in the investigational cohort compared to 32.9% with placebo, but were deemed mild to moderate and were temporary. Serious AEs were reported in 2.8% of the participants in each trial group.
An accompanying editorial published in The New England Journal of Medicine noted the importance of an effective preventative option against RSV globally.
“The burden of RSV disease in older adults in the United States and worldwide is substantial, and multiple RSV vaccines will provide an important intervention in this age group,” the study authors wrote.3 “However, the effects of RSV infection are most profound in infants, with at least 100,000 potentially preventable deaths each year, 97% of which occur in low- and middle-income countries. The vaccination of pregnant persons with RSV vaccines can protect their young infants by means of the placental transfer of antibodies.”
References
1. Wilson E, et al. Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults. Journal Article. 2023. New England Journal of Medicine. PG - 2233-2244. VI - 389 IP - 24 DOI: 10.1056/NEJMoa2307079. https://www.nejm.org/doi/full/10.1056/NEJMoa2307079. December 14, 2023 389(24):2233. Accessed December 18, 2023.
2. Moderna announces global regulatory submissions for its respiratory syncytial virus (RSV) vaccine, mRNA-1345. News release. Moderna. July 5, 2023. Accessed December 18, 2023. https://investors.modernatx.com/news/news-details/2023/Moderna-Announces-Global-Regulatory-Submissions-For-Its-Respiratory-Syncytial-Virus-RSV-Vaccine-MRNA-1345/default.aspx
3. Cohn, A. Hall, A. Continued Progress in the Development of Safe and Effective RSV Immunizations. Journal Article. 2023. New England Journal of Medicine. PG - 2289-2290. VI -389. IP – 24. DOI: 10.1056/NEJMe2311862. https://www.nejm.org/doi/full/10.1056/NEJMe2311862. December 14, 2023 389(24):2289. Accessed December 18, 2023.
Merck Launches Phase III Trials of Once-Monthly Oral HIV PrEP Candidate MK-8527
July 14th 2025In the new EXPrESSIVE clinical trial program, Merck will evaluate MK-8527, a once-monthly, oral PrEP therapy, in populations at high risk of HIV-1 infection, including adolescent girls and women in sub-Saharan Africa.
Unifying Industry to Better Understand GCP Guidance
May 7th 2025In this episode of the Applied Clinical Trials Podcast, David Nickerson, head of clinical quality management at EMD Serono; and Arlene Lee, director of product management, data quality & risk management solutions at Medidata, discuss the newest ICH E6(R3) GCP guidelines as well as how TransCelerate and ACRO have partnered to help stakeholders better acclimate to these guidelines.
Baxdrostat Shows Significant Blood Pressure Reduction in Phase III BaxHTN Trial
July 14th 2025In the BaxHTN Phase III study, AstraZeneca’s baxdrostat demonstrated statistically significant and clinically meaningful reductions in systolic blood pressure in patients with uncontrolled or treatment-resistant hypertension.
New FDA Initiative Reveals Common Reasons for Drug Application Rejection
July 11th 2025By publishing more than 200 complete response letters, the FDA is offering new visibility into the issues that most often delay drug approvals, including safety concerns, trial design flaws, and manufacturing gaps.
Arcus’ Quemliclustat Earns Orphan Drug Designation as Phase III Pancreatic Cancer Trial Advances
July 11th 2025The FDA has granted orphan status to Arcus Biosciences’ CD73 inhibitor quemliclustat for metastatic pancreatic cancer, as the global PRISM-1 Phase III trial nears full enrollment following promising survival data from ARC-8.
