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Ridinilazole preserves the gut microbiome of patients with C. difficile infection
03-07-2016
by Lloyd Dunlap  |  Email the author
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OXFORD, U.K.—Summit Therapeutics plc, the drug discovery and development company advancing therapies for Duchenne muscular dystrophy and Clostridium difficile infection (CDI), announces additional positive data from the CoDIFy Phase 2 clinical trial that show the narrow spectrum antibiotic ridinilazole preserves the gut microbiome in CDI patients while the standard of care, vancomycin, inflicts substantial and long-lasting damage on the gut microbiome.
 
“CDI results from damage to the microbiome, and patients experience further collateral damage through the use of broad spectrum antibiotics to treat CDI, leaving them vulnerable to recurrent disease,” commented David R. Snydman, M.D., FACP, FIDSA, chief, Division of Geographic Medicine and Infectious Diseases and Hospital Epidemiologist of Tufts University School of Medicine. “New, selective antibiotics are needed to minimize these high recurrence rates, and ridinilazole demonstrates an exceptional ability to preserve a patient’s microbiome and allow the growth of protective bacteria, which are vital to protecting against CDI.”
 
Preliminary analysis of these new data show ridinilazole 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 stark 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.
 
“These new results from the Phase 2 trial show ridinilazole preserves the patients’ microbiome while simultaneously working to eradicate the C. difficile bacteria. The clinical data strongly suggest that ridinilazole treatment may be better able to protect against recurrent disease than the current standard of care,” commented Glyn Edwards, CEO of Summit Therapeutics. “We believe this approach offers a clear advantage over conventional broad spectrum antibiotics currently used to treat CDI that cause substantial damage to the gut microbiome or approaches that aim to artificially re-establish a damaged gut microbiome following antibiotic treatment.”
 
“As evidenced by our growing body of clinical and preclinical data, we believe ridinilazole has the ideal profile to become a single therapeutic approach capable of both treating the initial infection and reducing the high rates of recurrent disease.”
 
These key microbiome findings strongly support recently reported results from the Phase 2 CoDIFy trial that showed ridinilazole to be statistically superior to vancomycin in sustained clinical response (SCR), a combined endpoint capturing both initial cure and rates of recurrent CDI, with the improved SCR rate following ridinilazole treatment being driven by a large numerical reduction in recurrence. Full microbiome data are expected to be published at a scientific conference in due course.
 
CoDIFy was a double blind, randomized, active controlled, multi-center, 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 SCR with rates of 66.7 percent compared to 42.4 percent for vancomycin.  SCR is defined as cure at the end of therapy and no recurrent disease 30 days post end of therapy. The primary analysis was conducted on the modified intent-to-treat (‘mITT’) population that comprised subjects with CDI confirmed by the presence of free toxin. These additional data on the preserving effect ridinilazole had on the gut microbiome support the top-line Phase 2 data and improvement observed in rates of recurrent disease.
 
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 U.S. annually. It is caused by an infection of the colon by the bacterium C. difficile, which produces toxins that cause inflammation, severe diarrhea 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 U.S.
 
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 U.S. Food and Drug Administration.  The QIDP incentives are provided through the U.S. GAIN Act and include an extension of marketing exclusivity for an additional five years upon FDA approval.
 
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 C. difficile infection.
 
Code: E03091601

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