For the first time, the US Food and Drug Administration has approved a stool-based microbial treatment used to prevent life-threatening recurrent diarrheal infections.
The approval announced Wednesday has been years in the making. Researchers are trying to harness the protective qualities of the complex, diverse, but variable microbial communities found in the guts and feces of healthy people. Previously, rich stool microbiomes have proven beneficial in restoring balance and preventing infection in people—a condition called dysbiosis, which can result from disease and/or antibiotic drug use. But our understanding of what makes the microbiome healthy, functional, and protective remains incomplete.
Meanwhile, doctors have gone ahead, informally trying a number of methods to transfer fecal microbiota from healthy donors into the guts of patients—via enemas, nasal tubes, and oral capsules filled with feces. Fecal microbiota transplantation (FMT) has been used to treat diseases ranging from obesity to irritable bowel syndrome with mixed success. However, it quickly became clear that FMTs were most effective in preventing recurrent infection Clostridioides difficile (C. difficile or simply C. diff).
C. diff bacteria cause diarrhea and significant inflammation in the colon. Severe infections can be life-threatening. In people with dysbiosis, C. diff can multiply in the intestines and produce toxins that can cause organ failure. The elderly, the hospitalized, and people with weakened immune systems are particularly susceptible to C. diff, which can recur repeatedly in some susceptible patients. In the United States, C. diff infections are associated with up to 30,000 deaths per year.
With the demand for effective treatments against C. diff, regulators have been forced to tackle the difficult task of regulating and standardizing something as unruly and myriad as feces. It also led to years of microbial sleuthing, synthetic cuttings, stool donations, and clinical trials.
A solid success
Now, one product has finally come to the fore: Rebiota, a mixture of donor stool, saline, and a laxative solution, given as an enema in one treatment. It is full of tightly screened gut microbes at a concentration of 10,000,000 viable organisms per milliliter. Its owner, Switzerland-based Ferring Pharmaceuticals, screens donors and their donated feces for a long list of infectious pathogens and other health factors.
In a Phase III clinical trial with 262 participants whose results were published last month, Ferring scientists reported that treatment with Rebiota resulted in a 70.6 percent higher prevention of recurrent C. diff infections than the placebo group. treatment group compared to 57.5 percent in the placebo group. Prevention of C. diff was defined as the absence of C. diff diarrhea for eight weeks after treatment or placebo. The treatment was well tolerated, there were no serious side effects. The FDA noted that given the variability of stool, there is the potential for it to contain an unexpected infectious agent or food allergens.
Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said in a statement that Rebiota’s approval “is a breakthrough in the care of patients with recurrent C. difficile infection.” “Recurrent CDI affects an individual’s quality of life and can also be potentially life-threatening. As the first fecal microbiota product approved by the FDA, today’s action represents an important milestone as it provides an additional approved option to prevent recurrent CDI.” does.”
Ferring, which acquired Rebiota’s Minnesota-based developer Rebiotix in 2018, also noted the approval.
“We believe this is a major advance in harnessing the power of the human microbiome to address significant unmet medical needs. This is the first FDA approval of a live biotherapeutic and is the culmination of decades of research and clinical development,” said Per Falk, president of Ferring. “Today’s announcement is not only a milestone for people living with recurrent C. difficile infection, but also a sign. This is an important step that promises to better understand, diagnose, prevent and treat many other diseases by leveraging our rapidly evolving understanding of the microbiome’s role in human health and disease.”