CholeraGarde®

We are developing an attenuated form of the bacterium Vibrio cholerae as a single-dose oral vaccine against cholera. In several Phase 1/2 clinical studies, single oral doses of the cholera vaccine, CholeraGarde® (or Peru-15), were administered to more than 75 human subjects and shown to be safe and immunogenic. In 1999, we announced the collaboration on a Phase 2b clinical trial of the Peru-15 vaccine with Walter Reed Army Institute of Research (WRAIR) and the National Institutes of Health (NIH). This Phase 2b trial, which began in October 2000 at Cincinnati Childrens' Hospital, tested the safety, immunogenicity and protective efficacy of the vaccine against a challenge with live virulent cholera. Results of the study demonstrated the ability of AVANT's vaccine candidate, CholeraGarde®, to provide complete protection against the trial's primary endpoint, moderate and severe diarrhea.

During 2002, AVANT completed a Phase 2 dose-ranging study with CholeraGarde®, confirming the safety and activity of this vaccine and supporting the start of trials in December 2002 with the International Vaccine Institute (IVI), supported by the Bill and Melinda Gates Foundation, in Bangladesh where cholera is endemic.

In January 2004, we announced positive preliminary results of the adult portion from the Phase 2 clinical trial of CholeraGarde® in Bangladesh. In 70 adult patients, vaccination with a single dose of CholeraGarde® was well tolerated, and over 70% of the vaccinated adults responded with a favorable immune response. In July 2005, the Bangladesh study results in children and infants showed CholeraGarde® to be well tolerated and highly immunogenic, with 77% of children aged 9 months to 5 years generating protective immune responses. Overall, these results showed the vaccine to be consistently well tolerated and immunogenic against the cholera organism in all portions of this trial.

In August 2006 AVANT announced that the International Vaccine Institute ("IVI") has received $21 million in funding from the Bill & Melinda Gates Foundation for a Cholera Vaccine Initiative (CHOVI), which will include conducting further clinical trials of CholeraGarde®. Under the direction of John D. Clemens, M.D., IVI plans to conduct Phase 2 and Phase 3 clinical trials of CholeraGarde® in Bangladesh and India beginning in 2007. IVI will be purchasing clinical materials produced at AVANT's Fall River, MA, manufacturing facility for the trials.

Selected peer-reviewed publications:

Cohen MB, Giannella RA, Bean J, Taylor DN, Parker S, Hoeper A, Wowk S, Hawkins J, Kochi SK, Schiff G, Killeen KP, 2002. Randomized, controlled human challenge study of the safety, immunogenicity, and protective efficacy of a single dose of Peru-15, a live attenuated oral cholera vaccine. Infect Immun. 70(4):1965-70.

Qadri F, Chowdhury MI, Faruque SM, Salam MA, Ahmed T, Begum YA, Saha A, Alam MS, Zaman K, Seidlein LV, Park E, Killeen KP, Mekalanos JJ, Clemens JD, Sack DA; Peru-15 Study Group, 2005. Randomized, controlled study of the safety and immunogenicity of Peru-15, a live attenuated oral vaccine candidate for cholera, in adult volunteers in Bangladesh. J Infect Dis.192(4):573-9.