Clostridium difficile, the most common healthcare-acquired superbug, is estimated to have been responsible for over 29,000 deaths in the US during 2011. Antibiotics are currently used as a first-line treatment for C. difficile infections (CDIs); however, they can leave a patient susceptible to further infection.

Rebiotix hopes to solve this problem with its pipeline product, RBX2660. The company recently announced top-line results from an open-label, Phase II trial known as PUNCH Open Label, which investigated whether the administration of RBX2660 could reduce the rate of CDI recurrence. After an eight-week observational period following treatment, 78.8% of patients who had received RBX2660 suffered no further recurrence, compared to 51.8% in a historical control.  

RBX2660 has been developed as an enema-delivered form of fecal microbiota transplant (FMT)—an experimental procedure that some experts see as the future of CDI treatment. During FMT, healthy individuals donate stool, which is transplanted directly into the gut of a patient suffering from recurrent CDI. In doing so, the patients gut is infused with microorganisms from the donor, which may compete with C. difficile and in turn provide colonization resistance against future infections.  

Difficulty of replicating results for FMT therapies

Although there are many published case studies that suggest FMT might be an effective treatment for recurrent CDIs, it has proven difficult to replicate these results in randomized clinical trials, which experts interviewed by GlobalData attributed to the lack of a standardized procedure. Some companies, including Rebiotix, have seen this niche as an opportunity to develop a standardized manufacturing process for a stool-derived infusion, thereby generating the reliable clinical data required to bring the product to market.

However, demonstrating the clinical efficacy of RBX2660 has been a challenging task. In the first open-label, Phase II trial, the efficacy of RBX2660 was found to be lower than expected at 51.6% after a single administration. The second trial, a double-blinded, placebo-controlled study, indicated improved efficacy after one infusion compared to the placebo control (66.7% versus 45.5%) although the study had limited statistical validity (P = 0.048). Nevertheless, after completing three Phase II studies, Rebiotix is optimistic that the recently announced results will justify initiation of a Phase III trial for RBX2660.

Rebiotix may find itself facing competition from another FMT-derived product, Seres Therapeutics’ SER-109. SER-109 suffered a setback last summer, when it failed to reach the primary endpoint in a Phase IIb clinical trial. However, Seres Therapeutics recently announced plans to initiate a pivotal Phase II trial that it hopes will address the problems encountered in its earlier study.  If SER-109 achieves regulatory approval, its orally-administered capsules could prove more attractive to physicians than other available routes of administration for FMTs.