In mid-June, Seres Therapeutics announced that it had initiated a Phase III trial for SER-109, its flagship product that is being positioned to lower the rate of recurrence for patients suffering from Clostridium difficile infections (CDI). This move positions SER-109 to potentially become the first fecal microbiota transplant (FMT) derived therapy to receive regulatory approval from the US Food and Drug Administration (FDA).
CDIs are a major healthcare burden and C. difficile is now considered one of the most common healthcare-acquired pathogens in the US. Individuals more than 65 years of age are at particular risk of infection, which can result in severe diarrhea and may require surgical intervention.
Current treatment options for a C'difficile infection are mostly dependent on antibiotic treatment and leaves patients susceptible to recurrences. Several pipeline products are being positioned to satisfy this unmet need by providing options to reduce the rate of recurrence in patients with CDIs.
Pipeline product SER-109 was developed by Seres Therapeutics to combe the efficacy associated with FMT for preventing CDI recurrences with a non-invasive route of administration. Available in pill form, SER-109 is based on bacterial spores that are part of a balanced human gut microbiota. These are extracted from donor stool before encapsulated for oral administration.
Due to its unique mode of action, SER-109 generated a lot of excitement during the early stages of clinical development. However, in June 2016 Seres Therapeutics announced that SER-109 had not met the primary endpoint in Phase II trials and that no statistical reduction in the rate of CDI recurrence was observed in patients administered SER-109 compared to a placebo. Further analysis of these results led Seres Therapeutics to believe that the low efficacy was a result PCR diagnostic testing used during trial recruitment, a method that is associated with over-diagnosis of recurrent CDIs.
The recently initiated Phase III trial takes some of the shortcomings of the previous trial into account. For example, patients recruited into the Phase III trial must have been diagnosed with a CDI using a stool toxin immunoassay test rather than a PCR test. The overall dose of SER-109 has also been tripled by extending administration over three days, rather than the one-day regimen used during the Phase II study. Seres Therapeutics will be hoping that their modified trial design will help establish a statistically significant reduction in the rate of CDI to achieve regulatory approval for SER-109.
Aside from developmental hurdles, SER-109 may also face competition from Rebiotix’s RBX2660, another FMT-based product being positioned to reduce the risk of CDI recurrence. RBX2660 recently completed its third Phase II clinical efficacy trial. However, so far no plans for a Phase III trial have been announced by Rebiotix. Both SER-109 and RBX2660 could offer physicians advantageous alternatives to FMT due to full regulatory approval, clear efficacy data, and a defined dosing strategy.