Moderna recently provided an update on regulatory submissions for mRNA-1345, a vaccine for the prevention of RSV-associated lower respiratory tract disease (RSV-LRTD) and acute respiratory disease in adults aged 60 years or older.

Moderna has submitted marketing authorization applications for mRNA-1345 with the European Medicines Agency, Swissmedic, in Switzerland, and the Therapeutic Goods Administration (TGA) in Australia and has initiated the rolling submission process for a Biologics License Application to the FDA for the licensure of the mRNA-based RSV vaccine.

mRNA-1345 is an investigational RSV vaccine that contains a single mRNA sequence encoding for a stabilized prefusion F glycoprotein. The vaccine utilizes the same lipid nanoparticles that are in the Moderna COVID-19 vaccines. The F glycoprotein is on the surface of the virus and is needed 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 the protein sequences are largely comparable across both RSV-A and RSV-B subtypes.

Stéphane Bancel, CEO of Moderna, stated, “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.”

Mr. Bancel added, “Our mRNA platform has allowed us to move from initial clinical testing to our first international Phase 3 trial to initiation of regulatory submissions for mRNA-1345 in just two years, enabling us to tackle this pervasive public health burden with speed and clinical rigor. mRNA-1345 represents the second product coming from our mRNA platform to seek global approval, and with recent positive data in rare disease and cancer, we expect more in the future—further demonstrating the tremendous potential of mRNA to combat disease.”

The regulatory applications are established on positive data from a prespecified interim analysis of the pivotal ConquerRSV study—a randomized, double-blind, placebo-controlled study of approximately 37,000 adults aged 60 years or older in 22 countries.

The primary efficacy endpoints were based on two definitions of RSV-LRTD, defined as either two or more symptoms or three or more symptoms of the disease. The trial met both its primary efficacy endpoints, with a vaccine efficacy (VE) of 83.7% (95.88% CI; 66.1%, 92.2%; P <.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 = .0078) against RSV-LRTD defined by three or more symptoms.

The vaccine was well tolerated with a favorable safety profile. Most solicited adverse reactions were mild or moderate, and the most frequently reported solicited adverse reactions in the mRNA-1345 group were injection-site pain, fatigue, headache, myalgia, and arthralgia.

The ConquerRSV study is ongoing, and additional efficacy analyses are planned as cases accrue, including for severe RSV. In addition to older adults, mRNA-1345 is being investigated in a fully enrolled, ongoing phase I trial in pediatric populations.

In January 2023, the FDA granted mRNA-1345 Breakthrough Therapy Designation for the prevention of RSV-LRTD in adults aged 60 years or older, and mRNA-1345 was previously granted Fast Track designation by the FDA in August 2021. 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.

Moderna’s respiratory disease vaccine pipeline includes phase III trials against influenza and a next-generation COVID-19 candidate. The pipeline also includes four additional influenza vaccines with expanded antigens, vaccines against other respiratory pathogens, and five combination vaccine programs.

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