Vaxart’s Second-Generation Oral Norovirus Vaccine Shows Strong Mucosal Response in Phase 1

Vaxart reported new phase 1 head-to-head data showing its second-generation oral norovirus pill generated larger mucosal responses after a single tablet than its first-generation constructs. At the high dose, fecal IgA rose 25-fold for GII.4 and 10-fold for GI.1 (8-fold and 7-fold at the low dose), compared with prior first-generation highs of 13-fold and 6-fold; June results also showed higher blocking-antibody levels for the newer constructs (+141% GI.1; +94% GII.4). The phase 1 study was not powered for statistical superiority and had no clinical endpoints, so efficacy remains unconfirmed despite earlier first-generation challenge data showing a 30% relative reduction in infection versus placebo.

In this interview with Sean N. Tucker, PhD, founder and CSO of Vaxart, we discussed: the prespecified phase 1 immunogenicity endpoints (including assays used) and how the data were analyzed; the evidence linking fecal IgA and blocking antibodies to protection across GI.1 and GII.4 and how phase 2b will test these markers against clinical outcomes and durability; and the planned phase 2b design, target population, dosing schedule, strain coverage, and safety monitoring, along with the timeline and funding path for advancing to phase 3.

According to the company’s plan, a phase 2b safety and immunogenicity study could begin as early as late 2025 (funding dependent), followed by an end-of-phase-2 FDA meeting and a potential phase 3 in 2026.

Reference

Vaxart. Vaxart Reports Additional Phase 1 Data Supporting the Potential Efficacy of its Second-Generation Norovirus Oral Pill Vaccine Candidate. September 10, 2025. Accessed September 16, 2025. https://investors.vaxart.com/news-releases/news-release-details/vaxart-reports-additional-phase-1-data-supporting-potential