In findings published this week, the investigational therapy, VE303, which is being developed for recurrent Clostridioides difficile infection (rCDI) demonstrated it was able to reduce the chance of recurrence by more than 80% compared to placebo in its phase 2 CONSORTIUM study.1
“Due to VE303’s precisely known, defined composition, we can study its mechanisms of action and PK-PD relationships in a rigorous way, taking a step towards understanding why some patients respond better than others to a microbiome restoration intervention,” said Vedanta Biosciences CEO Bernat Olle, PhD, in a statement. “We believe this line of work helps fill a knowledge gap in the field, since characterization of the mechanisms of action of first-generation fecal microbiota products has been very limited.”2
The investigators also write prevention of rCDI comes through multiple mechanisms.
What You Need to Know
VE303, a defined bacterial consortium developed for recurrent Clostridioides difficile infection (rCDI), demonstrated over an 80% reduction in recurrence odds compared to placebo in the phase 2 CONSORTIUM study.
VE303’s precisely defined composition allows for detailed studies on its mechanisms of action, particularly its PK-PD relationships. This approach advances understanding of why some patients respond better to microbiome restoration therapies, addressing gaps left by earlier, less characterized fecal microbiota products.
VE303 showed robust colonization in high-dose groups, correlating with non-recurrence. Multi-omic analyses identified critical predictors of success, such as antibiotic history, baseline stool metabolites, and serum cytokines.
“VE303 organisms robustly colonized the gut in the high-dose group and were among the top taxa associated with non-recurrence. Multi-omic modeling identified antibiotic history, baseline stool metabolites and serum cytokines as predictors of both on-study CDI recurrence and VE303 colonization. VE303 potentiated early recovery of the host microbiome and metabolites with increases in short-chain fatty acids, secondary bile acids and bile salt hydrolase genes after antibiotic treatment for CDI, which is considered important to prevent CDI recurrences,” they wrote.1
Read more:Updated Details on Vedanta's Phase 3 VE303 Trial for Recurrent C difficile
Based on a previous report by Contagion, in the phase 2 trial CDI recurrence was reported among 13.8% of participants in the high-dose group, 37% in the low-dose group, and 45.5% in the placebo group. In the high-dose group, all recurrences occurred by Day 11. Most participants experienced sustained cures through Week 24, with only 2 CDI recurrences reported. The investigators also analyzed the fecal microbiota of participants. Those in the high-dose group had a significantly increased detection of VE303 strains, and early colonization was associated with greater treatment efficacy. Microbial diversity recovered most notably in the high-dose group. The adjusted absolute risk reduction was 30.5% in the high-dose group, compared with other treatment options, including fecal microbial transplant (28%), bezlotoxumab (10%), and RBX2660 (12.3%). The treatment was well-tolerated, with no serious treatment-emergent adverse events or deaths reported.
VE303 is a potential first-in-class live biotherapeutic product for the prevention of rCDI. It is an orally administered, defined bacterial consortium therapeutic candidate which consists of 8 strains that were rationally selected using Vedanta’s product 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.2
Results from the phase 2 study informed the design and dose selection for the global phase 3 study, RESTORATiVE303, that is currently underway to confirm the efficacy and safety profile of VE303 in the prevention of rCDI. Topline data for this study are expected in 2026.2
References
1. Menon, R., Bhattarai, S.K., Crossette, E. et al. Multi-omic profiling a defined bacterial consortium for treatment of recurrent Clostridioides difficile infection. Nat Med 31, 223–234 (2025). https://doi.org/10.1038/s41591-024-03337-4
2.Vedanta Biosciences Publishes Additional Phase 2 VE303 Results in Nature Medicine. Vedanta press release. January 23, 2025. Accessed January 24, 2025. https://www.businesswire.com/news/home/20250123611854/en/Vedanta-Biosciences-Publishes-Additional-Phase-2-VE303-Results-in-Nature-Medicine
