In a presentation at the 6th International C diff Awareness Conference and Health EXPO, November 8, 2018, in Philadelphia, Pennsylvania, Sahil Khanna, MBBS, MS, an associate professor of medicine in the department of gastroenterology at the Mayo Clinic, highlighted the available information about the efficacy of fecal transplants for Clostridium difficile.
In particular, Khanna, discussed the challenges for managing recurrent C diff infections. Initial infection with C diff results in a 20% chance of recurrence, but after 2 infections, the risk of recurrence rises to about 40%, and after 3 or more infections, the risk of recurrence is as high as 60%. Because common antibiotic treatments for the infection cause disruption of the gut microbiome, the risk of recurrence grows.
In his presentation, Khanna focused on the literature behind fecal transplant for C diff and clinical trials for new investigational candidates.
“What we've learned over the years is that FMT, or fecal transplantation, is efficacious more than 85% to 90% of times in patients who have this deadly recurrent infection,” Khana told Contagion® in an interview. “We've also learned that it does not matter what donor it comes from as long donors are screened rigorously. [Furthermore,] fresh stool or frozen stool are similarly efficacious to prevent future recurrent C diff infection.”
According to Khana, recent clinical trials and clinical observations have indicated that the fecal transplant process is heterogeneous. Therefore, future research should focus on streamlining and standardizing the process.
Some of the key clinical trials being conducted include a phase 3 trial for a candidate called RBX2660. A single dose of the candidate was found to be superior to placebo in a double-blind phase 2 trial. Another candidate, SER-109, demonstrated promise in phase 1 trials, and a subset of patients in phase 2 trials, and is now being evaluated in phase 3 trials.
In his research, Khanna has focused on a newer product, RBX7455, a lyophilized capsule that is stable at room temperature, which allows patients to store multiple doses of the product at home, without refrigeration.
In an open-label, nonblinded, phase 1 study, that focused on dosing, the investigators enrolled 30 participants who had 2 or more episodes of C diff infection and had completed antibiotic therapy. The participants were sorted into 1 of 3 cohorts. The first cohort received 4 capsules twice a day for 4 days, the second cohort received 4 capsules twice a day for 2 days, and a third cohort received 2 capsules twice a day for 2 days.
At the conclusion of the study, the third cohort had a success rate of 100%. The combined success rate of the 3 cohorts was 90% and future recurrence of C diff was not observed in any of the participants. The investigators also observed that important bacteria in the gut microflora increased, while harmful bacteria decreased. When analyzing adverse events, the investigators did not find any directly attributable to the product.
According to Khanna, the next steps for RBX7455 involve a placebo-controlled trial, evaluating 1 of the 3 doses evaluated in the previous trial.
“Overall, the field is moving towards standardized therapies. I think in the next few years we will have 1 or more of these standardized therapies approved by the US Food and Drug Administration and they will probably replace conventional donor directed microbiome therapies,” Khanna concluded.
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