Oral Bacterial Therapy for Recurrent CDI Shows Promise in Phase 2 Trials

A high-dose bacterial consortium containing eight commensal Clostridium strains prevented relapse Clostridioides difficile Infectious disease (CDI) in a phase 2 clinical trial.

Research published in jamevaluated the safety and efficacy of VE303, a novel oral therapy being developed by Vedanta Biosciences. This result indicates the potential of a new approach to treat recurrent CDI.

“First-generation microbiome approaches use faecal donor materials of varying composition, resulting in inconsistent efficacy results across clinical studies. In contrast, our VE303 Phase 2 study These results demonstrate the potential utility of reproducible product candidates based on specific bacterial strains grown from clonal cell banks in a manner similar to monoclonal antibody production,” Jeffrey L. Silber, MD. , Chief Medical Officer of Vedanta Biosciences said: news release.

“We believe our targeted approach can provide consistent composition and quality attributes and deliver more consistent clinical benefits. It avoids the risk of pathogen transfer from donor stool and allows greater scalability compared to fecal-derived approaches.”

Designed to determine dose for a Phase 3 trial, the study included 79 people 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. of adult participants were included. They were divided into her three groups. Thirty participants received a high dose of her VE303 (8.0 × 109 colony forming units). [CFUs]), 27 received the lo dose (1.6 × 109 CFU) (n = 27) and 22 received placebo once daily for 14 days.

Most participants (72%) received vancomycin four times daily and 21% received fidaxomicin consistent with clinical practice.

This study examined CDI recurrence at 8 weeks based on a combination of clinical and laboratory assessments. Recurrent CDI was reported in 13.8% of participants in the high-dose group, 37% in the low-dose group and 45.5% in the placebo group. All recurrences occurred by his 11th day in the high-dose group.

Most participants experienced sustained healing by week 24, with only two reported CDI relapses.

Investigators also analyzed the faecal microbiota of the participants. Patients in the high-dose group had significantly increased detection of the VE303 strain, and early colonization was associated with greater therapeutic efficacy. Microbial diversity was restored most significantly in the high-dose group.

The adjusted absolute risk reduction was 30.5% in the high-dose group compared with other treatment options such as fecal microbial transplantation (28%), bezlotoxumab (10%) and RBX2660 (12.3%).

The treatment was well tolerated and no serious treatment-related adverse events or deaths were reported.

“Vedanta’s VE303 candidate demonstrates the role of the gut microbiota in persistent inflammatory conditions and the potential for rationally-designed bacterial consortia to restore its balance and support healthy homeostasis of bacterial populations. It’s based on compelling science,” said lead author Darrell Pardi, MD, chair of the Department of Gastroenterology and Hepatology at the Mayo Clinic, in a news release.

“The notorious difficulty of preventing recurrence of CDI has created a large number of patients suffering from a condition with few treatment options. We offer an engineered approach,” he continued. “The clinical data to date are very encouraging and we look forward to future updates to this program as it progresses in our clinics.”

This study was presented at the annual event of the European Conference on Clinical Microbiology of Infectious Diseases (ECCMID).