Vedanta Biosciences Begins Phase 3 Trial for Preventing Recurrent C. difficile Infection

Vedanta Biosciences, a clinical-stage biopharmaceutical company, has announced the dosing of the first patient in their global Phase 3 clinical trial for VE303. VE303 is designed to prevent recurrent Clostridioides difficile infection (rCDI). PureTech Health plc, the parent entity, highlighted this as a significant milestone for the VE303 program, emphasizing the potential impact of this new treatment.

The trial, named RESTORATiVE303, aims to evaluate the safety and efficacy of VE303. This study is expected to provide the necessary data for a Biologics License Application to the U.S. Food and Drug Administration (FDA). VE303 is a live biotherapeutic product candidate made up of a defined bacterial consortium. It is intended as a preventative measure for rCDI, which is a significant concern in the medical community due to its high recurrence rates and associated mortality.

Jeffrey Silber, Chief Medical Officer of Vedanta Biosciences, stated that this study marks a crucial step forward for VE303. Earlier studies have shown promising results, and this Phase 3 trial is the first of its kind to evaluate a live biotherapeutic product for preventing rCDI. Silber emphasized the potential of VE303 to offer an effective alternative to existing treatments derived from donor fecal material, which can be inconsistent.

Paul Feuerstadt from Yale University School of Medicine, another investigator for the RESTORATiVE303 study, pointed out the severe impact of CDI recurrences on patients' quality of life. He noted that the precision approach of using defined bacterial consortia represents an innovative advancement in microbiome therapeutics.

The RESTORATiVE303 trial is a randomized, double-blind, placebo-controlled study. It is being conducted at around 200 sites across 22 countries, spanning four continents. The primary measure of success will be comparing CDI recurrence rates between the VE303 and placebo groups over an eight-week period. The study design and dosing regimen are informed by the Phase 2 CONSORTIUM trial, which showed VE303 was significantly effective and well-tolerated.

VE303 consists of eight bacterial strains chosen through Vedanta's proprietary product engine. This approach ensures a standardized drug product, eliminating the variability associated with donor-derived treatments. In April 2023, the Phase 2 CONSORTIUM trial results demonstrated a 30.5% adjusted absolute risk reduction in CDI recurrence rates for those treated with a high dose of VE303 compared to placebo, translating to over an 80% reduction in recurrence odds.

Furthermore, VE303 has received Orphan Drug Designation and Fast Track Designation from the FDA for the prevention of rCDI. This recognition underscores the potential impact of VE303 in addressing a significant unmet medical need.

The development of VE303 is partly funded by a substantial contract with the U.S. Department of Health and Human Services and a research grant from the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X).

Vedanta Biosciences is focused on creating therapies for gastrointestinal diseases using defined bacterial consortia. Their lead assets, including VE303 and VE202 (for ulcerative colitis), leverage their advanced product engine capabilities. This engine is backed by extensive intellectual property and includes one of the largest libraries of human microbiome bacteria, comprehensive clinical datasets, and proprietary design and manufacturing capabilities.

PureTech Health, the parent company, is dedicated to developing transformative treatments for severe diseases. Their pipeline includes numerous therapeutics and candidates, reflecting their robust research and development framework.