Moderna, Inc. has announced the commencement of the Phase 3 Nova 301 trial for its investigational norovirus vaccine, mRNA-1403. The global study is designed to evaluate the efficacy, safety, and immunogenicity of the mRNA vaccine in preventing moderate to severe acute gastroenteritis (AGE) caused by the norovirus in adults.
The Nova 301 trial is a randomized, observer-blind, placebo-controlled study planning to enroll approximately 25,000 participants aged 18 years and older across various regions, including the U.S., Canada, the UK, Japan, Australia, and South America. A key focus is on enrolling 20,000 participants aged 60 years and older, who are at a higher risk of severe outcomes, including hospitalization, from norovirus infection. The trial is part of a 10-year strategic partnership between Moderna and the UK Health Security Agency (UKHSA).
Addressing a Significant Public Health Burden
Norovirus is a highly contagious virus and a leading cause of diarrheal disease worldwide. It is associated with approximately 18% of all acute gastroenteritis (AGE) cases, resulting in an estimated 200,000 deaths per year and substantial healthcare costs. Symptoms include vomiting, diarrhea, and stomach cramps, which can lead to severe dehydration, particularly in vulnerable populations such as young children and older adults.
"Norovirus is a significant public health concern that affects millions of people worldwide each year, leading to severe symptoms and, in some cases, hospitalization," said Stéphane Bancel, CEO of Moderna. "By advancing our investigational norovirus vaccine into a pivotal Phase 3 trial, we are one step closer to potentially providing a new tool to prevent infection from this highly contagious virus, which places a significant burden on health systems globally."
mRNA-1403: A Trivalent Vaccine Candidate
mRNA-1403 is an mRNA vaccine in development to prevent moderate to severe acute gastroenteritis caused by norovirus. The vaccine candidate is a trivalent formulation containing mRNA that encodes for virus-like particles (VLPs) designed to protect against multiple norovirus genotypes. This approach aims to address the challenges posed by the virus's broad and shifting genotype diversity, which has historically hindered the development of effective vaccines.
Promising Phase 1/2 Data
Moderna presented interim results from an ongoing Phase I/II trial (NCT05992935) at IDWeek 2024, which showed promising safety, reactogenicity, and immunogenicity data for mRNA-1403. The vaccine elicited robust serum HBGA-blocking antibody responses against all three NoV genotypes and across all dose levels. Similar findings were observed for both younger and older adults, with older adults accounting for over 40% of trial participants. No major safety concerns were identified through eight months of follow-up for Phase I and one month of follow-up for Phase II.
Potential Timeline and Impact
If the Phase 3 trial is successful, Moderna anticipates submitting a marketing application to regulators in 2026. A successful vaccine could significantly reduce the burden of norovirus, preventing millions of infections and hospitalizations each year. Dr. Doran Fink of Moderna stated that an efficacy of at least 65% would be considered clinically meaningful.
Other Norovirus Vaccine Candidates
While Moderna's mRNA-1403 is a frontrunner, there are other norovirus vaccine candidates in late-stage development, including those from Vaxart and Chongqing Zhifei Biological Products. However, the broad genotype diversity of norovirus remains a challenge for all vaccine developers.
