Vaxart reported additional Phase 1 head-to-head data indicating its second-generation oral pill norovirus constructs produced larger fecal IgA responses after a single tablet per strain. High dose increased fecal IgA 25-fold for GII.4 and 10-fold for GI.1; low dose rose 8-fold and 7-fold, respectively. Fecal IgA has been identified as a correlate of protection in Vaxart’s Phase 2b challenge study.
The study was not powered for statistical superiority, but second-generation responses compared favorably with first-generation constructs at the same high dose, which previously rose 13-fold for GII.4 and 6-fold for GI.1 over baseline. In June 2025, Vaxart also reported higher blocking-antibody levels for the second generation, up 141% for GI.1 and 94% for GII.4 versus first generation. Earlier phase 2b challenge data with the first generation showed a 30% relative reduction in infection versus placebo.
Sean Tucker, PhD, founder and chief scientific officer, presented the data at the 9th International Calicivirus Conference in Banff, Canada, held September 7–11, 2025. Becca Flitter, PhD, presented additional findings from Vaxart’s norovirus challenge study.
Vaxart plans a phase 2b safety and immunogenicity study, contingent on a partnership or other funding, with potential start before the end of 2025. The company anticipates an end-of-Phase-2 meeting with the FDA and says a phase 3 trial could begin as early as 2026.
What You Need To Know
The second-generation oral candidate showed larger mucosal responses after a single dose than the first-generation, though the study wasn’t designed to demonstrate superiority.
Functional antibody findings favor the newer constructs, while prior challenge data with the first-generation suggested reduced infection, but efficacy remains unconfirmed.
The program is advancing to mid-stage evaluation with potential late-stage trials to address the lack of an approved norovirus vaccine.
There is no approved vaccine for norovirus, a leading cause of acute gastroenteritis that accounts for an estimated 685 million infections worldwide each year, including 20 million annually in the United States. Norovirus is believed to cause nearly 20% of diarrheal disease. The economic burden is estimated at 60 billion dollars globally and 10 billion dollars in the United States.
The Phase 1 head-to-head results suggest the second-generation oral constructs elicit numerically greater mucosal fecal IgA and functional blocking antibody responses than the first-generation constructs. Because the trial was not powered for superiority and did not assess clinical endpoints, efficacy remains unproven and will require confirmation in phase 2 and phase 3 studies.
A Phase 1b study of the first-generation oral pill in adults aged 55 to 80 years reported significant increases in serum anti-VP1 IgA and IgG, mucosal immunity in saliva and nasal samples, and T-cell responses, with immune responses similar to those observed in younger adults. In a human challenge setting, the platform reduced viral shedding, supporting the potential relevance of mucosal and blocking-antibody responses.
For additional context on mucosal immunity and development plans, listen to our March interview with Sean N. Tucker, PhD: Vaxart’s Oral Norovirus Vaccine: Key Study Findings and Future Plans
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