The microbiota-based live therapeutic had a 68.3% success rate when administered following antibiotic treatment, versus a 55% success rate in a placebo group.
New clinical trial data suggests an investigational microbiota-based live biotherapeutic leads to a significant reduction in the risk of Clostridioides difficile infection (CDI) recurrence when administered to patients following standard-of-care antibiotics.
The data, presented at the American Gastroenterology Association’s Digestive Disease Week conference in San Diego, affirm the benefits of using microbiota-based therapeutics to alter patients’ gut microbiota to reduce susceptibility to repeated infection.
Lead author Paul Feuerstadt, MD, of the PACT Gastroenterology Center, told Contagion that the biotherapeutic is based on the concept of fecal microbiota transplantation (FMT), a long-established concept in which a stool sample from a healthy donor is transplanted into a patient in hopes of repopulating the recipient’s microbiome with a healthy mix of microorganisms.
While the data behind FMT are encouraging, Feuerstadt said the procedure is still surrounded by significant questions.
“The problem is that there's heterogeneity of those trials, there's heterogeneity of the efficacy analysis, heterogeneity of the safety analysis, but most importantly, there's heterogeneity of the products themselves,” he said.
The heterogeneity within the products means clinicians cannot fully predict the results of a particular FMT procedure, since one healthy sample might vary from the next in important, but hard to define, ways.
That uncertainty has created an opportunity for pharmaceutical products. In this case, Feuerstadt and colleagues investigated Ferring Pharmaceuticals’ RBX2660, a broad-spectrum biotherapeutic product manufactured from live, human-derived microbes that uses standardized screening and controls to ensure the product is safe and its results replicable. The therapy has been granted Fast Track, Orphan, and Breakthrough Therapy designations by the Food and Drug Administration.
“What makes RBX2660 different from a fecal transplant is the broad donor screening—the pathogen screening—which goes well beyond any individual practitioner or really healthcare system’s quality metrics,” he said. “There's also quality metrics on the product, and then a proprietary process creating that broad consortium of spore and non-spore forming bacteria, including bacteroides.”
The newly released data concerns RBX2660’s ability to reduce CDI recurrence versus placebo. The data include subgroup analyses using integrated efficacy results from the PUNCH CD2 phase 2b trial and the PUNCH CD3 phase 3 trial. In the studies, adults with documented recurrent CDI were treated with standard-of-care antibiotics and then randomly assigned to receive either RBX2660 (221 patients) or placebo (131 patients).
After 8 weeks, the data showed RBX2660 had a treatment success rate of 68.3%, compared to 55.0% in the placebo group. Furthermore, the results indicated that the treatment had a similarly high success rate across subgroups based on age, sex, race, number previous CDI episodes, and other factors.
“So really, what we're seeing here is an important signal, which states that across the board regardless of subgroup, its product shows consistent safety and efficacy,” Feuerstadt said. “Previously, we knew that it worked in a broad population, but this really nails it down that you don't need to subgroup the patients and target therapy. This can be used broadly for our patients with recurrent C difficile.”
Feuerstadt said the data are exciting given the striking effect of CDI on the healthcare system. He noted that about 500,000 people test positive for CDI in the United States each year, and roughly one-quarter of those patients will experience recurrence. Those who experience recurrence face a much higher risk of multiple recurrences, he noted.
Feuerstadt said he hopes these data help lead to FDA approval for RBX2660, potentially in the next 12-16 months, but he said insights from the study and others like it could also be used to expand the use of this type of product to other disease states.
“The future is so bright here,” he said, “and we can see the light at the end of the tunnel.”