Vedanta's microbiome therapy for IBD disappoints

While Vedanta Biosciences waits for a phase 3 readout for its lead microbiome therapy based on live bacteria, an earlier-stage programme has failed a mid-stage trial.

The Cambridge, Massachusetts-based biotech revealed that its phase 2 COLLECTiVE202 trial of VE202 in people living with ulcerative colitis, a form of inflammatory bowel disease (IBD), did not meet its main efficacy objective.

VE202, an orally administered mix of 16 different bacterial strains designed to repopulate the lower gastrointestinal tract and restore a healthy balance to the gut microbiome, was unable to reduce disease severity – measured using the Mayo endoscopic response subscore – compared to placebo in the trial.

COLLECTiVE202 enrolled 114 patients, between the ages of 18 and 75 years, with mild-to-moderate ulcerative colitis who had not been exposed to any biologic or advanced oral therapies. There was no update on secondary endpoints in the study, which included clinical response and remission, endoscopic improvement and remission, and histological assessments.

Still, Vedanta confirmed it is now focusing its attention on VE303, currently in the phase 3 RESTORATiVE303 trial for the prevention of recurrent Clostridium difficile infections (rCDI), and VE707, a microbiome therapy designed to prevent infections by multidrug-resistant (MDR) organisms that should start clinical testing next year.

"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 Vedanta's chief executive, Bernat Olle, in a statement.

"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," he added.

In a social media post, Olle also revealed that Vedanta will be reducing its headcount by 20% as a direct result of the failed trial.

"Drug development rarely follows a straight path," he wrote. "You can do the right science, run the right study, and still be humbled by the complexities of human biology."

RESTORATiVE303 is due to generate results in 2027, according to the clinicaltrials.gov registry. If the results are positive, VE303 could become an option for a potentially serious infection that causes around 500,000 illnesses and between 15,000 and 30,000 deaths annually in the US.

The standardised formulation is being positioned as a safer, more consistent alternative to faecal transplants, which involve taking stool from a healthy donor and putting it in the colon of a person infected with C difficile.

Vedanta is playing catch-up with VE303, however, as a rival microbiome therapy from Seres Therapeutics, called Vowst, has been approved as an rCDI option since 2023. Nestlé Health Science, which commercialised Vowst on behalf of Seres after launch, acquired worldwide rights to the product last year.

Image by Darko Djurin from Pixabay