Moderna is advancing its norovirus vaccine candidate, mRNA-1403, into a Phase 3 clinical trial (Nova 301) as norovirus cases surge across the United States. The trial, which began in September, seeks to enroll 25,000 adult participants globally, including 20,000 individuals aged 60 and older, who are at higher risk of severe norovirus infection. Results from the trial are anticipated as early as late 2025 or 2026. This development comes at a crucial time, with the CDC reporting a significant increase in norovirus test positivity rates, reaching nearly 23% in late December.
Addressing a Critical Unmet Need
Norovirus, often referred to as the "stomach bug" or "cruise-ship virus," is the leading cause of vomiting, diarrhea, and foodborne illness in the U.S. According to the CDC, it affects up to 21 million people annually, leading to 465,000 emergency department visits, 109,000 hospitalizations, and 900 deaths, primarily among older adults. Currently, there is no FDA-approved vaccine for norovirus, making prevention challenging.
"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, in a prior statement. He emphasized the potential of the Phase 3 trial to provide a new tool to prevent infection from this highly contagious virus.
The Nova 301 Trial: Design and Objectives
The Nova 301 trial is a randomized, double-blinded, placebo-controlled study designed to evaluate the safety, efficacy, and immunogenicity of mRNA-1403. Participants will receive a single injection of either the vaccine candidate or a placebo in the upper arm. The trial spans approximately two years, involving multiple in-person visits and phone calls to monitor safety and collect data. Participants will also be required to maintain a symptom log and may be asked to provide stool samples if they experience norovirus-like symptoms.
The primary goal of mRNA-1403 is not necessarily to prevent infection entirely, but to reduce the severity of symptoms and prevent complications requiring medical intervention. Moderna is focusing on vaccinating seniors and other vulnerable populations, such as healthcare workers and daycare providers, who are at increased risk of severe outcomes.
mRNA Technology: A Potential Game-Changer
Moderna's mRNA vaccine technology offers a potential advantage in addressing the challenges of norovirus vaccine development. As Dr. Doran Fink, Moderna's clinical therapeutic area head for gastrointestinal and bacterial pathogens, explained, traditional protein-based vaccines involve injecting purified proteins to stimulate an immune response. In contrast, mRNA vaccines instruct the body's cells to produce the target protein, in this case, virus-like particles (VLPs) that resemble norovirus but are non-infectious. This approach may allow for more rapid adaptation to evolving norovirus strains.
While the current vaccine candidate targets three common norovirus genotypes, one of the study's goals is to assess whether it provides broader protection against other strains as well. The flexibility of mRNA technology allows for easier modification of the vaccine to address emerging variants, if needed.
Challenges and Future Directions
Developing a norovirus vaccine has been historically challenging due to the virus's rapid mutation rate and the lack of long-lasting immunity following infection. However, recent advances in understanding norovirus biology and immunology have paved the way for promising vaccine candidates like mRNA-1403.
Luca Issi, an analyst at RBC, noted that the commercial viability of a norovirus vaccine remains a key question for investors. The initial target populations are likely to be individuals in nursing homes and those going on cruises, where norovirus outbreaks are common. While Moderna is not currently testing the vaccine in children, future studies in this population may be warranted if the vaccine proves effective in adults.
