A novel oral microbial therapy under development by Vedanta Biosciences reduced the risk of recurrence of Clostridioides difficile infection in a phase 2 clinical trial.
A high dose of a bacterial consortium including eight strains of commensal Clostridia prevented recurrent Clostridioides difficile infection (CDI) in a phase 2 clinical trial.
The study, published in JAMA, evaluated the safety and efficacy of VE303, a novel oral therapy being developed by Vedanta Biosciences. The results show promise for a new approach to treating recurrent CDI.
“First-generation microbiome approaches use fecal donor material of variable composition, resulting in inconsistent efficacy outcomes across different clinical studies. In contrast, the results of our VE303 phase 2 study demonstrate the potential utility of reproducible product candidates that are based on defined bacterial strains grown from clonal cell banks, in a manner analogous to monoclonal antibody production,” Jeffrey L. Silber, MD, chief medical officer of Vedanta Biosciences said in a news release.
“Our targeted approach offers consistent composition and quality attributes, which we believe could provide more consistent clinical benefit. Defined bacterial consortia also avoid the risk of pathogen transfer from donor stool— since there is no donor—and enable greater scalability compared with fecal-derived approaches.”
The study, which was designed to determine dosing for Phase 3 trials, included 79 adult participants with CDI with a median age of 63.5 years at 27 sites in the United States and Canada from February 2019 to September 2021. They were divided into three groups, with 30 participants receiving a high dose of VE303 (8.0 × 109 colony-forming units [CFUs]), 27 receiving a lo dose (1.6 × 109 CFUs) (n = 27), and 22 receiving a placebo once daily for 14 days.
Most participants (72%) received vancomycin four times daily, and 21% received fidaxomicin, which is consistent with clinical practice.
The study looked at CDI recurrence at eight weeks based on combined clinical and laboratory assessment. 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 cure through Week 24, with only two CDI recurrences reported.
The investigators also analyzed fecal microbiota of participants. Those in the high-dose group had a significantly increased detection of VE303 strains, and early colonization as 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 as well-tolerated, with no serious treatment-emergent adverse events or deaths reported.
“Vedanta’s VE303 candidate is based on compelling science that illustrates the role of gut dysbiosis in persistent inflammatory states and the potential for a rationally designed bacterial consortium to restore that balance and support healthy homeostasis of bacterial populations,” lead author Darrell Pardi, MD, chair of the division of gastroenterology and hepatology at the Mayo Clinic said in a news release.
“The notorious difficulty of preventing recurrent CDI creates a large population of patients struggling with the condition, with few therapeutic options. VE303 provides an approach that is designed to address the underlying biology in a novel way,” he continued. “The clinical data to-date have been extremely promising, and we are eager to see future updates on this program as it progresses through the clinic.”
The research was presented at the European Congress of Clinical Microbiology in Infectious Diseases (ECCMID) annual event.