Vedanta Biosciences Begins Phase 3 Study of VE303 for Preventing Recurrent C. difficile Infection

Vedanta Biosciences, a clinical-stage biopharmaceutical company, has initiated the global Phase 3 RESTORATiVE303 clinical trial by dosing its first patient. This trial is designed to evaluate VE303, an orally administered, defined bacterial consortium aimed at preventing recurrent Clostridioides difficile infection (rCDI). The study will form the basis for a Biologics License Application (BLA) to be submitted to the U.S. Food and Drug Administration (FDA).

According to Jeffrey Silber, M.D., the Chief Medical Officer at Vedanta Biosciences, the commencement of the RESTORATiVE303 study signifies a pivotal clinical milestone for the VE303 program. He highlighted the importance of this study by stating, "RESTORATiVE303 is the first pivotal Phase 3 study of a live biotherapeutic product aimed at preventing recurrent CDI." Silber also emphasized the severe impact of CDI, which affects up to 175,000 patients and causes approximately 20,000 deaths annually in the U.S. He expressed confidence in VE303's potential, suggesting it could offer a viable alternative to current undefined donor-derived fecal approaches.

Vedanta Biosciences had previously published results from the Phase 2 CONSORTIUM trial in April 2023, which demonstrated a 30.5% adjusted absolute risk reduction in CDI recurrence with VE303 compared to placebo. This equates to over an 80% reduction in the odds of recurrence.

Paul Feuerstadt, M.D., a study investigator from Yale University School of Medicine, pointed out that CDI can recur in over 25% of those infected, often repeatedly, despite initial antibiotic success. Each recurrence can severely diminish the quality of life, leading to hospitalization and increased mortality risk. Feuerstadt emphasized the significance of precision approaches using defined bacterial consortia, lauding the opportunity to participate in this groundbreaking Phase 3 study.

The RESTORATiVE303 trial is a randomized, double-blind, placebo-controlled Phase 3 clinical study, evaluating the safety and efficacy of VE303 in patients at high risk for CDI recurrence. The trial spans around 200 sites across 22 countries and four continents. Its primary endpoint is the comparison of CDI recurrence rates at eight weeks between the VE303 and placebo groups. The Phase 3 study builds on the completed Phase 2 trial, which showed VE303's effectiveness in preventing CDI recurrences at eight weeks and its general tolerability.

VE303 is a potential first-in-class live biotherapeutic product (LBP) designed to prevent recurrent CDI. Comprising eight bacterial strains, VE303 is produced from pure, clonal bacterial cell banks, ensuring a standardized powdered drug product. This approach eliminates the need for donor fecal material, which can be inconsistent in composition. The Phase 2 CONSORTIUM trial demonstrated significant efficacy of VE303 in reducing CDI recurrence rates. The U.S. FDA granted Orphan Drug Designation to VE303 in 2017 and Fast Track Designation in 2023 for the prevention of recurrent CDI.

Vedanta Biosciences has received significant funding for this project, including federal funds from the U.S. Department of Health and Human Services' Biomedical Advanced Research and Development Authority, totaling up to $104.2 million. In 2017, the project also received a $5.4 million research grant from the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X).

Vedanta Biosciences specializes in developing therapies for gastrointestinal diseases. Its leading assets include VE303, currently in a Phase 3 trial for rCDI prevention, and VE202, in a Phase 2 trial for treating ulcerative colitis. The company's product engine, supported by a broad intellectual property portfolio, features one of the largest collections of human microbiome bacteria, extensive clinical data, proprietary consortium design capabilities, and end-to-end CGMP manufacturing for commercial-scale production.