FDA Approves the First Fecal Transplant Therapy

gut bacteria

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Key Takeaways

  • The FDA approved a fecal transplant therapy that can reduce the recurrence of C. diff infection in adults.
  • This is the first approval for fecal transplant therapy in the United States.
  • Other products to treat diseases of the microbiome could follow close behind.

For the first time, federal regulators approved a fecal transplant therapy—a medical procedure that introduces a donor’s stool samples into a patient’s intestine to restore microbial balance.

The drug, called Rebyota, is a one-dose treatment for people who are vulnerable to repeat Clostridioides difficile (C. diff) infections. C. diff commonly causes diarrhea, weight loss, nausea, and abdominal pain, and it can have potentially serious and fatal consequences.

Antibiotics have long been used to treat C. diff infections. But they can also disrupt the beneficial microbes in the gut, which are important to protecting the colon and keeping infections in check.

About one in six patients who get C. diff will be infected with it again within eight weeks, and one in 11 people older than 65 diagnosed with the infection will die within a month, according to the Centers for Disease Control and Prevention. The risk of a recurrent infection increases to 40% after getting C. diff twice and can be up to 65% after the third bout.

Since 2013, the Food and Drug Administration (FDA) has allowed providers to offer fecal microbiota transplants (FMT) as experimental therapies. The Rebyota approval will give patients more direct access to the treatment and open pathways for other FMTs to seek approval.  

“It’s really exciting,” said Sahil Khanna, MBBS, MS, a gastroenterologist and head of the C. diff and gut microbiome research group at Mayo Clinic. “This will help millions of people who get sick from C. difficile infection. And we can also potentially study products like this for other diseases now that we’ve got a pathway for FDA approval.”

Why Antibiotics Aren’t Great for Treating C. diff

The gastrointestinal tract is an ecosystem teeming with microbes. These are important for digesting certain foods, controlling the immune system, and protecting the intestines from disease-causing bacteria. During a C. diff infection, the bacteria release toxins that cause damage to the colon and cause watery diarrhea and abdominal cramping.

While antibiotics can kill off C. diff, other beneficial bacteria can suffer collateral damage, throwing off the balance of the microbiome and leaving the gut susceptible to repeat C. diff infections.

This is partly because antibiotics like vancomycin and Dificid (fidaxomicin) kill part of the C. diff bacteria but don’t always neutralize its spores. FMT, on the other hand, reintroduces microbes that can suppress the proliferation of C. diff and keep it from overtaking the gut.

This is a vicious cycle—the antibiotics that treat the infection could also increase the chances of new infections.

“Unfortunately, C. difficile antibiotics are a victim of their own success. They’re really good at killing C. difficile, but they kill everything else too,” Scott Curry, MD, an assistant professor at the Medical University of South Carolina specializing in FMT and C. diff, told Verywell. “The fecal transplant landscape is meant to fix that problem in one big swoop by giving you back the normal bacteria that are supposed to be in your colon.”

How the Rebyota Fecal Transplant Works

When a patient has a recurrent C. diff infection, their provider will prescribe a course of antibiotics to treat the active infection. Then, after a “washout period,” the patient will visit a clinician’s office to receive Rebyota.

Many fecal transplants are done via a colonoscopy. Rebyota, however, is given through an enema—an injection of fluid through the anus and into the large intestine.

“No bowel preparation is needed as with a colonoscopy. There is no procedure, there’s no sedation, and there is no recovery time that somebody needs from an anesthesia-based procedure,” Khanna said. “That’s the advantage of this over traditional fecal microbiota transplantation in terms of the process.”

The enema is made from the stool of healthy donors that is purified and processed. Ferring Pharmaceuticals, the company that manufactures Rebyota, said it tests the stool for pathogens that could cause infections or adversely alter the microbiome.

Rebyota was tested in five clinical trials with more than 1,000 total participants. This is the largest clinical trial program in the field of microbiome-based therapeutics, according to Ferring.

