Oxford, UK, 24 February 2016 - Summit Therapeutics plc (NASDAQ: SMMT, AIM: SUMM), the drug discovery and development company advancing therapies for Duchenne muscular dystrophy and Clostridium difficile infection (‘CDI’), announces the online publication of preclinical data in the Journal of Antimicrobial Chemotherapy supporting ridinilazole as a novel and potent antibiotic against CDI. The peer-reviewed paper reports ridinilazole outperformed the current standards of care, vancomycin and metronidazole, in preclinical studies by having a robust killing effect on C. difficile that significantly reduced the level of toxins produced by the bacteria that play a major role in driving the symptoms and severity of the disease. The study, funded by Summit, was conducted as part of a collaboration with researchers at the University of Houston College of Pharmacy.
“Ridinilazole is truly a differentiated antibiotic, driven by its exquisite selectivity and potency against C. difficile in preclinical studies, with the potential to treat CDI and reduce recurrent disease,” commented Kevin W. Garey, PharmD, MS, FASHP, Chair, Department of Pharmacy Practice and Translational Research Professor of Pharmacy Practice at the University of Houston College of Pharmacy and Principal Investigator in the study. “The data presented in this paper highlight some of ridinilazole’s potential advantages over the current standard of care antibiotics for CDI in the key virulence factor, toxin production. Based on all of the preclinical and recent positive Phase 2 clinical data, I believe ridinilazole has a promising future in the treatment of CDI.”
The research was published in the paper entitled, “Impact on toxin production and cell morphology in Clostridium difficile by ridinilazole (SMT19969), a novel treatment for C. difficile infection.” Progression of CDI most commonly involves production of toxin A and B by C. difficile to elicit an inflammatory response, including IL-8 release, which results in symptoms of disease including severe diarrhoea. In the study, in vitro treatment of C. difficile isolates with ridinilazole resulted in a significant reduction in toxin A and B levels and subsequent IL-8 release. These data were in contrast to treatment with vancomycin and metronidazole that were both comparable to control. Insights into the mechanism of ridinilazole revealed that it halts cell division, characterised by a significant increase in the length of C. difficile cells and an absence of division septum formation.
This publication is in addition to other recent peer-reviewed literature publications, which in aggregate bolster the preclinical data that highlight ridinilazole’s potential advantages over the current standard of care antibiotics for CDI. Links to the Journal of Antimicrobial Chemotherapy paper, along with the other publications, are available from the programmes section of the Summit website.
About C. difficile Infection
C. difficile infection is a serious healthcare threat in hospitals, long-term care homes and increasingly the wider community with between 450,000 and 700,000 cases of CDI in the US annually. It is caused by an infection of the colon by the bacterium C. difficile, which produces toxins that cause inflammation, severe diarrhoea and in the most serious cases can be fatal. Patients typically develop CDI following the use of broad-spectrum antibiotics that can cause widespread damage to the natural gastrointestinal (gut) flora and allow overgrowth of C. difficile bacteria. Existing CDI treatments are predominantly broad spectrum antibiotics, and these cause further damage to the gut flora and are associated with high rates of recurrent disease. Recurrent disease is the key clinical issue as repeat episodes are typically more severe and associated with an increase in mortality rates and healthcare costs. The economic impact of CDI is significant with one study estimating annual acute care costs at $4.8 billion in the US.
About Ridinilazole
Ridinilazole (SMT19969) is an orally administered small molecule antibiotic that Summit is developing specifically for the treatment of CDI. In preclinical efficacy studies, ridinilazole exhibited a narrow spectrum of activity and had a potent bactericidal effect against all clinical isolates of C. difficile tested. In a Phase 2 proof of concept trial in CDI patients, ridinilazole showed statistical superiority in sustained clinical response (‘SCR’) rates compared to the standard of care, vancomycin. In this trial, SCR was defined as clinical cure at end of treatment and no recurrence of CDI within 30 days of the end of therapy. Ridinilazole has received Qualified Infectious Disease Product (‘QIDP’) designation and has been granted Fast Track status by the US Food and Drug Administration. The QIDP incentives are provided through the US GAIN Act and include an extension of marketing exclusivity for an additional five years upon FDA approval.
About Summit Therapeutics
Summit is a biopharmaceutical company focused on the discovery, development and commercialisation of novel medicines for indications for which there are no existing or only inadequate therapies. Summit is conducting clinical programmes focused on the genetic disease Duchenne muscular dystrophy and the infectious disease C. difficile infection. Further information is available at www.summitplc.com and Summit can be followed on Twitter (@summitplc).
