OXFORD, U.K.—Summit Therapeutics plc, the drug discovery and development company advancing therapies for Duchenne muscular dystrophy and Clostridium difficile infection (CDI), has announced the success of CoDIFy, a Phase 2 proof of concept clinical trial that evaluated the novel, oral antibiotic, ridinilazole (SMT19969) against the current standard of care, vancomycin, for the treatment of CDI.
The Phase 2 trial exceeded its primary endpoint with ridinilazole achieving statistical superiority over vancomycin in sustained clinical response (SCR) using the pre-specified 90 percent confidence interval, with SCR rates of 66.7 percent for ridinilazole compared to 42.4 percent for vancomycin. SCR was defined as clinical cure at end of treatment and no recurrence of CDI within 30 days of the end of treatment. The statistical superiority in SCR with ridinilazole in this trial was driven by a large numerical reduction in recurrent disease compared with vancomycin.
"These outstanding clinical data from CoDIFy strongly support the profile of ridinilazole as a narrow spectrum antibiotic with the potential to both treat the initial infection and substantially reduce recurrent disease," commented Glyn Edwards, CEO of Summit. "There is a vital need for potent new antibiotics, and the potential of ridinilazole has attracted great interest. Based on the positive top-line results from the CoDIFy trial, we will now evaluate the optimal path to advance ridinilazole into Phase 3 clinical trials. In addition, Summit sincerely thanks the Wellcome Trust for their support in the development of ridinilazole that has helped to achieve this clinical proof of concept milestone."
"The healthcare community is acutely aware of the major threat CDI poses, particularly given widespread antibiotic use and our aging population," said Professor Mark Wilcox, consultant icrobiologist and head of microbiology 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. "These clinical data suggest that ridinilazole could become an important new treatment option for CDI with the potential to reduce the high rates of recurrent disease that remain a key clinical challenge. I, and many other healthcare practitioners, look forward to the continued clinical development of this compound."
CoDIFy was a double blind, randomized, active controlled, multicenter, 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 trial was conducted in the United States and Canada. The primary endpoint was non-inferiority of ridinilazole compared to vancomycin in SCR. The trial met its primary endpoint with ridinilazole achieving an SCR rate of 66.7 percemt compared to 42.4 percent for vancomycin (non-inferiority margin of 15 percent, p=0.0004). This also represents statistical superiority of ridinilazole over vancomycin using the pre-specified 90 percent confidence interval. 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. Ridinilazole was generally well tolerated and the overall adverse event profiles of ridinilazole and vancomycin were comparable. More detailed findings from the trial will be reported at relevant conferences and in peer-reviewed journals.
The development of ridinilazole was financially supported through to completion of this Phase 2 clinical trial by Seeding Drug Discovery and Translational Awards from the Wellcome Trust. Ridinilazole has received Qualified Infectious Disease Product, or QIDP, designation and has been granted Fast Track status from the U.S. Food and Drug Administration.
C. difficile infection is a serious healthcare threat in hospitals, long-term care facilities 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 bacteria 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 U.S.
Ridinilazole 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.
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.