Topline Findings
- VE202 Phase II Results: Vedanta Biosciences’ VE202 did not meet the trial’s primary endpoints treating mild-to-moderate ulcerative colitis (UC), highlighting ongoing challenges for microbiome-based therapies.
- Pipeline Advancement: Vedanta is moving forward with the Phase III RESTORATiVE303 trial for VE303 in preventing recurrent C. difficile infection and advancing VE707 to combat multidrug-resistant infections.
- UC Overview: UC affects an estimated one million people in the United States, is more common in white populations, slightly more common in women, and presents a bimodal age distribution, underscoring a significant unmet medical need.
Results from the Phase II COLLECTiVE202 trial (NCT05370885) showed that Vedanta Biosciences’ VE202 failed to demonstrate any statistically significant differences compared to placebo in patients with mild-to-moderate ulcerative colitis (UC). According to the company, the outcome is a setback for microbiome-based approaches in inflammatory bowel disease, but the findings will help inform future research directions and guide the development of next-generation therapies.1
What’s Next for Vedanta After VE202’s Phase II Setback?
“We are very disappointed that our study did not meet its efficacy endpoints, and our greatest regret is that people living with inflammatory bowel disease will not, for now, have the opportunity to benefit from a new treatment option,” said Bernat Olle, PhD, CEO, Vedanta Biosciences, in a press release. “The gut microbiome is a well-recognized driver of IBD, yet remains a facet of the disease untouched by current treatments. As a field, we have not yet succeeded in making a meaningful impact for people with IBD through microbiome-based approaches, but every study moves us closer to that goal. We are committed to sharing further analyses of this study at upcoming scientific meetings to help chart new paths forward.”
Key Details of the COLLECTiVE202 Trial
- The double-blind, placebo-controlled, randomized COLLECTiVE202 trial evaluated the safety, efficacy, and microbiota changes of VE202 in 114 patients with mild-to-moderate UC who did not have prior exposure to any biologic or advanced oral therapies.
- Patients were randomly assigned to receive either VE202 or placebo.
- The dual primary endpoints of the trial were safety and endoscopic response by week eight.
- Key secondary endpoints included clinical response and remission, endoscopic improvement and remission, histological assessments and measures of colonization, quality-of-life, and inflammatory biomarkers.1,2
- Despite failing to meet both primary endpoints, VE202 was reported to be safe and well tolerated.
- Most adverse events (AEs) were reported to be mild to moderate in intensity. There were no know treatment-related AEs.
- Analyses of bacterial colonization, histological findings, and immune responses are in progress, with results expected at upcoming scientific forums.
Vedanta’s Pipeline Focus
- Moving forward, Vedanta is prioritizing the advancement of its broader pipeline, including the global Phase III RESTORATiVE303 trial of VE303 for preventing recurrent C. difficile infection, now enrolling patients across more than 200 sites in 24 countries.
- This program builds on strong Phase II results, in which VE303 delivered what the company described as potentially best-in-disease efficacy.
- Vedanta is also progressing VE707, aimed at preventing infections caused by multidrug-resistant organisms in vulnerable patient populations, with an Investigational New Drug submission targeted for the first half of 2026.1
UC Prevalence and Demographics
- According to Medscape, an estimated one million people are currently living with UC in the United States.
- The estimated prevalence is 35 to 100 cases out of every 100,000 people.
- UC is three times more common than Crohn disease.
- UC is notably more common in white individuals than in Black or Hispanic populations, with some reports suggesting a two- to fourfold higher incidence in Ashkenazi Jews, though North American data do not fully confirm this.
- The disease is slightly more prevalent in women and typically presents in a bimodal age pattern, peaking between the ages of 15 and 25 years, and again between the ages of 55 and 65 years, but it can develop at any age.3
Vedanta’s Ongoing Focus on VE303
“Our priority at Vedanta remains the successful execution of our ongoing global pivotal study of VE303 for the prevention of recurrent C. difficile infection, with the goal of potentially delivering the first approved Live Biotherapeutic Product in any indication—and, in doing so, addressing a serious health condition with a significant unmet medical need,” concluded Ollie, in the press release.
References
- Vedanta Biosciences Announces Phase 2 Study of VE202 in Ulcerative Colitis Did Not Meet Primary Endpoint. BusinessWire. August 13, 2025. Accessed August 14, 2025. https://www.businesswire.com/news/home/20250813508109/en/Vedanta-Biosciences-Announces-Phase-2-Study-of-VE202-in-Ulcerative-Colitis-Did-Not-Meet-Primary-Endpoint
- VE202 in Patients With Mild-to-Moderate Ulcerative Colitis. Clinicaltrials.gov. Accessed August 14, 2025. https://clinicaltrials.gov/study/NCT05370885?term=NCT05370885&rank=1
- Ulcerative Colitis. Medscape. Accessed August 14, 2025. https://emedicine.medscape.com/article/183084-overview#a6
