Oral treatment with freeze-dried human stool can successfully treat Clostridioides difficile infections by increasing the diversity of microorganisms in the colon, researchers say.

CP101, which is being developed by Finch Therapeutics, was shown to be more effective than placebo at preventing recurring infections for up to 24 weeks.

The CP101 capsules contain a powder made from freeze-dried human stool from screened donors. They are restoring the natural diversity disrupted by antibiotics, said Jessica Allegretti, MD, MPH, gastroenterologist at Brigham and Women’s Hospital in Boston, Massachusetts.

The treatment offers an alternative to fecal microbiota transplantation that can effectively treat antibiotic-resistant C-difficile infections but is difficult to standardize and administer – and does not have full approval from the U.S. Food and Drug Administration, she added.

“I think this is a moment in this area where we will have better, safer, and more available options for patients,” she told Medscape Medical News. “It is exciting.”

Allegretti is the author of three presentations of the results of PRISM3, a phase 2 study of CP101. They will be presented (also virtual) this week at the American College of Gastroenterology’s 2021 annual meeting in Las Vegas. These results extend over 24 weeks, while the 8-week results of this study were presented at the same meeting a year ago.

Study details

198 people who received antibiotics for recurring C-difficile infections took part in the study. Some patients had two or more relapses while others had only one relapse but were 65 years of age or older.

“It was a unique aspect of this study to see how a therapy like CP101 fits earlier into the treatment paradigm,” Allegretti said. “For an elderly, frail, or more fragile patient, you can imagine that you want to get rid of this [infection] previously.”

After waiting 2-6 days for the antibiotics to be washed out, the researchers randomly assigned 102 of these patients to take the CP101 tablets orally and 96 placebo tablets, both without bowel preparation.

The two groups did not differ significantly in terms of age, gender, comorbidities, the number of C-difficile recurrences, or the type of test used to diagnose the infection (PCR-based vs. toxin-EIA-based).

After 8 weeks, 74.5% of those who received the CP101 pills had no relapse compared with 61.5% of those who received the placebo. The difference was just about statistically significant (P = .0488).

Sixteen weeks later, the effects persisted, with 73.5% of the CP101 group and 59.4% of the placebo group still being recurrence-free. The statistical significance of the difference improved slightly (P = .0347).

Drug-related adverse events occurring were similar between the two groups: 16.3% for the CP101 group vs. 19.2% for the placebo group. These were mainly gastrointestinal symptoms and none were serious.

Some of the patients were given vancomycin as first-line treatment for C-difficile infections, and researchers wondered if the washout time was insufficient to remove this antibiotic, leaving enough to interfere with CP101’s effectiveness.

Therefore, they separately analyzed 40 patients treated with fidaxomicin, which they expected to wash out more quickly. Of these patients, 81% who received CP101 were recurrence-free at 8 weeks and 24 weeks. This compared to 42.1% of those who received the placebo at both time points. This difference was statistically more significant (P = .0211).

Understand how it works

To better understand how CP101 works, the researchers collected stool samples from the patients and counted the number of different types of organisms in each sample.

At baseline, patients were roughly the same number, but after one week the diversity was greater in the CP101-treated patients, and this difference had increased by week 8. The researchers also found much lower organism diversity in the stool of these patients who had relapsed C-difficile infection.

The variety of microbes in the successfully treated patients appeared to have been introduced by CP101. Allegretti and colleagues measured the number of organisms in the stool samples derived from CP101. They found that 96% of patients colonized with CP101 organisms had avoided recurrence of C-difficile infections, compared with 54.2% of patients who were not colonized by these microbes.

“We now have some microbial-based markers that show us as early as week 1 that the patient will be cured or not,” said Allegretti.

Based on these results, Finch plans to start a phase 3 study soon, she said.

The colonization data are interesting because they weren’t found in fecal microbiota grafts, said Purna Kashyap, MBBS, co-director of the microbiome program at Mayo Clinic College of Medicine in Rochester, Minnesota, who was not involved in the study.

But to better interpret the data, it would be helpful to know more about how the baseline placebo and CP101 groups compared for drugs, immunosuppression, and antibiotics used to treat C-difficile infections, Kashyap said. He was impressed with the lower cure rate in the fidaxomicin-treated part of the placebo group.

“Overall, I think these are exciting observations based on the data but require careful review of all of the data to make sense [them]what will happen if it goes through peer review, “he told Medscape Medical News in an email.

Several other standardized microbiota restoration products are under development, Medscape Medical News reports, including at least two more capsules. In contrast to CP101, which consists of a whole stool, VE303 (Vedanta Biosciences) is a “rationally defined bacterial consortium” and SER-109 (Seres Therapeutics) is a “consortium of highly pure Firmicutes spores”. VE303 has completed a phase 2 study and SER-109 has completed a phase 3 study.

Allegretti is an advisor to Finch Therapeutics, which funded the study. Kashyap has not disclosed any relevant financial relationships.

American College of Gastroenterology (ACG) 2021 Annual Scientific Meeting: Abstracts P0129 and P0130 will be presented on October 24, 2021 and Abstract 25 will be presented on October 26, 2021.

Laird Harrison writes about science, health and culture. His work has appeared in national magazines, newspapers, public radio and websites. He is working on a novel about alternative realities in physics. Harrison teaches writing at the Writers Grotto. Visit him at lairdharrison.com or follow him on Twitter @ LairdH

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