Easy Access to Conventional FMT Continues — for Now

Although the US Food and Drug Administration (FDA) has approved two microbial therapies to prevent recurrent Clostridioides difficile infection (CDI), the preferred treatment of conventional fecal microbiota transplantation (FMT) for severely affected patients may no longer be readily available.

An FDA guidance issued in November 2022 limiting stool banks from providing donor material for FMT, unless they meet stringent requirements, was scheduled to be fully enforced at the end of October. However, objections from American Gastroenterological Association (AGA) and other stakeholders led to a reprieve to the end of this year.

CDI is the leading cause of antibiotic- and healthcare-associated infective diarrhea in the United States, affecting approximately 500,000 people annually, of whom an estimated 30,000 would die, according to recent data. The FDA approved Rebyota (fecal microbiota, live-jslm) and Vowst (fecal microbiota spores, live-brpk) in December 2022 and April 2023, respectively, for adults who have completed antibiotic treatment.

Conventional FMT using stool from known donors or a stool bank is a safe and effective option for patients with recurrent, refractory, and severe/fulminant CDI, as well as for pediatric patients, for whom the new drugs are not approved, Colleen R. Kelly, MD, of Brigham and Women’s Hospital, Boston, told Medscape Medical News.

“The currently approved FMT therapeutics largely excluded immunocompromised patients from their clinical trials, so it is unknown how effective or safe these will be in this population,” added Kelly, who is co-principal investigator for AGA’s FMT National Registry.

Notably, AGA published guidelines on FMT earlier this year that recommended “conventional FMT” rather than either Rebyota or Vowst for patients with recurrent, refractory, or severe CDI.

“We are seeing patients who fail to achieve cure after treatment with one or both approved products,” Kelly said. “These formulations are also much more expensive [than FMT] and, depending on the type of insurance a patient has, may cost thousands of dollars per dose/treatment course.” 

Conventional FMT Access in Jeopardy

Stool banks have supplied donor material for FMT for more than a decade, according to the guideline from AGA. However, the FDA now said that stool banks have to maintain an Investigational New Drug [IND] to continue to supply FMT material for clinical use.

The major provider of conventional FMT in the United States is the nonprofit stool bank, OpenBiome.

Following the issuance of the FDA’s guidance in November 2022, OpenBiome tried to find a path forward that would enable the organization to continue providing FMT despite the update, including through the FDA’s “real-world evidence,” program, but it was not successful, Kelly explained.

Knowing that FDA was moving toward enforcing the November 2022 guidance, the organization began to notify the providers who rely on their donor material for FMT that it would not be available after October 31, 2024.

This triggered a response from physicians and patient advocacy groups, including a letter on October 8, 2024, expressing concerns about loss of access to FMT sent to Peter Marks, MD, PhD, head of the Center for Biologics Evaluation and Research, from AGA and its collaborating national organizations: The Infectious Diseases Society of America; the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition; the Crohn’s & Colitis Foundation; and the Peggy Lillis Foundation.

The result was a temporary extension during which OpenBiome could continue to provide FMT through December 31, 2024, provided it submitted an IND phase 2 protocol application to the FDA by November 30, 2024.

OpenBiome submitted the IND application on November 29, 2024, at which point the FDA had 30 days to respond, OpenBiome Executive Director Julie O’Brien told Medscape Medical News.

“We can and will continue to provide investigational FMT…through the end of December, or as soon as our inventory is exhausted,” O’Brien said.

“ We are hopeful that many centers will have continued access and be able to treat their patients under this IND protocol,” Kelly said. “However, unless FDA continues allowing OpenBiome to supply all sites with banked donor material, many [vulnerable] patients will lose access to FMT, and, in cases of those with severe/fulminant infections, some may die.”

Other FMT Options

For now, physicians who have become accustomed to the supply of “readily available, safe, effective, and affordable donor material from OpenBiome” should be aware that the November 2022 guidance provides a “loophole” that could help ensure access, regardless of what happens after the extension, Kelly said.

The guidance pertains to stool banks but clarifies that an “establishment that collects or prepares FMT products solely under the direction of licensed healthcare providers for the purpose of treating their patients (eg, a hospital laboratory) is not considered to be a stool bank under this guidance.”

“This means that physicians could identify and screen individual donors and use their stool to treat patients without an IND from the FDA,” Kelly said. “This is actually what many of us did prior to the emergence of OpenBiome.” 

In cases of severe/fulminant infection, when patients are at risk for death, a directed donor, such as a family member, could be screened. After some basic serologic and stool studies, the donor’s fecal material could be mixed with saline and administered.

“With an appropriate informed consent and the current guidelines supporting conventional FMT for this indication, it would not put a physician at high medicolegal risk,” she said.

Larger hospital systems could develop a system to identify and screen donors and keep safe material on hand for patients with recurrent or severe CDI, Kelly suggested. Such a hospital supply would also not technically be considered a stool bank by the FDA.

In addition, if a patient with recurrent CDI tries and fails the approved products, the physician can seek an emergency use IND for that patient and may get permission to use material from OpenBiome or another stool bank, she said.

“Unfortunately, none of these options will be as easy as what we have been doing for the past decade, and we will need to continue to jump through some hoops to get these patients the treatment they need,” Kelly said.

Meanwhile, “AGA is continuing to support the FMT National Patient Registry, which is collecting important real-world data on FMT efficacy and safety and is intensifying efforts to enroll patients treated with severe/fulminant infections,” she said.

The FDA provided Medscape Medical News with background on its policies but said it can’t comment on the situation with OpenBiome.

OpenBiome said it will provide updates on its website.

Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.