Our Cholera Vaccine Candidate
Our lead product, PXVX0200, is a single-dose, oral, live, attenuated vaccine against cholera entering Phase 3 clinical trials. This vaccine is a relatively low risk, high reward product, utilizing the same strain (CVD 103-HgR) previously approved and marketed in six countries under the brand name “Orochol".
The single dose and rapid onset of protection demonstrated by CVD 103-HgR makes it ideal for travelers to cholera endemic areas. Additionally, rapid onset of protection is potentially invaluable in epidemic outbreaks where the spread of the disease needs to be controlled quickly. CVD 103-HgR was studied extensively in clinical trials, including in a field efficacy study conducted in Micronesia by the WHO1.
An initial clinical trial conducted by PaxVax with PXVX0200 has shown safety and immunogenicity. In the Phase 1 study, PXVX0200 was well tolerated and 89% of vaccine recipients seroconverted for vibriocidal antibodies vs 0% of the placebo recipients. The vaccine was well tolerated; vaccine-related solicited adverse events were infrequent and generally mild. The Phase III studies planned for licensure of PXVX0200 are being conducted in North America and Australia and will be comprised of cholera challenge, safety and immunogenicity studies.
PXVX0200 will form the basis of our traveler’s vaccine portfolio if approved for marketing within the next few years. PaxVax anticipates approval by the FDA of PXVX0200 will entitle the company to a Priority Review Voucher (PRV).
Our Avian Influenza (H5N1) Vaccine Candidate
Our second major product, PXVX0103, is an oral, live adenoviral-based vaccine against avian influenza (H5N1) or “bird flu.” This vaccine (Ad4-H5-Vtn) was evaluated in a robust ascending dosage Phase I clinical trial with over 160 subjects, who received Ad4-H5-Vtn as oral capsules. The Ad4-H5-Vtn vaccine replicated in the GI tract of the volunteers and was well tolerated at all dosages. The Ad4-H5-Vtn vaccine induced a robust cellular immune response to the H5 HA. Additionally, when the volunteers received a subsequent single intramuscular boost with H5 HA protein, they had very high rates of antibody response, with HAI seroconversion levels of up to 89%. The vaccine was well tolerated. Reactogenicity symptoms were not related to dose level; abdominal pain, nausea/vomiting and nasal congestion were more frequent in vaccinees compared to placebo, but were generally mild; none led to discontinuation of vaccine. Solicited adverse events were infrequent. This oral priming, parenteral boosting regimen (“heterologous prime-boost”) of the Ad4-H5-Vtn vaccine will be further explored in Phase II studies planned in 2014.
In addition to demonstrating proof of concept for an oral pre-pandemic vaccine, the H5N1 data demonstrates the ability of an Ad4 vector based vaccine in combination with another mode of vaccine delivery to potentially generate more robust antibody responses than traditional vaccine methodologies.
If approved, PXVX0103 will be marketed to governments for influenza pandemic defense.
Our Anthrax Vaccine Candidate
With support from the National Institute of Allergy and Infectious Diseases (NIAID), Division of Microbiology and Infectious Diseases (DMID), PaxVax is developing an oral vaccine that has the potential to significantly improve vaccine delivery and the resulting immune response in a way that could be used to protect large numbers of people. NIAID is funding current GMP production, pre-clinical studies and future Phase I studies. If milestones are met, the total award could amount to $23.8 million. An Investigational New Drug application was filed with the FDA and Phase I clinical trial was initiated in October 2013.
A single dose, oral anthrax vaccine with possibly a single protein injection would present significant advantages over the current regimen for protection against anthrax, which is comprised of five injections over 18 months. These vaccines could either be stockpiled for civilian defense by governments or by militaries that routinely vaccinate some enlisted soldiers against anthrax.
Our HIV Vaccine Candidate
With $10M of support from NIH and NIAID’s Division of Acquired Immunodeficiency Syndrome (DAIDS) and others, we are pursuing two innovative HIV vaccine candidates, both of which are based on our live, orally administered adenovirus vectors, and they are designed to be administered as a combination vaccine. The first vaccine component (Ad4-env Clade C) expresses an optimized HIV envelope protein derived from a Clade C HIV strain, and is intended primarily to induce an effective antibody response. The second vaccine component (Ad4-mGag) expresses an optimized HIV gag protein, and is intended to induce broadly reactive T cell responses. An Investigational New Drug application has been approved by the FDA and Phase I clinical trial will be initiated in 2013.
Our Dengue Vaccine Candidate
PaxVax is developing a two dose, whole virus inactivated vaccine candidate for dengue fever that encompasses all four strains of dengue fever. This vaccine candidate is currently in the pre-clinical stage and the company expects to initiate clinical trials shortly. A two dose, inactivated vaccine for dengue, like those for other flaviviruses (Japanese encephalitis and tick borne encephalitis) would likely be administered over a short period of time and be an attractive vaccine for travelers and for controlling outbreaks. The leading vaccine in development for dengue comprises of three doses over one year and may not be as convenient for travelers.
PaxVax anticipates approval of the vaccine by the FDA will entitle the company to a Priority Review Voucher (PRV).
1. Calain P, Chaine JP, Johnson E, Hawley ML, O'Leary MJ, Oshitani H, Chaignat CL. Can oral cholera vaccination play a role in controlling a cholera outbreak? WHO Western Pacific Regional Office, Manila, Philippines. Retreived from http://www.ncbi.nlm.nih.gov/pubmed/15193408