PaxVax Inc, which develops and commercializes innovative vaccines against infectious diseases in a socially responsible manner, today announced interim data from a Phase 3 cholera challenge study of its single-dose oral cholera vaccine candidate, PXVX0200 (also known as CVD 103-HgR). Trial investigators compared the rate of diarrhea in participants vaccinated with PXVX0200 to the rate in participants who had received placebo. The vaccine appeared well tolerated. In an interim analysis of participants challenged at 10 days post vaccination with wild type, fully pathogenic cholera bacteria the rate of diarrhea was reduced in the vaccine group: 20 of 33 participants who received placebo experienced moderate-to-severe diarrhea compared to two of 35 participants who received PXVX0200.
Vaccine efficacy is evaluated when volunteer participants are immunized with an oral dose of the PXVX0200 vaccine or placebo and are then subsequently exposed to the cholera-causing agent (Vibrio cholerae O1 El Tor). Volunteer participants in this challenge study were divided into two groups - the first group was vaccinated and then challenged at 10 days after vaccination. As part of the study design, a second, separate group of volunteer participants will be challenged at 90 days post vaccination to further evaluate duration of vaccine protection. Final study results will be reported as a "co-primary endpoint", which will combine both challenge time points at 10 and 90 days after vaccination.
Cholera is an acute intestinal diarrheal infection caused by toxigenic Vibrio cholerae bacteria generally acquired by ingesting contaminated water or food. According to the World Health Organization, the global disease burden is estimated to be three to five million cases and 100,000 to 130,000 deaths per year. Cholera often manifests as explosive epidemics that rapidly move through populations, such as the outbreaks that occurred in Peru and Haiti in 1991 and 2010, respectively.
This pivotal efficacy cholera challenge study is a randomized, double-blind, placebo-controlled trial underway at three top vaccine testing centers: the Center for Vaccine Development of the University of Maryland School of Medicine, the University of Vermont Vaccine Testing Center, and Cincinnati Children's Hospital Medical Center.
Wilbur Chen, M.D., M.S., Assistant Professor at the University of Maryland School of Medicine, Center for Vaccine Development and Primary Investigator commented on the study: "Interim results are highly encouraging and justify continuing the study to evaluate protection from cholera challenge 90 days post vaccination, as well as proceeding with the additional planned studies of safety, immunogenicity, and lot-to-lot consistency of this cholera vaccine".
A vaccine for cholera is not currently available for U.S. residents who travel abroad to areas where cholera poses a risk (e.g., Haiti). A cholera vaccine is available in Europe and elsewhere for travelers, but it requires a two-dose regimen. If licensed, the single-dose, oral PXVX0200 vaccine would be more convenient for all travelers, particularly for those traveling on short notice.
In addition to the 10-day and 90-day cholera challenge studies, immunogenicity, safety, and lot consistency of the PXVX0200 cholera vaccine will be evaluated in a broader population at trial sites in Canada, Australia, and the U.S. Approximately 3,000 participants will be enrolled in these additional pivotal Phase 3 clinical studies.
"As a result of favorable data reported from the 10-day challenge component we will continue with the Phase 3 program, and look forward to additional positive results that will provide the evidence-base to support a Biologics License Application for PXVX0200, our lead vaccine candidate," said Ken Kelley, Chief Executive Officer of PaxVax. "We are excited about the prevailing opportunity to protect U.S. travelers from cholera, and also believe that PXVX0200 may allow us to bring a logistically simple, single-dose cholera vaccine to developing countries for use during explosive cholera outbreaks."
Positive results from the previous Phase 1 trial showed that a single oral dose of PXVX0200 was highly immunogenic; overall, seroconversion of vibriocidal antibody occurred in 89 percent of vaccinees by day 14. Onset of immune response induced by the vaccine was also rapid with 80 percent of subjects demonstrating seroconversion by 10 days after administration. The vaccine was well tolerated; adverse events were infrequent and generally mild and comparable to placebo. PXVX0200 is the same attenuated vaccine strain (CVD 103-HgR) that was previously approved and marketed in several countries under the brand names "Orochol" and "Mutacol."