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Summit’s Ridinilazole Preserves Microbiome During Treatment of C. Difficile Infection

  • Microbiome-Sparing Action of Ridinilazole associated with Superiority over Vancomycin in Sustained Clinical Response Rate

OXFORD, United Kingdom, June 20, 2016 (GLOBE NEWSWIRE) -- Summit Therapeutics plc (AIM:SUMM) (NASDAQ:SMMT), the drug discovery and development company advancing therapies for Duchenne muscular dystrophy and Clostridium difficile infection (‘CDI’), announces the presentation of further clinical trial data showing ridinilazole outperformed the standard of care, vancomycin, in the preservation of the gut microbiome of patients during treatment for CDI. These data were derived from the Phase 2 CoDIFy trial and are being presented today during ASM Microbe 2016 in Boston, MA, US.

Ridinilazole is part of a novel structural class of antibiotics with potential for broad use in the treatment of CDI. As previously reported, in a Phase 2 clinical trial called CoDIFy, ridinilazole demonstrated substantial clinical benefit over vancomycin, including a large numerical reduction in recurrent disease. Recurrence of CDI, and consequent failure to achieve a sustained response after treatment, is a major issue in the management of the condition and is promoted by disruption of the gut microbiome, which occurs with current mainstay treatments such as vancomycin.

“Ridinilazole is a shining example of translational medicine, where its high selectivity in the lab has read through to a preserved microbiome in trial patients, ultimately resulting in significantly more sustained clinical responses in a Phase 2 trial compared to the standard of care,” said Dale Gerding, MD, Research Physician, Hines Veterans Affairs Hospital, Professor of Medicine, Loyola University Stritch School of Medicine. “These and additional supporting data presented at ASM Microbe show the broad potential of ridinilazole as a novel treatment for CDI, and I look forward to its continued clinical development.”

In the presentation entitled “Ridinilazole Preserves Major Components of the Intestinal Microbiota During Treatment of Clostridium difficile Infection,” stool samples were obtained from 82 patients enrolled in the CoDIFy Phase 2 trial evaluating the efficacy of ridinilazole compared to vancomycin. These samples were analysed on study entry, days five and ten of treatment, days 25 and 40 post-entry as well as at the time of any recurrence for five specific bacterial groups associated with a healthy gut microbiome (Bacteroides, Prevotella, Enterbactericeae, C. coccoides and C. leptum) and also for total bacteria present. Treatment with vancomycin resulted in a significant decrease (p<0.001) in four of the five bacterial groups (Bacteroides, Prevotella, C. coccoides and C. leptum) at days five and ten, and also resulted in a significant decrease in total bacteria. In contrast, treatment with ridinilazole did not significantly decrease these specific bacterial groups nor the total bacteria. These data suggest ridinilazole may have advantages compared to vancomycin in preserving a healthy gut microbiome during treatment for CDI.

A new analysis from the CoDIFy study evaluating rates of sustained clinical response in prospectively defined subgroups of patients at high risk for recurrence is also being presented at the meeting. Consistent with findings from the entire modified intent-to-treat patient population, where ridinilazole achieved statistical superiority over vancomycin in sustained clinical responses (66.7% vs 42.4%), there were trends favouring ridinilazole in most of these groups, including older patients, those with severe disease and those with previous CDI episodes. Notably, among patients aged 75 and over, 83% (5/6) of patients on ridinilazole had sustained clinical responses compared with 22% (2/9) on vancomycin.

Other posters on ridinilazole presented today report biomarker findings from CoDIFy, data on susceptibility of C. difficile isolates from the trial to antimicrobial agents, and in vitro studies of resistance development.

Copies of all the posters are available from Summit’s website, www.summitplc.com/publications. In addition, a video featuring leading CDI experts, Professor Mark Wilcox of the University of Leeds and Dr Dale Gerding of Hines Veterans Affairs Hospital and Loyola University Stritch School of Medicine, discussing the promise of ridinilazole in the treatment of CDI is available on Summit’s homepage www.summitplc.com.

About CoDIFy
CoDIFy was a double blind, randomized, active controlled, multi-centre, Phase 2 clinical trial that evaluated the efficacy of ridinilazole against vancomycin in a total of 100 patients. Half of the patients received ridinilazole for ten days (200 mg, twice a day), and the remaining half received vancomycin for ten days (125 mg, four times a day). The results of the trial showed ridinilazole achieved statistical superiority in sustained clinical response (SCR) with rates of 66.7% compared to 42.4% for vancomycin. SCR is defined as cure at the end of therapy and no recurrent disease 30 days post end of therapy. In this trial, ridinilazole was found to be highly preserving of the gut microbiome. Ridinilazole treated patients in CoDIFy exhibited no further damage to their microbiome during therapy with a proportion of patients showing initial evidence of recovery of key bacterial groups with roles in protecting from CDI. In contrast, vancomycin treated patients suffered substantial damage to their gut microbiome during treatment and this persisted in many patients during the 30-day post treatment period.

About C. difficile Infection
C. difficile infection is a serious healthcare threat in hospitals, long-term care homes and increasingly the wider community with over one million estimated cases of CDI each year in the United States and Europe. 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 (previously known as 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 designation 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 commercialization of novel medicines for indications for which there are no existing or only inadequate therapies. Summit is conducting clinical programs 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).

For more information, please contact:

Summit Therapeutics
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Forward Looking Statements
Any statements in this press release about Summit’s future expectations, plans and prospects, including but not limited to, statements about the clinical and preclinical development of Summit’s product candidates, the therapeutic potential of Summit’s product candidates, and the timing of initiation, completion and availability of data from clinical trials, and other statements containing the words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "would," and similar expressions, constitute forward looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation of future clinical trials, availability and timing of data from on-going and future clinical trials and the results of such trials, whether preliminary results from a clinical trial will be predictive of the final results of that trial or whether results of early clinical trials or preclinical studies will be indicative of the results of later clinical trials, expectations for regulatory approvals, availability of funding sufficient for Summit’s foreseeable and unforeseeable operating expenses and capital expenditure requirements and other factors discussed in the "Risk Factors" section of filings that Summit makes with the Securities and Exchange Commission including Summit’s Annual Report on Form 20-F for the fiscal year ended January 31, 2016. Accordingly readers should not place undue reliance on forward looking statements or information. In addition, any forward looking statements included in this press release represent Summit’s views only as of the date of this release and should not be relied upon as representing Summit’s views as of any subsequent date. Summit specifically disclaims any obligation to update any forward-looking statements included in this press release.

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Source:Summit Therapeutics PLC