For the first time, the U.S. Food and Drug Administration has approved a stool-based microbial treatment, used to prevent a recurrent diarrheal infection that can become life-threatening.
The approval, announced Wednesday, is years in the making. Researchers have made an effort to harness the protective properties of the complex, diverse but variable microbial communities in the guts and stools of healthy people. At first, rich stools proved to be useful for restoring balance and blocking infection in those whose microbiomes are disrupted – a condition called dysbiosis, which can occur from illness and/or the use of antibiotics. But our understanding of what makes a microbiome healthy, functional and protective remains incomplete.
Doctors, meanwhile, went ahead and informally tried a range of methods to transplant fecal microbiota from healthy donors into patients’ guts — via enemas, tubes through the nose, and capsules full of oral poop. Fecal microbiota transplants (FMTs) have been used to treat a variety of conditions, from obesity to irritable bowel syndrome, to varying degrees of success. But it soon became clear that FMTs were the most effective at preventing recurrent infections 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 gut, producing toxins that can lead to organ failure. Older people, people who are hospitalized and people with weakened immune systems are particularly susceptible to C. diff, which can recur again and again in some vulnerable patients. In the US, C. diff infections are associated with up to 30,000 deaths per year.
With the urgent need for effective treatments against C. diff, regulators were forced to grapple with the dirty issue of regulating and standardizing something as unmanageable and myriad as fecal matter. It also led to years of microbial sleuthing, synthetic slurries, stool donations, and clinical trials.
Now there’s finally a product floating to the top: Rebyota, a mixture of donor stool, saline, and laxative solution that’s given as an enema in a single treatment. It is teeming with heavily screened gut microbes at a concentration of 10,000,000 living organisms per milliliter. Its owner, Switzerland-based Ferring Pharmaceuticals, screens donors and their donated stool for a long list of infectious pathogens and other health factors.
In a Phase III clinical trial of 262 participants – the results of which were published last month – Ferring scientists reported that treatment with Rebyota led to a higher prevention of recurrent C. diff infections than in a placebo group at a rate of 70%, 6 percent in the treatment group compared to 57.5 percent in the placebo group. Prevention of C. diff was defined as absence of C. diff diarrhea for eight weeks after treatment or placebo. The treatment was well tolerated with no serious side effects. The FDA noted that given the variability of the stool, there is a possibility that it may contain an adventitious infectious agent or food allergens.
Rebyota’s approval is “an advancement in the care of patients with recurrent C. difficile infection,” said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, in an announcement. “Recurrent CDI impacts an individual’s quality of life and can also potentially be life-threatening. As the first FDA-approved fecal microbiota product, today’s action represents an important milestone as it provides an additional approved option to prevent recurrent CDI to prevent.”
Ferring, which acquired Rebyota in 2018 when it bought its Minnestoa-based developer Rebiotix, also celebrated the approval.
“We believe this is a major breakthrough in harnessing the power of the human microbiome to address important unmet medical needs. This is the first FDA approval of a live biotherapeutic agent and the culmination of decades of research and clinical development,” said Ferring Chairman Per Falk. “Today’s announcement is not only a milestone for people living with recurrent C. difficile infection, but also represents an important step that promises that many other diseases can be better understood, diagnosed, prevented and treated using our rapidly evolving understanding of the role of the microbiome in human health and disease.”