Breakthrough Clinical Results
Vaxart, Inc. announced positive topline results from a Phase 1 clinical trial evaluating its second-generation oral pill norovirus vaccine. The trial demonstrated statistically significant increases in norovirus blocking antibodies (NBAA) titers compared to its first-generation vaccine in healthy volunteers. The second-generation vaccine candidates were safe and well-tolerated. These results support the potential for improved protection against norovirus infection and Vaxart plans to advance the vaccine candidate into a Phase 2b study, pending partnership or funding.
Key Highlights
- Statistically significant increases in GI.1 and GII.4 norovirus blocking antibodies (141% and 94%, respectively) compared to the first-generation vaccine.
- Vaccine candidates were safe and well-tolerated with no vaccine-related serious adverse events.
- Vaxart plans to conduct a Phase 2b safety and immunogenicity study in the second half of 2025, pending funding.
- The second-generation technology improved antibody responses in animal models and has been implemented across Vaxart's vaccine portfolio.
Economic Burden
Norovirus infections impose a substantial economic burden globally, with the majority of the burden stemming from productivity losses due to acute illness.
United States:
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A 2022 study estimated the total cost of norovirus in the US to be $10.6 billion annually. This includes $0.2-$2.3 billion in direct medical costs and $1.4-$20.7 billion in productivity losses. Sporadic cases account for over 90% of this burden, with productivity losses representing 89% of the total. More than half of the economic burden occurs in adults aged 45 and older, and more than half occurs during the winter months. Over 90% of outbreak costs are due to person-to-person transmission.
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An earlier study (2017) estimated annual costs of $4.2 billion in direct health system costs and $60.3 billion in societal costs globally. The US, being a high-income country, generated a significant portion of these global costs. The study highlighted that while disease incidence is similar across income levels, high-income countries bear a larger proportion of the global health system costs.
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Another study from 2015 estimated 900 deaths, 109,000 hospitalizations, 465,000 emergency department visits, and 2.3 million ambulatory clinic encounters annually due to norovirus, with associated healthcare charges of $430-740 million.
Europe:
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A 2017 study estimated the global economic burden of norovirus to be $4.2 billion in direct health system costs and $60.3 billion in societal costs annually. This study included European countries within its global analysis, but did not provide specific cost estimates for Europe as a whole or for individual European nations. The study emphasized the significant contribution of productivity losses (84-99% of total costs) to the overall burden, varying by region.
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A 2014 study estimated that human norovirus infections cost $2 billion annually in the USA and led to a loss of approximately 5000 quality-adjusted life-years. The highest cost among 14 foodborne pathogens is also attributed to human NoV in The Netherlands.
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A 2017 study focused on the burden of norovirus gastroenteritis in China, but did not provide specific data on European countries. However, it highlighted the global nature of the economic problem posed by norovirus.
It is important to note that these studies used different methodologies and considered different cost components, which can contribute to the variability in the estimates. Additionally, the burden of norovirus can fluctuate annually depending on the incidence of sporadic cases.
Second-generation oral rAd5 vaccines are being investigated for several other indications besides norovirus, including influenza and SARS-CoV-2. While the provided texts don't detail specific intervention models for each trial, they do offer some general information:
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Nonreplicating human recombinant adenovirus type-5 (rAd5) vector: This is the core technology for these oral vaccines. It delivers the genetic material encoding viral proteins (like norovirus VP1) to the small intestine, stimulating a mucosal immune response.
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Oral administration: This is a key advantage of these vaccines, as it allows for easier administration and potentially better mucosal immunity compared to injected vaccines.
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Prime and boost: At least for the norovirus vaccine (VXA-G1.1-NN), a prime-boost regimen was used in older adults, with doses given 28 days apart. This is a common strategy to enhance and prolong immune responses.
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Dose levels: The norovirus trial in older adults explored three different dose levels, suggesting dose optimization is part of the investigation.
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Clinical trial phases: The provided texts mention Phase I trials for oral norovirus vaccines and Phase IIb trials for intramuscular bivalent norovirus vaccines. This indicates these vaccines are undergoing rigorous clinical testing to assess safety and efficacy.
More specific details about the intervention models for influenza and SARS-CoV-2 oral rAd5 vaccines would require consulting the cited publications or other relevant sources.