Summit Announces Publication of Phase 2 Clinical Analyses of Gut Microbiome Health
July 13, 2020 – Summit Therapeutics plc announced the publication of data from the Phase 2 clinical trial of the company’s precision antibiotic, ridinilazole, in development for the treatment of C. difficile infection (‘CDI’) in the American Journal of Physiology – Gastrointestinal and Liver Physiology. The data published in collaboration with researchers at Tufts University and Tufts Medical Center demonstrated that ridinilazole’s microbiome preservation resulted in a gut environment expected to inhibit the growth of C. difficile. In contrast, vancomycin treatment resulted in a gut environment that may more highly favor the growth of C. difficile. The difference in gut environment could explain the approximately 60% relative reduction in recurrence observed in patients treated with ridinilazole over vancomycin in the Phase 2 trial.
“This is the first scientific article ever to show the effect of antibiotics treating CDI on the bile acid composition in the human gut. In addition, CoDIFy is the first clinical study to highlight the differential effects of antibiotics on bile acids, which are known to create environments that can either promote or protect against CDI,” said Dr. Ventzislav Stefanov, Executive Vice President and President of Discuva. “The protective gut environment observed after ridinilazole treatment, compared to vancomycin, provides a strong rationale for the higher sustained clinical response observed in patients taking ridinilazole in the CoDIFy clinical trial.”
The Phase 2 clinical trial enrolled 100 patients, half of whom received ridinilazole and the other half vancomycin. The publication, “Ridinilazole, a narrow spectrum antibiotic for treatment of Clostridioides difficile infection, enhances preservation of microbiota-dependent bile acids,” was authored by X. Qian, K. Yanagi, A. Kane, N. Alden, M. Lei, D. Snydman, R. Vickers, K. Lee and C. Thorpe. In the published data, there was a higher ratio of pro-C. difficile to anti C.-difficile bile acids at the start of treatment for both ridinilazole- and vancomycin-treated patients. This was expected, as patients who get CDI have perturbed microbiomes. However, during treatment, patients treated with vancomycin showed a further decrease in anti-C. difficile bile acids and had stools dominated by pro-C. difficile bile acids. In contrast, this did not occur in ridinilazole-treated patients. By the end of the study period, ridinilazole-treated patients’ bile acid ratios trended towards a healthy, non-CDI state. These results support the data from the Phase 2 clinical trial, in which patients receiving ridinilazole showed a statistically significant improvement in sustained clinical responses.