Vedanta Biosciences, a clinical-stage company that is developing a potential new category of oral therapies based on defined bacterial consortia, today announced the publication of Phase 2 study results from its lead program, VE303, in the Journal of the American Medical Association (JAMA), as well as a late-breaker oral presentation at the European Congress of Clinical Microbiology in Infectious Diseases (ECCMID) annual event.
The publication includes analyses of safety, efficacy, in preventing recurrence of Clostridioides difficile infection (rCDI), and VE303 strain colonization data from the successfully completed Phase 2 study of VE303. The ECCMID presentation offers more in-depth scrutiny of VE303 strain colonization dynamics and its relationship to the observed clinical effect. Colonization dynamics is analogous to traditional drug pharmacokinetics and refers to the growth and persistence over time of bacterial strain populations in the human gut.
“First-generation microbiome approaches use fecal donor material of variable composition, resulting in inconsistent efficacy outcomes across different clinical studies. In contrast, the results of our VE303 Phase 2 study demonstrate the potential utility of reproducible product candidates that are based on defined bacterial strains grown from clonal cell banks, in a manner analogous to monoclonal antibody production,”
said Jeffrey L. Silber, M.D., Chief Medical Officer of Vedanta.
“Our targeted approach offers consistent composition and quality attributes, which we believe could provide more consistent clinical benefit. Defined bacterial consortia also avoid the risk of pathogen transfer from donor stool—since there is no donor—and enable greater scalability compared with fecal-derived approaches.”
“Vedanta’s VE303 candidate is based on compelling science that illustrates the role of gut dysbiosis in persistent inflammatory states and the potential for a rationally designed bacterial consortium to restore that balance and support healthy homeostasis of bacterial populations,”
said Darrell Pardi, M.D., Chair of the Division of Gastroenterology and Hepatology at the Mayo Clinic in Rochester, Minnesota, and senior author of the JAMA paper.
“The notorious difficulty of preventing recurrent CDI creates a large population of patients struggling with the condition, with few therapeutic options. VE303 provides an approach that is designed to address the underlying biology in a novel way. The clinical data to-date have been extremely promising, and we are eager to see future updates on this program as it progresses through the clinic.”
The Journal of the American Medical Association Publication
The JAMA paper, “VE303, a Defined Bacterial Consortium, vs. Placebo for the Prevention of Recurrent Clostridioides difficile Infection: A Randomized Trial,” expands on the results of the Phase 2 study of VE303, which was designed to identify the recommended dose for a Phase 3 study of VE303. The study data confirmed that VE303 prevented recurrent CDI compared with placebo in the study population. The publication announced today includes new analyses of secondary efficacy endpoints, such as CDI recurrence rates at week 24, and stool microbiome endpoints, which included both VE303 strain colonization and gut microbiome diversity.
VE303 is a defined bacterial consortium therapeutic candidate designed for the prevention of recurrent Clostridioides difficile infection (rCDI). It consists of eight strains that were rationally selected using Vedanta’s discovery engine. VE303 is produced from pure, clonal bacterial cell banks, which yield a standardized drug product in powdered form and bypass the need to rely on direct sourcing of donor fecal material of inconsistent composition. Vedanta reported positive topline results in October 2021 from the Phase 2 CONSORTIUM trial, in which VE303 was associated with a 31.7% absolute risk reduction in the rate of recurrence when compared with placebo, representing a greater than 80% reduction in the odds of a CDI recurrence. Vedanta believes VE303 has the potential to become a first-in-class therapeutic based on a defined bacterial consortium. Vedanta Biosciences received a $5.4 million research grant from the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) in 2017 and a contract of up to $81.9 million from Biomedical Advanced Research and Development Authority (BARDA) in 2020 to support clinical studies of VE303. VE303 was granted Orphan Drug Designation in 2017 by the U.S. Food and Drug Administration (FDA) for the prevention of recurrent CDI.