BARDA Funds Development of Live Biotherapeutic Product Against C. difficile Infections

By Pavel Ryzhov, Ph.D.

Clostridiodes difficile infection (CDI) is a high-risk infectious disease, with 100,000-120,000 reported cases and 12,800 deaths each year in the US. It is considered one of the most urgent bacterial threats by the Centers for Disease Control and Prevention (CDC). However, antibiotic treatments, typical for effective management of the infection, leads to the damage of the microbiome. This results in the patients’ vulnerability to reinfection. As such, the alternative approaches for the treatment of CDI are being investigated.

For example, Vedanta Biosciences, a biopharmaceutical company that aims to develop therapies for immune system-mediated diseases, uses defined consortia of bacteria derived from the human microbiome. In the recent press release, it has announced that the Biomedical Advanced Research and Development Authority (BARDA) has awarded it with funding of $7.4 million to support an ongoing Phase 2 clinical trial [1]. The trial evaluates an orally-administered live biotherapeutic product (LBP) that contains eight commensal bacterial strains, derived from the pure, clonal bacterial cell banks. The bacterial consortium is specifically designed to promote durable and robust changes to patients’ gut microbiota. It is also produced in the powdered form and does not rely on donor fecal material with inconsistent composition.

The funding announcement comes after a previously completed Phase 1a/1b trial [2], where rapid dose-dependent bacterial colonization and improved restoration of gut microbiota were observed in healthy volunteers after treatment with antibiotics. The company also previously received a $5.4 million research grant from CARB-X and a USFDA Orphan Drug Designation in 2017 to prevent recurrent CDI.

The Phase 2 study [3] is looking to analyze the safety and efficacy of VE303 (the name for the bacterial consortium therapy) in two doses against placebo in high-risk CDI patients in a randomized, double-blind format. Specifically, patients recruited for the trial had to complete an antibiotic regimen but remain at high risk or recurrence of the infection. According to the study documents, the primary endpoint that Vedanta is looking at is the prevention of infection recurrence at eight weeks.

The BARDA award has been welcomed by Bernat Olle, Ph.D., co-founder, and CEO of Vedanta, who said that the company is “honored to be the first-ever recipient of a BARDA award in the microbiome field” and is looking forward to collaboration with the US government to “advance the clinical development of VE303 and to potentially fulfill its promise in public health and biodefense”. Notably, he remarked on the novelty of their approach to fighting this disease, where “restoration of the gut microbiota after antibiotic use is a new paradigm in infection control that could improve patient outcomes.”

BARDA’s Acting Director Gary Disbrow, Ph.D., described the purpose of the clinical study to “prevent high-risk C. difficile [infection] and reduce our dependence on antibiotics, which would be a major win for public health” and expressed enthusiasm at BARDA to support clinical development of Vedanta’s therapy. According to the agreement, Vedanta can also receive up to $69.5 million in future funding if BARDA chooses to exercise multiple options under the award.

Editor: Rajaneesh K. Gopinath, Ph.D.

Related Article: Seres Therapeutics’ Microbiome Therapy for Recurrent C. difficile Infections, Shines in Phase 3

References

1. https://www.vedantabio.com/news-media/press-releases/detail/2717/vedanta-biosciences-awarded-up-to-76-9-million-including
2. https://clinicaltrials.gov/ct2/show/NCT04236778
3. https://www.clinicaltrials.gov/ct2/show/NCT03788434

Author

Pavel Ryzhov