SUMMIT ANNOUNCES POSITIVE TOP-LINE DATA FROM AN EXPLORATORY PHASE 2 CLINICAL TRIAL SUPPORTING RIDINILAZOLE AS A HIGHLY SELECTIVE ANTIBIOTIC FOR THE TREATMENT OF CDI
Ridinilazole treatment more preserving of gut microbiome than fidaxomicin
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Oxford, UK, 5 September 2017 – Summit Therapeutics plc (NASDAQ: SMMT, AIM: SUMM), the drug discovery and development company advancing therapies for Duchenne muscular dystrophy and Clostridium difficile infection (‘CDI’), today announces positive top-line data from an exploratory Phase 2 clinical trial that support ridinilazole as a highly selective and potent antibiotic product candidate for the treatment of CDI. In the Phase 2 clinical trial, ridinilazole preserved the gut microbiome of CDI patients to a greater extent than the marketed narrow-spectrum antibiotic, fidaxomicin. During the trial’s ten-day treatment period, ridinilazole treatment had markedly less impact on the gut microbiome of trial patients by measures of overall diversity and changes in key bacterial families, when compared to those trial patients dosed with fidaxomicin.
In the trial, ridinilazole and fidaxomicin both reduced the abundance of C. difficile. However, fidaxomicin-treated patients had reduced abundancy of other bacterial families associated with microbiome health. For a number of these bacterial families, the difference between the two treatments was statistically significant. Another measure of microbiome health is alpha diversity as measured by the Simpson’s Diversity Index. There was a greater reduction in alpha-diversity during fidaxomicin treatment compared with ridinilazole-treated patients. These measures were a key secondary endpoint of the clinical trial and provide additional evidence of ridinilazole’s precision in killing C. difficile while preserving the gut microbiome. The primary endpoint of the trial was safety, as measured by the number of treatment emergent adverse events and serious adverse events. During the trial, no new or unexpected safety signals were identified and ridinilazole was well-tolerated.
“We increasingly recognise the importance of a healthy and diverse gut microbiome for protection against recurrent CDI, which is a major challenge in the management of the disease. These latest clinical findings show ridinilazole better preserved the microbiome of CDI patients than fidaxomicin, the narrowest spectrum antibiotic currently available for CDI,” commented Professor Mark Wilcox, Consultant Microbiologist & Head of Microbiology Research & Development at the Leeds Teaching Hospitals NHS Trust, Professor of Medical Microbiology at the University of Leeds, and Public Health England’s Lead on C. difficile in England. “Further, these microbiome data are very supportive of ridinilazole’s profile as a highly selective antibiotic with the potential to achieve a meaningful improvement in clinical outcomes for CDI patients.”
The exploratory open-label Phase 2 clinical trial enrolled 27 patients aged between 18 and 90 years at trial sites in the US, the UK and the Czech Republic. Patients were randomly assigned to receive either ridinilazole (200mg, twice a day) or fidaxomicin (200mg, twice a day) for ten days. The trial population was unbalanced with more patients randomised to ridinilazole at higher risk of poorer clinical outcomes as measured by ATLAS score, and also with predisposing factors for recurrent CDI.
A secondary endpoint of sustained clinical response (‘SCR’), defined as clinical cure at the end of treatment and no recurrence of CDI within the next 30 days, was achieved in seven of 14 ridinilazole treated patients and six of 13 fidaxomicin treated patients. The trial was not designed for efficacy comparisons due to the small number of patients.
Dr David Roblin, Chief Medical and Operating Officer of Summit added, “Ridinilazole is a precision antibiotic that is designed to selectively target C. difficile while being highly preserving of the gut microbiome that plays a crucial role in naturally protecting against recurrent CDI. Ridinilazole has now provided evidence of its high selectivity in two complementary clinical trials. The data from our earlier Phase 2 trial showed a greater microbiome preservation of ridinilazole-treated patients compared with the current standard of care, vancomycin, which led to achieving statistical superiority in sustained clinical response. We believe ridinilazole has the potential to become a front-line therapy for CDI and look forward to initiating Phase 3 clinical trials in the first half of 2018.”
More detailed findings from this trial are expected to be presented at an upcoming international infectious disease conference. The results build on positive data from a Phase 2 proof of concept trial of ridinilazole that were published in The Lancet Infectious Diseases in April 2017. Ridinilazole is currently being prepared for Phase 3 clinical trials that are planned to commence in the first half of 2018.