An icky ticket to better health

The U.S. Food and Drug Administration approved the first oral pill derived from human feces on April 26. Despite the “ick factor,” that’s good news for about a half million Americans suffering from Clostridioides difficile, or C. diff, bacterial infections yearly.

Seres Therapeutics produces the therapy, which it markets under the brand name Vowst. Its intended use is as a prevention measure against recurrent C. diff infections in individuals age 18 and older. Recurrent C. diff can cause potentially fatal diarrhea and inflammation of the colon, particularly in immunocompromised and older adults. While some medical experts say the new pill offers an attractive alternative to the current status quo, a fecal microbiota transplant, others are more skeptical of its efficacy.

Microbiota refers to all the microorganisms, including bacteria, viruses, fungi, and protozoa, living in the human body. During a fecal microbiota transplant (FMT), a patient typically undergoes a colonoscopy to transplant healthy bacteria from the feces of a donor. The beneficial bacteria, destroyed by antibiotics used to treat C. diff initially, can then mount an immune response.

With Vowst, instead of undergoing FMT, recurrent C. diff. patients can follow a regimen of four daily capsules taken for three consecutive days. “The approval of Vowst is an incredible moment for Seres, and we think it’s just the beginning of what is possible with microbiome therapeutics,” CEO Eric Shaff said in a conference call with the FDA.

Vowst isn’t the first FMT replacement pill to receive FDA approval. The agency approved Ferring Pharmaceuticals’ Rebyota, a fecal microbiota pill administered rectally in a single dose, in November. Both drugs outperform placebos in studies. Dr. Sahil Khanna, a gastroenterologist at the Mayo Clinic and an investigator on Vowst clinical trials, said it benefits patients to have both options. Khanna noted that some elderly C. diff patients have trouble swallowing, making Rebyota the better choice for them. Others with aversions to taking anything rectally may prefer Vowst.

Khanna sees Vowst and Rebyota, the first microbiota-based pills to receive FDA clearance, as indicators of how medicine is improving. “The bigger umbrella is microbiota restoration therapies,” he said. Khanna predicts microbiota-based therapeutics will expand to treat medical conditions such as inflammatory bowel disease and multidrug resistant infections.

While Khanna doesn’t see a need to steer completely away from FMT procedures, he noted that FMT’s reliance on stool banks is unsustainable. Stool banks are a hassle to maintain, and access is limited. The nonprofit OpenBiome, the largest U.S. stool bank, announced plans to phase out its FMT program in February 2022. In commenting on the Mayo Clinic’s stool bank, Khanna said, “It is so cumbersome to run and maintain it that I’m actually thinking it’s a welcome thing [to provide alternatives].”

Dr. Alexander Khoruts, a gastroenterologist and director of the Microbiota Therapeutics Program at the University of Minnesota, is less enthusiastic about the new pills. To make the Vowst pill, Seres washes human stool samples with ethanol to kill most bacteria. Only spore-forming Firmicute bacteria capable of surviving the ethanol treatment remain. Khoruts questions whether this purification process eradicates components of fecal microbiota that help repair the gut microbiome. He is concerned about the potential long-term effects of treatment with Vowst versus allowing nature to take its course with FMT.

While the spore-forming Firmicutes help repair the gut microbiome, Khoruts explained that the rest of the depleted gut bacteria would be replaced with bacteria from the patient’s environment. That’s not a good set-up for recurrent C. diff patients, who tend to be elderly and are frequently exposed to immunocompromised people due to frequent visits to the hospital or living in a nursing home. “That’s my safety concern—what happens over a year, a couple of years, when their microbiome is now reconstituted?” he said.

Dr. Darrell Pardi, a gastroenterologist at the Mayo Clinic, described concerns about Vowst’s efficacy as “theoretical” in an email to WORLD. Pardi explained that while medical experts don’t know what components of an FMT are required for effectiveness, “the results of the phase 3 study speak for themselves. The efficacy observed with SER-109 (Vowst) is about what we see with traditional FMT.”

Khoruts noted that both Vowst and Rebyota are more expensive than FMT. Vowst’s sticker price is $17,500 per course of therapy, while Rebyota’s is nearly $9,500.According to the American College of Gastroenterology, FMT costs between $500 and $1,500. He also highlighted that Rebyota’s manufacturing process starts with stool donations from paid donors. Khoruts thinks this presents a moral dilemma, as the potential to earn money may motivate donors to be dishonest about their medical history to prevent disqualification.