C. difficile Infection
Ridinilazole is our Phase 3 antibiotic to tackle C. difficile infections (CDI)
CDI (C. difficile infection)
CDI is an infection of the colon caused by the bacteria Clostridium difficile. It is characterised by severe diarrhoea but can also result in serious disease complications including bowel perforation, toxic megacolon and sepsis. It can prove fatal in the most severe cases.
Cases per year in the US and Europe.
Annual acute care costs with ~29,000 deaths per year in the US.
Recurrence is the primary clinical issue in CDI as up to 25% of CDI patients have a second episode; the risk of recurrence rises to 65% after a third episode.
CDI is a serious issue in North America and Europe with estimates of more than one million cases of CDI per year in the US and Europe. The US Centers for Disease Control and Prevention (‘CDC’) reports that CDI is responsible for 29,000 deaths per year in the US. The CDC has also designated C. difficile as one of three pathogens that poses an immediate public health threat and requires urgent and aggressive action.
A healthy and diverse microbiome naturally protects against C. difficile colonisation and infection. Patients who contract CDI typically have damaged microbiomes due to prior broad spectrum antibiotic treatments for an unrelated infection. Initial treatment with the current standard of care antibiotic, vancomycin, fails to sustain cures in approximately one third of cases due to further damage that vancomycin causes to patients’ microbiomes. The use of vancomycin leads to a high risk of recurrent disease. The risk of further recurrence rises to 65% after a patient suffers a second episode of CDI. Each recurrent episode of CDI is typically more severe than the prior episode and carries an increased risk of mortality. Reducing recurrent CDI is the key clinical issue.
Ridinilazole is our Phase 3, precision antibiotic in development for front-line CDI treatment to cure the initial infection and reduce disease recurrence. It exemplifies our strategy combining new science and philosophy to create new opportunities.
Ridinilazole is a new mechanism antibiotic. It is highly selective for C. difficile and works to kill the bacteria by stopping cell division.
In a Phase 2 clinical trial called CoDIFy, this selectivity allowed ridinilazole to outperform vancomycin by killing C. difficile while preserving patients’ microbiomes to reduce disease recurrence. Ridinilazole achieved statistical superiority over vancomycin in sustained clinical response (‘SCR’), which captures ridinilazole’s impact on both the initial treatment and disease recurrence.
Ridinilazole has been generally well tolerated in Phase 1 and 2 clinical trials.
With these positive results, ridinilazole has advanced to Phase 3 clinical trials designed to support the right label for treating CDI and reducing recurrences. To do so, the Phase 3 trials will test for superiority over the standard of care, vancomycin, in SCR, which was achieved in CoDIFy. Further, we are gathering health economic outcomes data that we believe will be important to support the commercialisation of ridinilazole, if approved. The Phase 3 clinical trials began in February 2019.
The Phase 3 clinical and regulatory development of ridinilazole is supported in part by a contract worth up to $63.7 million from the US government agency, BARDA. The development of ridinilazole was supported through Phase 2 by the Wellcome Trust.
If the results from our Phase 3 clinical trials of ridinilazole are favourable, we plan to submit applications for US regulatory approval in 2022.
With over one million cases in the US and Europe a year, we believe there is a great opportunity for ridinilazole as a potential front-line agent.
The US Food and Drug Administration (‘FDA’) has designated ridinilazole as a Qualified Infectious Disease Product (‘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. We expect ridinilazole to have exclusivity through 2034 in US, Europe and Japan. Ridinilazole has also been granted Fast Track designation by the FDA.
Latest Research Publications
C. difficile infection / 24 Jun 2019
ASM Hub Track: Pharma Pipeline
Et Al: ASM Microbe 2019
C. difficile infection / 03 Oct 2018
Ridinilazole for Clostridium difficile Infection: Human Gut Microbiome Profiles from a Phase 2 Clinical Trial
R. Vickers Et Al: IDWeek 2018
C. difficile infection / 03 Oct 2018
Selecting Clostridium difficle Infection Outcome Measures Relevant to Public Health Concerns: Experience from Ridinilazole Phase 2 Trial
S. Chowdhury Et Al: IDWeek 2018