For those battling Clostridium difficile infection, which causes diarrhea, Fecal Microbiota Transplantation (FMT) offers a proven solution, although it can be overwhelming. Feces from healthy donors — often excreted through colonoscopy — can help restore intestinal flora balance, eliminating potentially fatal infections. Several companies are eager to achieve the same effect with less invasive, more standardized therapies that could be approved by U.S. regulators. One option is the drug SER-109, which contains bacterial spores isolated from human feces, which has now successfully conducted a phase III trial that paves the way for the first approval of a similar drug.
FMT can break the cycle of repeated infections in Clostridium difficile, which is common in older patients with other health problems, usually starting when antibiotics deplete their normal microbiota. Sahlil Khanna, a gastroenterologist at the Mayo Clinic who participated in the SER-109 trial, said FMT has been part of mainstream medicine for 10 years, but transplant materials from volunteer guts are difficult to standardize.
The new pill, called SER-109, is produced by Seres Therapeutics, which is extracted from purified human feces with the aim of screening microbes in the body. Pre-screened donor feces are treated with ethanol, which kills many viruses, fungi, and "vegetative" bacteria in a state of growth and reproduction. Bacteria left behind after treatment can form strong, thick-walled structures called spores. These bacteria are valuable because they can compete with Clostridium difficile in the gut. "It can take up space, food and carbon sources for Clostridium difficile." Lisa von Moltke, chief medical officer at Seres Therapeutics, notes that the bacteria also alter the composition of bile acids in the gut, making the environment less friendly to Clostridium difficile.
Vincent Young, a microbiologist at the University of Michigan in Ann Arbor who was not involved in the new trial, said Seres Therapeutics' purification process was designed to remove most of the pathogens known to pose a safety risk to patients. "There are no data yet, but there is reason to think that SER-109 is safer than feces."
It is understood that the SER-109 Phase III trial recruited 182 participants infected with Clostridium difficile, who were randomly divided into SER-109 and placebo after a standard course of antibiotics, of which 149 completed an 8-week follow-up. Recently, researchers reported in the New England Journal of Medicine that the proportion of recurrence of Clostridium difficile infection in the placebo group was 40%, compared with only 12% in the SER-109 group.
Colleen Kelly, a gastroenterologist at Brown University, said the results can be compared to those of FMT. Many patients want to avoid the discomfort of colonoscopy, she said, and if there are other options, they opt for medications.
Some researchers have expressed doubts about whether the new treatment can match the efficacy of the intact fecal microbiota. Alexander Khoruts, a gastroenterologist at the University of Minnesota-Twin Cities, noted that the fecal components that Seres Therapeutics removes during the purification process, including bacteria-killing viruses known as bacteriophages, could be critical to FMT's success. "I'm satisfied that SER-109 is more effective than a placebo, but I don't believe the other ingredients are negligible," he said.
Seres Therapeutics plans to submit an application for approval of SER-109 to the U.S. Food and Drug Administration in 2022. (Bunraku)
Source: China Science Daily