Vaxart Oral Pill Norovirus Vaccine (VXA-G1.1-NN)
Vaxart Inc.'s GI.1/GII.4 oral pill norovirus vaccine candidate consisting of monovalent GII.4 VXA-G2.4-NS and GI.1 VXA-G1.1-NN is designed to prevent illness from norovirus, a very contagious virus that causes vomiting and diarrhea. Norovirus GI.1 Norwalk VP1 Vaccine (VXA-G1.1-NN), an Oral E1/E3-Deleted Replication-Defective Recombinant Adenovirus serotype 5 with double-stranded ribonucleic acid (dsRNA) Adjuvant. The vaccine vector encodes for a full-length VP1 gene from Norwalk virus (NV). The adjuvant is a short hairpin RNA (shRNA), expressed as a 21 nucleotide sequence (GAAACGA TATGGGCTGAATAC) as a tandem sequence in forward and reverse orientations separated by six nucleotides that comprise the loop of the RNA. The final drug product is formulated into an enteric-coated tablet.
Preliminary clinical trial results announced on July 6, 2023, showed robust serum immune responses across all doses at Day 29 relative to Day 1. Both doses showed a similar increase in serum antibody responses with no statistical difference between the medium and high dose arms. At Day 29, increases in serum IgA, IgG, and BT50 for both the GII.4 and GI.1 strains in the vaccine arms were similar to those seen in previous norovirus studies conducted by Vaxart. On September 6, 2023, the Company announced top-line data from the Phase 2 challenge study (NCT05212168) that enrolled 165 healthy adults who were randomized 1:1 to receive Vaxart's monovalent oral tablet vaccine targeting the norovirus GI.1 genotype or placebo. Four weeks after vaccination, subjects were challenged with GI.1 norovirus. The study achieved its primary endpoints of a statistically significant 29% reduction in the rate of norovirus infection between the vaccinated and placebo arms through Day 8 post-challenge, a strong induction of norovirus-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies, and other immune response endpoints. Vaccination also reduced norovirus AGE in the vaccine arm compared to placebo, but this was not statistically significant. In a prespecified analysis, the study also showed an 85% decrease in viral shedding in the vaccine arm compared with placebo.
The Phase 2b study (VXA-NVV-201) is expected to add safety data that, if successful, will then enable Vaxart to schedule an End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA), potentially in 2024. Data from the Phase 2 study and a future Phase 3 study are required for a Biologics License Application (BLA) submission to the FDA as the Company pursues a commercial pathway for its bivalent norovirus candidate. On November 2, 2023, Vaxart announced it launched a phase 1 study evaluating the ability of oral vaccine tablets to induce breast milk antibodies and transfer antibodies to infants.
South San Francisco, CA-based Vaxart Inc. is a clinical-stage biotechnology company developing a range of oral recombinant vaccines based on its proprietary delivery platform.
Norovirus is the leading cause of acute viral gastroenteritis in all age groups in the U.S. Vaxart believes a vaccine that produces mucosal antibodies locally in the intestine and systemic antibodies circulating in the blood may better protect against norovirus infection than an injectable vaccine.
Dose: 1x10E11 IU±0.5 log. Adverse event rates for doses were similar to placebo in clinical trials.
VXA-G1.1-NN Adverse Events
The Phase 2 dose-ranging study also demonstrated that the bivalent norovirus vaccine candidate was well tolerated, with a favorable safety profile that included no vaccine-related serious adverse events and no dose-limiting toxicity.
November 2, 2023: Dr. James F. Cummings, Vaxart's chief medical officer, comments, "We believe an oral norovirus vaccine pill may one day allow mothers to protect their infants against this highly contagious virus for which there currently is no approved vaccine."
September 6, 2023 - "Challenge studies use higher quantities of virus than an individual may encounter during a naturally occurring infection, yet our vaccine candidate demonstrated a significant effect on infection and viral shedding, even though it did not achieve a statistically significant reduction in norovirus AGE," said Dr. James F. Cummings, Vaxart's Chief Medical Officer. "The magnitude of the reduction in shedding could have an impact on transmission and may have important public health benefits, as norovirus spreads rapidly among people gathering in large numbers, including settings such as daycare centers, nursing homes, and workplaces, and may reduce the potential spread of the infection to families at home."
VXA-G1.1-NN Clinical Trials
Phase 1 multicenter, randomized, double-blind, placebo-controlled single dose, dose-ranging study is designed to evaluate the safety, tolerability, and immunogenicity of orally administered bivalent GI.1/GII.4 norovirus vaccine in healthy lactating females of at least 18 years of age and their breast-feeding infants (aged 30 days to 11 months). The study is expected to enroll approximately 76 subjects at seven sites in South Africa. Subjects will be randomized into high- or low-dose vaccine (N=30 for each arm) or placebo (N=16).
This is a phase 2b randomized, double-blind, placebo-controlled vaccination and challenge study to assess the protective efficacy of the Vaxart Norovirus vaccine (VXA-G1.1-NN). Healthy adults will be randomized in a 1:1 ratio to receive one oral dose of vaccine or placebo.
Clinical Trial NCT03897309: Safety & Immunogenicity Study of Ad5 Based Oral Norovirus Vaccines (VXA-NVV-103)
Clinical Trial NCT02868073: Phase 1 Placebo-controlled, Randomized Trial of an Adenoviral-vector Based Norovirus Vaccine (Completed)
Clinical Trial NCT03125473: Dose-Optimization Trial of VXA-G1.1-NN in Healthy Volunteers (Completed).