Number of deaths per14,000
Infection caused by the bacterium C. difficile is a major healthcare threat in hospitals, long-term care homes, and increasingly in the wider community.
We are developing ridinilazole (SMT19969), a highly selective antibiotic that has the potential to treat CDI and reduce disease recurrence, the key clinical issue.
ABOUT C. DIFFICILE INFECTION
CDI is an infection of the colon caused by the bacteria Clostridium difficile that produces toxins that cause inflammation and severe diarrhoea. CDI can also result in serious disease complications including bowel perforation, toxic megacolon and sepsis, and it can prove fatal in the most severe cases. CDI is a serious issue in North America and Europe with estimates of up to 700,000 cases of CDI per year in the US alone. The US Center for Disease Control and Prevention report that CDI is responsible for 14,000 deaths per annum in the US and has designated C. difficile as one of three pathogens that poses an immediate public health threat and requires urgent and aggressive action. In the US, it is estimated that CDI-related acute care costs total $4.8 billion per year.
CDI typically develops following the use of broad spectrum antibiotics that can cause widespread damage to the natural gut flora to allow overgrowth of C. difficile bacteria. The current standard of care CDI treatments are the broad spectrum antibiotics, vancomycin and metronidazole. While effective at reducing levels of C. difficile, these antibiotics also cause significant collateral damage to the gut flora as a result of their broad spectrum activity and leave patients vulnerable to disease recurrence, the primary clinical issue. Each additional episode of the disease is associated with greater disease severity and higher mortality rates. It has been reported that approximately 25% of CDI patients suffer a second episode of the infection, and the risk of further recurrence rises to 65% after a patient suffers a second episode of CDI. Recurrent disease is associated with an increased burden on the healthcare system.
A DIFFERENTIATED ANTIBIOTIC FOR CDI
Ridinilazole (SMT19969) is our first-in-class, novel antibiotic for the treatment of CDI. In preclinical studies and clinical trials conducted to date, ridinilazole has demonstrated potent bactericidal activity for C. difficile with a minimal antibiotic effect against the bacterial groups that comprise the natural gut flora. We believe that this profile means ridinilazole has the potential to selectively target C. difficile without causing collateral damage to the natural gut flora and thereby reduce CDI recurrence rates.
In a Phase 1 clinical trial of ridinilazole in healthy volunteers, ridinilazole was well tolerated at all doses tested. The results from this trial were also consistent with ridinilazole’s highly selective profile, as ridinilazole had a minimal antibiotic effect on the natural gut flora other than total clostridia.
Data from the CoDIFy Phase 2 trial demonstrated statistical superiority of ridinilazole over vancomycin in sustained clinical response (SCR) in the treatment of CDI. SCR was defined as clinical cure at the end of treatment and no recurrence of CDI within 30 days of the end of treatment. The statistical superiority in SCR with ridinilazole was driven by a large numerical reduction in recurrent disease compared with vancomycin. Additionally, ridinilazole was generally well tolerated and the overall adverse event profiles of ridinilazole and vancomycin were comparable. With these promising data, we are now preparing ridinilazole for Phase 3 clinical trials.
The US Food and Drug Administration, or FDA, has designated ridinilazole as a Qualified Infectious Disease Product or QIDP. 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. Ridinilazole has also been granted Fast Track designation by the FDA.
The development of ridinilazole was supported through Phase 2 by the Wellcome Trust following the award to Summit of a prestigious Seeding Drug Discovery and a Translational Research Award.