Vaxart Oral Pill Bivalent Norovirus Vaccine Clinical Trials, Dosage, Indication, News, Side Effects
Vaxart Inc.'s GI.1/GII.4 oral pill bivalent 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. Vaxart's vaccine is differentiated from other norovirus vaccine candidates because it generates systemic and mucosal immunity delivered through the mouth and is stable at room temperature.
Vaxart reported topline data from the Phase 1 clinical trial focused on lactating mothers on April 30, 2024. Antibodies to norovirus rose on average 4-fold for the G1.1 virus strain and 6-fold for the GII.4 virus strain in the breast milk of lactating mothers who received the Vaxart vaccine candidate in the high dose group. There were no vaccine-related serious adverse events and no dose-limiting pharmacotoxicity.
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 topline 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.
Data from the Phase 2 study (VXA-NVV-201) and a future Phase 3 study are required for a Biologics License Application submission to the U.S. Food and Drug Administration as the Company pursues a commercial pathway for its bivalent norovirus candidate.
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. 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.
Vaxart Oral Bivalent Norovirus Vaccine Indication
Norovirus is the leading cause of acute viral gastroenteritis in all age groups in the U.S. Approximately 3 million parents are forced by norovirus infections to miss work, approximately 2.2 days on average, to care for their children. The annual disease burden from norovirus is $10.6 billion in the U.S. alone. Globally, norovirus has become the leading cause of pediatric gastroenteritis in healthcare settings in countries adopting a rotavirus vaccine program.
Vaxart Oral Bivalent Norovirus Vaccine Dose
Dose: 1x10E11 IU±0.5 log. Adverse event rates for doses were similar to placebo in clinical trials.
Vaxart Oral Bivalent Norovirus Vaccine 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.
Vaxart Oral Bivalent Norovirus Vaccine News
April 30, 2024—Dr. James F. Cummings, VaVaxart'shief Medical Officer, commented in a press release: “I" can be difficult to immunize the youngest children mucosally because the immune system is still developing. Passive transfer of antibodies from mothers to infants via breast milk is an innovative approach to improve infection resistance in infants potentially.”
December 21, 2023 - "This is an important step forward as we drive toward a vaccine candidate that may make it possible for mothers to protect their children against this highly contagious – and potentially lethal -- virus. We look forward to announcing topline data from this study by the end of 2024," said Dr. James F. Cummings, Vaxart's Chief Medical Officer.
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," "aid Dr. James F. Cummings, VaVaxart'shief Medical Officer.
Vaxart Oral Bivalent Norovirus 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).
