An easy-to-administer oral biologic kept repeat C difficile infections at bay in a new study.
A recent study yielded encouraging results for a therapeutic biological drug that takes aim at recurrent C difficile infection (CDI). CDI is the most common cause of antibiotic-associated diarrhea and is a particular scourge in nursing homes and other healthcare facilities serving older adults. It’s typically treated with antibiotics, but frequent recurrences are not uncommon, and the most serious cases can be fatal.
The study team, led by Jessica Allegretti, MD, MPH, at Brigham and Women’s Hospital in Boston, tracked data on 132 individuals enrolled in the phase 2 PRISM-EXT trial. Participants hailed from 51 different sites across North America, and all had experienced at least 1 episode of recurrent CDI for which they received standard of care antibiotics followed by the microbial therapeutic drug CP101. The administration of CP101 was open label. The study’s primary endpoints were safety and the percentage of participants experiencing no CDI recurrence.
The results, revealed at the 2022 American College of Gastroenterology conference, show that CP101 was associated with reduced rates of recurrent CDI. Eight weeks after being treated, 80.3% of participants had not experienced CDI recurrence. By week 24, 78.8% had no CDI recurrence.
The study’s authors noted that CP101 resulted in increased engraftment of drug-associated taxa and diversity of the subjects’ microbiota from baseline to weeks 8 and 24, which was the hoped-for outcome. “It’s designed to deliver a diverse microbial community,” Allegretti said. In the case of the 26 participants who experienced a CDI recurrence prior to week 8 and the 2 who experienced a CDI recurrence between week 8 and week 24, the microbiome analysis may have been affected by the standard of care antibiotics they would have received.
The PRISM-EXT trial’s safety results were in line with those of earlier study results. No subjects experienced serious adverse events or death, and fewer than 1 out of 10 (9.8%) had any treatment-related adverse events. The most common adverse events were mild to moderate gastrointestinal symptoms.
Currently, the study team is enrolling patients in the phase 3 trial for CP101, with the goal of advancing the therapy toward FDA approval. Currently, there is a significant unmet need for FDA-approved oral CDI treatments that can restore a patient’s microbiome after CDI. While the medical community has embraced fecal microbiota transplantation (FMT) as an effective treatment for recurrent CDI, it’s considered an experimental procedure and is not FDA approved. In FMT, stool from healthy donors is administered to patients in order to colonize their gut, restoring diversity and balance. The processed stool is received either via the colon, through nasogastric tubes, or orally in capsules.
Allegretti pointed out that CP101 offers advantages over other therapies designed to work against CDI: It can be taken as a 1-time oral dose and requires no bowel prep. “Having a therapy like CP101 is going to be a real game changer to treat people with this difficult disease,” she stated. “We really have a good handle on the mechanism of action of this drug. I’m really excited to see the results of this phase 3 trial.”