Microbiota restoration therapy has become a standard treatment for recurrent Clostridioides difficile infection (rCDI). In this article, we review the studies supporting the licensure of two live biotherapeutic products (LBPs) designed to prevent rCDI and to provide clinicians with a perspective on their differences. PubMed was reviewed on 1 October 2023, for all papers published concerning the current Food and Drug Administration allowance of the use of fecal microbiota transplantation (FMT) and the studies that led to the licensure of RBX2660 (REBYOTA™), generic name, fecal microbiota, live-jslm, and SER-109 (VOWST™), generic name, fecal microbiota spores, live-brpk. OpenBiome continues to produce fecal products for patients with rCDI at their treatment sites, and the American Gastroenterology Association has a National Registry focused on long-term safety of administering fecal microbiota products. The science behind the licensing of fecal microbiota, live-jslm, a consortium of fecal anaerobes found in stool augmented with strains of Bacteroidetes and fecal microbiota spores, live-brpk, a mixture of 50 species of purified Firmicutes spores is reviewed. Both products appear to be safe in clinical trials and effective in reducing rCDI episodes by mechanisms established for FMT, including normalization of α- and β-diversity of the microbiome and by increasing fecal secondary bile acids. The different makeup of the two LBPs suggests that rCDI responds to a variety of engrafting microbiota which explains why nearly all donors in FMT of rCDI are generally effective. Fecal microbiota, live-jslm has also been shown to successfully treat rCDI in elderly patients with advanced comorbidities. With the licensure of two novel LBPs, we are entering a new phase of microbiota replacement therapy. Having standardized manufacturing and proper monitoring of products, harnessing the microbiome to control and prevent disease has a new beginning.
Keywords: Clostridioides difficile; REBYOTA™; VOWST; fecal microbiota transplantation; live biotherapeutic products.
Licensure of two new live biotherapeutic products to treat recurrent C difficile infection is changing the landscape for treatment of this common and often serious infection Microbiota replacement therapy is the most effective way to prevent multiple recurrences of C difficile infection. The article discusses where fecal microbiota transplantation is available in North America. The major focus is on two recently licensed live biotherapeutic products, RBX2660 (REBYOTA), generic name fecal microbiota, live-jslm and SER-109 (VOWST), generic fecal microbiota spores, live-brpk, manufactured under standardized methods which should be safer and more standardized in response. The article compares the new LBPs for safety, effectiveness, cost to help clinicians make decisions. The licensure and availability of two safe and effective standardized and regulated biotherapies, fecal microbiota, live-jslm and fecal microbiota spores, live-brpk, for preventing rCDI is a critical advance in medical management. Both treatments were shown to cure rCDI, to normalize the microbiome of the treated patients by reducing proportions of proinflammatory Enterobacteriaceae and increasing the α- and β-diversity of the microbiome, and to convert primary bile acids to C. difficile-inhibiting secondary bile acids in fecal samples. Both products included follow-up studies show durable cure without important short-term adverse events. The two recently licensed LBP differ in a number of ways. Fecal microbiota, live-jslm is a broad consortium of microbiota expected in a healthy donor fecal samples, including all the major phyla including Firmicutes. It is augmented with strains of Bacteroidetes, while fecal microbiota spores, live-brpk is ethanol washed spores exclusively within the phylum of Firmicutes. The fact that both products are effective in preventing rCDI support the idea that bacterial restoration in rCDI can be achieved by transplantation of a variety of different microbiota. This is seen in FMT for rCDI where it is generally accepted that all healthy adults are suitable donors and large number of donors can be included unscreened for microbiome diversity in a stool bank such as OpenBiome. When treating conditions other than CDI, the specific makeup of an LBP may need to be adjusted. One way around the unique microbiome requirements of non-CDI illnesses with dysbiosis is to administer FMT product derived from multiple donors. Evidence developed and presented here indicate that the two new LBPs are effective in treating rCDI, although head-to-head comparisons have not been carried out. fecal microbiota, live-jslm is a more traditional microbiome restoration product employing a full range of microbiota. fecal microbiota spores, live-brpk is novel in design and is based on the selection of Firmicutes spores with a narrower range of bioactivity. The future of microbiota-therapy has gotten brighter with the licensure of fecal microbiota, live-jslm and fecal microbiota spores, live-brpk.
© The Author(s), 2024.