Patients treated with Rebyota saw a success rate of 70.6%, compared to 57.5% among those who took a placebo. More than 90% of those who had treatment success at eight weeks had a sustained response through six months in both groups.

Curry said clinicians often seek fecal transplantation for patients who are not improving on antibiotics, but C. diff isn’t always the culprit for patients with diarrhea. Even if they test positive for the bacteria, a fecal transplant may not work for them.

Besides, Rebyota can’t be given unless someone has been off their antibiotics for a few days. This could be a problem for some patients who suffer many recurring C. diff infections. If someone is in an ICU with ulcerative colitis, for instance, their provider is unlikely to pause their antibiotic treatment to give them a fecal transplant.

“This is not really a therapy to fix your acute C. diff. This is a therapy to give when your antibiotics for C. diff are nearing their end, and you’re feeling better,” he said. “The problem is now that it’s got an FDA label, people can kind of use it how they best see fit. And I think that’s where it’s going to be very important to educate physicians.”

Accounting for Safety

The fecal matter used to create Rebyota is screened for different kinds of bacteria, infections in the blood, and viral infections like COVID-19, according to Khanna, the lead researcher on the largest Rebyota clinical trial.

“There are a lot of checks and balances that are in place to make sure that there’s minimal to no infection transmission,” Khanna said.

In the clinical trials, more adverse events were reported in the Rebyota group than in those who got a placebo. The most common side effects were stomach pain, diarrhea, bloating, gas, and nausea. There were no reports of infectious transmission from the donor stool.

Despite these positive findings, there is some ambiguity about how the treatment actually works. Curry, who was a principal investigator for a branch of the Rebyota clinical trials, said Ferring considers its product to be proprietary and hasn’t shared with researchers details about how the product is made.

“We don’t fundamentally know what’s in it,” Curry said. “One Rebyota dose could come from one human. It could be pooled from 50 humans or 500 humans. We don’t know—they don’t spell that out in the label.”

Curry said it will be important to collect more safety data on how this product holds up in young people and in those who are immunocompromised, such as cancer patients who are at high risk for recurrent C. diff infections. The treatment doesn’t appear to be safe and effective for people who have a low white blood cell count or are taking any antibiotics.

“We’ve been stuck in this wilderness where patients don’t have access to a therapy that we know works really well. But there’s been a big question mark hanging over [FMT]: Is this safe?” Curry said. “It’s a human product. Human beings can have infectious diseases, and if you’re not careful, you’ll make a bad situation even worse.”

As more microbiota-based therapies come to market, Curry said it will be important to educate providers about how to use them safely.

“This a desperate infection. People are desperately ill, and they need this therapy, so some of these risks are probably worth taking,” Curry said.

There is an ongoing phase 3 clinical trial to study the long-term efficacy and safety of the therapy in an expanded population with fewer enrollment restrictions.

What This Means For You

The FDA approved Rebyota, a fecal transplant therapy that introduces a donor’s stool samples into a patient’s intestine to reduce recurrent C. diff infections. While Rebyota is the first of its kind to be approved in the U.S., clinicians have been giving these treatments experimentally for more than a decade.

4 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  2. Song JH, Kim YS. Recurrent Clostridium difficile infection: risk factors, treatment, and preventionGut Liver. 2019;13(1):16-24. doi:10.5009/gnl18071

  3. Zhu D, Sorg JA, Sun X. Clostridioides difficile biology: sporulation, germination, and corresponding therapies for C. difficile infection. Front Cell Infect Microbiol. 2018;8:29. doi:10.3389/fcimb.2018.00029

  4. Khanna S, Assi M, Lee C, et al. Efficacy and safety of RBX2660 in PUNCH CD3, a phase III, randomized, double-blind, placebo-controlled trial with a Bayesian primary analysis for the prevention of recurrent Clostridioides difficile infectionDrugs. 2022;82(15):1527-1538. doi:10.1007/s40265-022-01797-x

By Claire Bugos
Claire Bugos is a health and science reporter and writer and a 2020 National Association of Science Writers travel fellow.