Clostridium difficile infections (CDIs) are currently recognised as the most prevalent healthcare-acquired infection in the US. Treatment options for CDIs have generally been limited to antibiotics, with orally administered vancomycin representing the standard of care for the disease. However, patients who successfully recover from CDI often suffer from a disrupted gut microbiome that leaves them susceptible to recurrent infections. GlobalData epidemiologists estimate that 23% of patients ages 65 years and older who recover from a CDI in the US will suffer from a recurrence, which increases to 36% for subsequent recurrences.
GlobalData’s primary research has revealed that the need for new treatment options that effectively reduce the rate of recurrence will remain largely intact during the coming years. Furthermore, this unmet need will represent a key opportunity for novel products to enter the market, despite the fact that the FDA approved Merck’s Zinplava (bezlotoxumab) in October 2016 and there are multiple other products by various companies in the pipeline, all of which target CDI recurrence.
Recent drug approvals for CDI have already focused on providing new options for physicians to lower the rate of recurrence. Merck’s Dificid (fidaxomicin), an orally administered antibiotic, was launched in 2011 with the expectation of reducing recurrences of CDI. Unfortunately, the drug has struggled to garner significant patient shares, mostly due to the high treatment cost and limited efficacy against certain C. difficile strains.
For Zinplava, Merck used an alternative approach to address CDI recurrence. Clinical data for this monoclonal antibody indicate a potential reduction of CDI recurrence by approximately one third when administered alongside antibiotic treatment. However, key opinion leaders (KOLs) interviewed by GlobalData were skeptical about Zinplava, citing cost-effectiveness and links to heart failure as potential concerns, effectively limiting the drug’s ability to fully address the unmet need reducing the recurrence rate of CDI.
Current pipeline products seeking to commercialize fecal microbiota transplantation (FMT)—an experimental procedure that is thought to help patients break the cycle of CDI recurrences by transplanting gastrointestinal microorganisms from a healthy donor—include Seres Therapeutics’ SER-109 and Rebiotix’s RBX2660. Both products are currently being positioned to begin pivotal clinical trials in the hope that they can demonstrate strong efficacy in patients suffering from multiple CDI recurrences.
There are also efforts to develop novel antibiotics that may reduce the rate of CDI recurrence. Johnson & Johnson’s cadazolid completed Phase III clinical trials earlier this month, although top-line data have yet to be announced. Summit Therapeutics’ ridinilazole was shown in vitro to be highly selective for C. difficile, which translated into a reduction in CDI recurrence rates during Phase II trials. However, Summit has yet to announce details for a Phase III trial. Both of these pipeline candidates may contribute to fulfilling the unmet need for products that can reduce CDI recurrence, if they reach the market.
Overall, the current pipeline for recurrent CDIs is expected to significantly expand the breadth of treatment options in this space. However, none of the most advanced pipeline products promise to fully address the unmet need of elimination recurrent infections, leaving ample opportunities for future development.