*EMBARGOED All research presented at the 2021 ACG Annual Scientific Meeting and Postgraduate Course is strictly embargoed until Sunday, October 24, 2021, at 3:30 pm EDT.
Oral 25 CP101, an Investigational Orally Administered Microbiome Therapeutic, Increases Intestinal Microbiome Diversity and Prevents Recurrent C. difficile Infection: Results From a Randomized, Placebo-Controlled Trial
Author Insight from Jessica R. Allegretti, MD, MPH, FACG, Brigham and Women’s Hospital
What’s new here and important for clinicians?
Clostridioides difficile infection (CDI), one of the most common healthcare-associated infections, is a debilitating and sometimes life-threatening disease that is characterized by severe diarrhea. Recurrent CDI is common following standard-of-care (SOC) antibiotics used to treat active CDI. SOC antibiotics can significantly disrupt the intestinal microbiome. Disruption of the intestinal microbiome impairs colonization resistance, or the ability of a healthy microbiome to inhibit the colonization and expansion of pathogens such as C. difficile, which can put patients at risk for recurrent CDI. There is a significant unmet need for FDA-approved therapeutics that restore the microbiome following SOC antibiotics and enable early intervention to prevent recurrent CDI. CP101 is an investigational, orally administered, complete microbiome therapeutic designed to enable prevention of recurrent C. difficile infection by restoring a diverse microbial community and key physiological pathways, which contributes to colonization resistance
We conducted a Phase 2, double-blind, randomized, placebo-controlled, multi-center trial (PRISM3) enrolling adults who received SOC antibiotics for recurrent CDI followed by CP101 or placebo. Following SOC CDI antibiotics, 74.5% of participants treated with CP101 in PRISM3 achieved sustained clinical cure (defined as absence of CDI), a statistically significant improvement over those receiving placebo (61.5%; p<0.05), meeting the primary efficacy endpoint and representing a clinically meaningful 33.8% relative risk reduction for CDI recurrence. Furthermore, there were no treatment-related serious adverse events (SAEs) in the CP101 arm. The PRISM3 data presented provide important insights into the mechanism of action of CP101.
- The data show that one-time administration of CP101 resulted in engraftment of CP101-associated taxa. Engraftment is defined as the presence of product-specific microbes that colonize the gastrointestinal tract, and is a key pharmacokinetic marker of microbiome therapeutics. Engraftment at week 1 was significantly associated with sustained clinical cure at week 8.
- Patients with CDI have a disrupted microbiome including significantly lower diversity compared with healthy individuals. One-time administration of CP101 resulted in a rapid and sustained increase in microbiome diversity, a key pharmacodynamic marker of microbiome therapeutics. Increase in microbiome diversity at Week 1 was significantly associated with sustained clinical cure at Week 8, demonstrating that increased diversity enhances colonization resistance leading to sustained clinical cure at 8 weeks. PRISM3 is the first positive RCT of an orally administered investigational microbiome therapeutic that included patients enrolled after their first CDI recurrence and patients diagnosed with CDI at study entry by any guideline recommended test method. The broad PRISM3 patient population increases the generalizability of the results to real-world clinical practice and provides robust data to support the future potential use of CP101 as early as first CDI recurrence. These robust pharmacological and clinical results will be further evaluated in PRISM4, a global, Phase 3 clinical trial.
What do patients need to know?
Antibiotic use can put individuals of any age at increased risk of C. difficile (C. diff), an infection that can cause debilitating and sometimes life-threatening diarrhea.
Antibiotics can significantly disrupt the microbiome, the community of microbes that live on and within the human body and play an important role in human health. Disruption of the microbiome impairs the body’s ability to fight off pathogens, such as C. diff.
Treatment options for recurrent (repeated) C. diff are currently limited, with no FDA-approved microbiome therapies available for recurrent C. diff. Each episode of C. diff increases the risk of another recurrence, which can trap patients in repeated cycles of C. diff. Breaking the cycle of recurrence is key to preventing the suffering associated with recurrent C. diff.
CP101 is an investigational, orally administered microbiome therapeutic designed to prevent recurrent C. diff and enable early intervention in the management of C. diff. CP101 is delivered in a one-time administration of capsules, without the need for a bowel prep.
In the PRISM3 clinical trial, participants with recurrent C. diff who received CP101 after completing a round of antibiotics were significantly less likely to experience another episode of C. diff, compared to patients who received antibiotics plus a placebo. In the trial, 74.5% of patients who received CP101 achieved a clinical cure, meaning they did not experience a recurrence of C. diff within 8 weeks of taking CP101.
The efficacy and safety of CP101 for the prevention of recurrent C. diff will be further evaluated in PRISM4, a global, Phase 3 clinical trial. References: CDC Antibiotic Resistance Threat Report 2019 (https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf) Kelly CP. Can we identify patients at high risk of recurrent Clostridium difficile infection? Clin Microbiol Infect. 2012 Dec
Jessica R. Allegretti, MD, MPH, FACG, Brigham and Women’s Hospital
jallegretti [at] bwh [dot] harvard [dot] edu
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