Fecal Transplants Deserve “Light-Squeeze” Regulatory Approach

To the millions of Americans suffering from difficult-to-treat illnesses such as Parkinson’s disease and multiple sclerosis, relief is painfully elusive. Approved medications only succeed in temporarily managing symptoms. Innovative procedures such as fecal microbiota transplants show early promise in expanding treatment options and safely improving symptoms for a range of chronic diseases. Unfortunately, the Food and Drug Administration (FDA) has poo-pooed this emerging therapy and is determined to impose onerous regulations on fecal transplants. In a recent warning letter to a stool donor bank called Human Microbes, the agency accused the company of pedaling, “both unapproved new drugs and unlicensed biological products.” Treating stool as a drug would spell disaster for donor transplants, skyrocketing costs and flushing innovation down the drain. The FDA can show it gives a crap about patients by embracing a “light-squeeze” regulatory approach and not subjecting fecal microbiota transplants to the same long and expensive process as drug approval.

In a world accustomed to standardized medicines administered by mouth or needle, fecal transplants can be weird and a tough sell. That doesn’t mean the procedure shouldn’t be taken seriously. Slate staff writer Luke Winkie leaves little to the imagination: “Alexandra, a 66-year-old retired woman in D.C., was defrosting a piece of human feces that she purchased over the internet. Her goal was to reduce the stool into a sloshy, biologically rich mixture, which could then be easily transferred past her rectum and into her colon… she laid there allowing her homebrew liquid-fecal elixir to seep into her innards, where she hoped it would bloom new life into her troubled guts.” Donor match sites such as Human Microbes play a middleman role, allowing donors with “healthy, unperturbed, disease-resistant microbiomes” to send their poop to paying participants.

Evidence for this approach is still preliminary, but small studies have found positive results. One 2018 review in Current Infectious Disease Reports found that, for Crohn’s disease, “positive outcomes have been observed in small cohort studies. Most adverse events (AEs) were mild and included transient gastrointestinal symptoms.” A 2023 randomized repeat-dose, placebo-controlled clinical pilot study published in Frontiers in Neurology concluded that Parkinson’s patients receiving transplants, “experienced increased diversity of the intestinal microbiome that was associated with reduction in constipation and improved gut transit and intestinal motility. Fecal microbiota transplantation administration improved subjective motor and non-motor symptoms.”

In 2022, the FDA greenlit a fecal microbiota product called Rebyota designed to prevent recurring Clostridioides difficile (C. difficile) infections. However, the agency has indicated in guidance documents that it will flush away any fecal products from a stool bank or beyond the limited scope of C. difficile treatment. The FDA wants to regulate stool bank “specimens”  as drugs, which usually entails the product sponsor submitting results from two large, “well-designed clinical trials.” This is exceptionally difficult for a product that can differ dramatically based on the quality of the donor’s doo-doo. Because each stool has its own, unique characteristics, each specimen is essentially its own product. Human Microbes’ founder Michael Harrop has stated he wanted to run a clinical trial anyway, but “all I could find were companies charging $1,500 to tell you whether or not it was possible.”

Harrop will try explaining this predicament to the FDA in a meeting and says he is planning on blogging about his experience. But, things don’t seem encouraging because he, “contacted the FDA about getting approved for an IND (investigational new drug) application and never heard back.”

Instead of forcing stool banks to submit to large clinical trials better suited to standardized drug regimens, the FDA should focus on smaller cohort studies in evaluating fecal transplants. Coupled with vigorous safety monitoring, that approach will keep patients safe while allowing them some respite from chronic illness.

Hopefully, the FDA pursues option number two and makes do with the available evidence.