PaxVax Inc, which develops and commercializes innovative vaccines against infectious diseases in a socially responsible manner, today announced that it has commenced its Phase 3 clinical trial program for its single-dose oral cholera vaccine candidate, PXVX0200 (also known as CVD 103-HgR). Approximately 3,000 participants will be enrolled in this pivotal program, which is comprised of cholera challenge, safety, and immunogenicity studies.
“We are proud and excited to develop the first potential oral, single-dose, and fast-acting cholera vaccine for travelers in the U.S. and around the world”
Cholera is an acute intestinal 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. No vaccine for cholera is currently available in the United States (U.S.) for residents who may travel abroad to areas where cholera is common. A cholera vaccine is available in Europe and elsewhere for travelers, but it requires a two-dose regimen, which takes longer to complete. A single-dose, oral vaccine would be more convenient for all travelers to take, particularly for those traveling on short notice.
The pivotal efficacy cholera challenge studies will be randomized, double-blind, placebo-controlled, and conducted at three top vaccine testing centers, including the University of Maryland, the University of Vermont Vaccine Testing Center, and Cincinnati Children's Hospital Medical Center. Volunteers enrolled in these studies will first be vaccinated and then challenged, or exposed to the cholera-causing agent (Vibrio cholerae bacterium). At 10 days following vaccination, and again at three months post vaccination, participants will be evaluated to determine the protective ability of PXVX0200. All standard clinical trial safety protocols and guidelines will be followed at each clinical research center. Additional trials will also be conducted at sites in Canada, Australia, and the U.S. to confirm vaccine safety in a larger population, measure immunogenicity, and demonstrate lot-to-lot consistency of different vaccine manufacturing batches required by the U.S. Food and Drug Administration (FDA).
In recognition of the lack of any available traveler's vaccine against cholera, and the corresponding unmet medical need, PXVX0200 has been granted Fast Track designation by FDA.
Positive results from the Phase 1 trial showed that a single oral dose of PXVX0200 was highly immunogenic; overall, seroconversion to 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 name "Orochol."
"Cholera continues to infect areas around the world that suffer from poor sanitation, poverty, and poor access to safe drinking water, particularly parts of the world like Haiti and South Asia that are recovering from recent natural disasters," said Mitch Cohen, M.D., Professor and Vice Chair of Pediatrics for Clinical Affairs at Cincinnati Children's Hospital Medical Center. "For travelers visiting endemic areas of the world, where significant risk of contracting cholera exists, we are eager to start these clinical trials, which will determine if an oral, single dose of PXVX0200 provides protection against cholera after vaccination."
FDA approval of PXVX0200 may entitle PaxVax to receive a Priority Review Voucher. This government incentive, given for FDA approval of a therapy or vaccine against a neglected tropical disease, grants the recipient priority review for another product that would not otherwise receive it, and has a potential market value of $50 million to $300 million. Since the program's inception in 2007, FDA has granted two Priority Review Vouchers, one of which was redeemed.
"We are proud and excited to develop the first potential oral, single-dose, and fast-acting cholera vaccine for travelers in the U.S. and around the world," said Ken Kelley, Chief Executive Officer of PaxVax. "PXVX0200 is our lead vaccine candidate. Pending the successful outcome of these trials, we hope to file a Biologics License Application (BLA) and begin to establish our traveler's vaccine portfolio."