Prescription poo has arrived: FDA approves fecal sludge for unwavering diarrhea

For the first time, the United States Food and Drug Administration has granted approval for a fecal-based microbial treatment, which is used to prevent recurrent diarrheal infection that can become fatal.

Approval, announced Wednesday, takes years. Researchers have worked to harness the protective qualities of the complex, diverse but variable microbial communities found in the gut and feces of healthy people. Early on, rich feces proved helpful in restoring balance and blocking infection in those whose microbiomes have been disrupted – a condition called dysbiosis, which can occur as a result of illness and/or use of antibiotics. But our understanding of what makes a healthy, functional and protective microbiome remains incomplete.

Doctors, meanwhile, have pushed ahead, informally trying an array of methods to transplant faecal microbiota from healthy donors into patients’ intestines – via enemas, nose tubes and oral capsules filled with of poop. Fecal microbiota transplants (FMT) have been used to treat a variety of conditions, from obesity to irritable bowel syndrome, with mixed success. But it quickly became clear that FMT was the most effective in preventing recurrent infections from Clostridioides difficile (C.diff or simply C.diff).

C. diff bacteria cause diarrhea and significant inflammation of the colon. Serious infections can be life threatening. In people with dysbiosis, C. diff can overgrow in the intestines, producing toxins that can lead to organ failure. The elderly, those in hospital, and people with weakened immune systems are particularly susceptible to C. diff, which can recur repeatedly in some vulnerable patients. In the United States, C. diff infections are associated with up to 30,000 deaths per year.

With the pressing need for effective treatments for C. diff, regulators have been forced to grapple with the delicate issue of regulating and standardizing something as unruly and myriad as feces. It has also led to years of microbial research, synthetic sludge, stool donations and clinical trials.

Solid success

Today, one product has finally risen to the top: Rebyota, a mixture of donor stool, saline solution and laxative solution given in a single treatment as an enema. It is teeming with tightly controlled 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 involving 262 participants, the results of which were published last month, Ferring scientists reported that treatment with Rebyota led to a higher rate of prevention of recurrent C. diff infections than in a group placebo at a rate of 70.6 percent in the treatment group versus 57.5 percent in the placebo group. Prevention of C. diff was defined as freedom from 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 feces, it is possible that they contain an unexpected infectious agent or food allergens.

Rebyota’s approval is “a step forward in the management of patients who have recurrent C. difficile infection,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said in a statement. “Recurrent CDI impacts an individual’s quality of life and can also be potentially life threatening. As the first faecal microbiota product approved by the FDA, today’s action represents an important milestone, as it provides an additional approved option to prevent recurrent CDI.

Ferring, which acquired Rebyota in 2018 when buying its Minnesota-based developer Rebiotix, also celebrated the approval.

“We believe this is a major breakthrough in harnessing the power of the human microbiome to address significant unmet medical needs. This is the first FDA approval of a living biotherapeutic and the culmination of decades of clinical research and development,” said Ferring Chairman Per Falk. “Today’s announcement is not only a significant milestone for people living with recurrent C. difficile infection, but also represents a milestone that promises that many other diseases could be better understood, diagnosed, prevented and treated using our rapidly evolving knowledge of the role of the microbiome in human health and disease.