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78 GASTROENTEROLOGY A new hope for recurrent C. diff patients: 2 GIs discuss the study behind potential new therapy By Riz Hatton T wo gastroenterologists spoke with Becker's to discuss research challenges, advice for early-career physicians and more. e physicians participated in a study published in e New England Journal of Medicine, showing the potential oral microbiome therapy SER-109 could have to fight recurrent Clostridioides difficile. Paul Feuerstadt, MD, is a practicing gastroenterologist at the PACT- Gastroenterology Center in Hamden, Conn. Louis Korman, MD, is co-director of Chevy Chase Clinical Research at Capital Digestive Care in Silver Spring, Md. Question: How is research conducted in your independent GI practices, and how does it dif- fer from the academic setting? Dr. Paul Feuerstadt: Research in our practice is similar to the academic setting in how studies are conducted and structured, since everyone involved in the study follows the same protocol. What pri- vate practices offer are a group of patients that are sometimes more reflective of real-world practice. Within private practice settings, the opportunity to participate in clinical trials usually involves somewhat less bureaucracy and a more focused approach. We only participate in a handful of selected trials that fit with the expertise of the provid- ers in our practice. Dr. Louis Korman: ere have been some of us at Capital Digestive Care and its prior incarnations who have been doing research for the past 30 years in some capacity. We've probably done hundreds of studies on different diseases like inflammatory bowel disease, chronic constipation, gastroparesis and many others. It differs from academic research in that academic settings have a general infrastructure that supports research throughout the organization. e benefit of being in a community setting is that you have a wide range of patients that you are seeing every day, but it's also challenging because you may not have the support that the research infrastructure provides. Q: What gave you the idea to consider SER- 109 as a treatment option and what inspired you to conduct this study? PF: SER-109 is an exciting product that is a targeted narrow- spectrum therapeutic for the microbiota. It specifically addresses one of the deficiencies in the microbiota that we see in patients who get multiple recurrences of C. difficile infection. Given this logical treatment, it was exciting to have the opportunity to participate in this clinical trial and offer this to our patients. is study, along with the phase 3 study for RBX-2660 and the phase 2 studies for CP101 and VE303, all of which are microbiota-based live biotherapeutics focused on the reduction of recurrence of C. difficile infection when used in addition to a standard of care antimicrobial, fit nicely into our patient population since our offices are a tertiary/quaternary care center for patients with multiple recurrences of C. difficile infection. Many of these patients with chronic disease are looking for alterna- tive options to what is currently available since they have usually failed those therapies. Given this, offering these clinical trials offers hope and a new treatment for these patients. LK: We've been doing C. difficile studies for many years, and we've all been looking for an alternative to fecal transplants. We were involved in some initial trials, including looking at using this therapy for ulcerative colitis. It was important to support this study because the alternative way of treating people with recurring C. difficile, basically with fecal transplant, was very difficult and annoying. And those studies weren't even really funded because who is going to pay for a fecal transplant study? Our group was involved in other studies with Seres erapeutics, and the opportunity to work with Dr. Feuerstadt and the other investigators was compelling. Q: What was the most challenging part about working on this study? PF: Clinical trials require a lot of attention to detail and this study was no different. e SER-109 study required that the diagnostic test for C. difficile be very specific to the study protocol. is led to very accurate diagnosis within the study, but patients did not always pres- ent from referring providers having had the specific tests that were required by the study. Many patients needed to be re-tested or were ineligible to participate in the trial because the test that was used to diagnose the patient was not the one required for study entry and the patient was already on an antimicrobial, rendering the patient ineli- gible for re-testing since the antimicrobial will frequently result in a false-positive test. erefore, many patients who would have been good candidates could not participate due to the study design. With that consideration in mind, the study was very clean and identified a group of patients who truly had C. difficile infection. LK: ere are challenges with every study, but given the way that we previously treated C. diff with fecal transplants, those studies were much more difficult and there wasn't any funding to conduct them. Of course, finding participants is always a challenge. But other than that, the only other tricky thing was getting the timing right in terms of documenting C. difficile, making sure the patient was treated for a certain amount of time and that they received the active SER-109 drug within a certain number of days aer they finished treatment. Q: How do you think the findings from this study will affect the way the industry treats Clostridioides difficile? PF: e SER-109 study was the first phase 3 clinical trial to publish their results in manuscript form considering a microbiota-based live biotherapeutic treatment. is is exciting because we believe the future of therapeutics for many diseases might involve this type of manipulation of the microbiota. In the case of C. difficile, we clearly understand the deficiency that SER-109 replaces. e therapy showed excellent results in clinical practice through the significant differ- ence in rates of recurrence seen in the population with recurrent C. difficile infection, but also with the basic science considerations with the alterations of the microbiota presented within the study. It is awe-