Vaxart Announces Topline Data from the Phase 2 Challenge Study of its Monovalent Norovirus Vaccine Candidate
- Category: Vaccines
- Published on Thursday, 07 September 2023 10:03
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Study met 5 of 6 primary endpoints
Vaccine was safe and well tolerated with no vaccine-related serious adverse events (SAEs)
Vaccination led to a statistically significant reduction in infection rate, a non-statistically significant reduction in norovirus acute gastroenteritis (AGE), and a substantial reduction in viral shedding
SOUTH SAN FRANCISCO, CA, USA I September 06, 2023 I Vaxart, Inc. (Nasdaq: VXRT) today announced top-line data from the Phase 2 challenge study of its oral tablet monovalent norovirus vaccine candidate (NCT05212168).
The Phase 2 challenge study 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 led to a reduction in 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.
“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.”
Key Study Findings:
- Primary Endpoints:
- 29% reduction in the rate of infection in the vaccinated cohort compared with placebo (82% vs. 58%) (p=0.003)
- 21% reduction in the rate of norovirus AGE in the vaccinated cohort compared with placebo (45% vs. 57%) that was not statistically significant (p=0.149)
- Significant increase in the induction of norovirus-specific IgA antibody-secreting cells (ASC) in the vaccinated cohort, with a 79% response rate in the vaccinated cohort, compared with 2.5% in the placebo cohort (p<0.001) on Day 8 post-vaccination; mean response was 375 ASC per million cells for the vaccinated cohort, compared with 26 ASC per million cells for placebo
- Significant increase in the induction of HBGA blocking anti-bodies in the vaccinated cohort (GMFR 3.23) compared with the placebo cohort (GMFR 1.0) on Day 29 post-vaccination (p<0.001)
- Significant increases in norovirus-specific serum IgA (GMFR 7.14) and IgG (GMFR 4.64) in the vaccinated cohort compared with placebo from baseline to Day 29 post-vaccination (p<0.001)
- No vaccine-related SAEs or dose-limiting toxicities were reported, consistent with the safety profile observed in all of Vaxart’s norovirus trials
- Pre-specified Analysis:
- 85% decrease in viral shedding in the vaccinated cohort compared with placebo
- No statistically significant difference in disease severity in the vaccinated cohort compared with placebo
“The results of this study highlight the potentially distinctive profile of mucosal vaccination and the potential that our oral pill vaccines may have in protecting against infection and blocking transmission – potential benefits that have also been seen with our influenza vaccine. We are excited to further our understanding of these data and determine the optimal path forward for our norovirus program,” added Dr. Cummings.
Norovirus is the leading cause of acute viral gastroenteritis in all age groups in the U.S. However, there are no approved vaccines for noroviruses. In the U.S. alone, the annual disease burden from norovirus is $10.6 billion, as on average norovirus causes 19 to 21 million cases of AGE, infects 15% of all children under the age of 5, and leads to 465,000 emergency department visits, 109,000 hospitalizations and 900 deaths.
Vaxart believes the reduction in the rate of infection and increases in multiple immunologic endpoints in this challenge study support the potential for its norovirus vaccine program to provide significant public health benefit. The Company also believes that the numeric reduction in rate of AGE, while not statistically significant, is encouraging, especially given the high dose of challenge virus used in the study, compared with what would occur in a natural infection.
Vaxart is currently conducting additional analyses of the data from this challenge study and its prior norovirus trials with the objectives of defining the timing of a larger phase 2b study, and identifying ways to reduce the size and duration of a subsequent Phase 3 registration study.
Vaxart is a clinical-stage biotechnology company developing a range of oral recombinant vaccines based on its proprietary delivery platform. Vaxart vaccines are designed to be administered using pills that can be stored and shipped without refrigeration and eliminate the risk of needle-stick injury. Vaxart believes that its proprietary pill vaccine delivery platform is suitable to deliver recombinant vaccines, positioning the company to develop oral versions of currently marketed vaccines and to design recombinant vaccines for new indications. Vaxart’s development programs currently include pill vaccines designed to protect against norovirus, coronavirus, seasonal influenza, and respiratory syncytial virus (RSV), as well as a therapeutic vaccine for human papillomavirus (HPV), Vaxart’s first immune-oncology indication. Vaxart has filed broad domestic and international patent applications covering its proprietary technology and creations for oral vaccination using adenovirus and TLR3 agonists.