COVID-19 Pill Vaccine Candidate Posts Positive Phase 2 Study Results

California-based Vaxart, Inc. today reported positive top-line data from the first part of a planned two-part Phase II study of its Wuhan S-only oral pill COVID-19 vaccine candidate, VXA-CoV2-1.1-S.

The data released on September 1, 2022, demonstrate that the clinical trial met its primary safety and secondary immunogenicity endpoints.

Serum neutralizing antibodies rose after oral vaccination, and the increases were particularly notable in subjects who had previously received an mRNA vaccine.

Additionally, all subjects with a mucosal immune response to the Wuhan-based vaccine had mucosal immune responses that cross-reacted with the Omicron variants, including BA 4/5, and other coronaviruses.

Study Key Findings:

• The VXA-CoV2-1.1-S vaccine construct was safe and well-tolerated.
• In addition, no vaccine-related solicited grade 3 adverse events (AEs) and no vaccine-related serious adverse events (SAEs) were reported.
• Vaccination with VXA-CoV2-1.1-S increased levels of SARS-CoV-2-specific serum IgG and IgA antibodies at Days 29 and 57.
• The geometric mean titer (GMT) increase of SARS-CoV-2-specific serum neutralizing antibodies from Day 1 to Day 57 ranged by cohort between 1.2- and 2-fold, with higher increases for higher doses.
• Among 18-55-year-old subjects previously vaccinated with mRNA vaccines, the geometric mean titer (GMT) of SARS-CoV-2-specific serum neutralizing antibodies increased 1.6-fold, from 481 AU/ml at Day 1 to 778 AU/ml at Day 57. The subjects with lower starting titers showed more significant increases after oral boosting.  
• Approximately 50% of all subjects and 50% of subjects that previously received an mRNA vaccine had at least a 1.5-fold increase in mucosal IgA antibodies.
• All subjects who had a mucosal response to Wuhan S from VXA-CoV2-1.1-S (a Wuhan-based vaccine) also had mucosal immune responses that cross-reacted with the Omicron variants, including BA 4/5, as well as other coronaviruses. This includes subjects that had previously received an mRNA-based vaccine.
• SARS-CoV-2-specific T cell responses were observed in most subjects after the second dose of VXA-CoV2-1.1-S.

"These Phase II data represent a very important milestone in the development of the world's first COVID-19 pill vaccine," said Dr. James F. Cummings, Vaxart's Chief Medical Officer, in today's press release. 

"These data also demonstrate that a pill vaccine can induce strong serum antibody responses and mucosal and T cell responses."

"Unfortunately, for the past two years, the emergence of new variants has outpaced the ability to update the currently approved injectable vaccines."

"We believe activating multiple mechanisms of the immune system that can address emerging variants may help the global community get ahead of the immunologic curve of protection."

"It could transform how we fight this and future pandemics."

Of note, Vaxart is the first company to advance an oral pill COVID-19 vaccine to Phase II clinical development.

As previously announced, Vaxart is evaluating new Omicron-based constructs as Omicron-only monovalent vaccine candidates and bivalent candidates in combination with the Company's Wuhan constructs. 

Vaxart will also compare the clinical results of its S-only and S+N constructs to determine the best path forward in developing a vaccine that can hinder viral infection and transmission for current and emerging variants. 

"The results reported today clearly indicate that the S-only construct improved antibody responses compared with the data we previously generated for the S+N construct (VXA-CoV2-1) and boosted immune responses in subjects who previously received an mRNA vaccine. These are the critical data we sought when this trial was initiated in October 2021," said Dr. Sean Tucker, Vaxart's Founder and Chief Scientific Officer.

"Additionally, the observed increase in mucosal IgA is very encouraging."

"We believe that the positive findings for multiple immunologic responses may ultimately translate to enhanced protection against infection with, and/or transmission of, SARS-CoV-2."

Vaxart believes its proprietary tablet vaccine delivery platform is suitable for delivering recombinant vaccines, positioning the company to develop oral versions of currently marketed vaccines and design recombinant vaccines for new indications. 

The company's press release was manually curated for mobile readers.