A post-hoc analysis of clinical trial data found a high cumulative cure rate after use of an oral microbiome therapeutic for recurrent Clostridioides difficile infection (CDI). The findings were presented at Digestive Disease Week (DDW), held from May 21 to 24, 2022 in San Diego, California, and virtually.
A key pathogenesis feature of recurrent CDI is disruption of the microbiome. Despite the role that the microbiome plays in CDI, to date there has been little evidence supporting the efficacy of a microbiome therapy.
The PRISM3 placebo-controlled trial found that patients with recurrent CDI who received CP101, an oral microbiome therapeutic designed to restore microbiome diversity, had a higher rate of sustained clinical cure compared with placebo. For this post-hoc analysis, data from PRISM3 and the open-label extension PRISM-EXT were evaluated. Patients (N=214) received the one-time CP101 oral therapy following standard-of-care antibiotics. The primary endpoint was sustained clinical cure at 8 weeks, as defined by no recurrence of CDI. Safety and efficacy were evaluated through week 24.
Patients who received CP101 in PRISM3 (n=102), placebo recipients in PRISM3 who received CP101 in PRISM-EXT (n=30), and PRISM-EXT direct entry participants (n=82) were aged median 69.0 (range, 19-97), 71.0 (range, 30-94), and 67.0 (range, 18-95) years; 68%, 73%, and 73% were women; 72%, 93%, and 48% had 3 or more CDI episodes; and average Charlson comorbidity index was 3.9 (standard deviation [SD], 2.9), 3.6 (SD, 2.6), and 3.0 (SD, 2.2), respectively.
At week 8, the cumulative cure rate was 85.0%. Among the subset of patients who received CP101 in PRISM3, 20 received a second CP101 dose during the extension period. The cumulative cure rate at 8 weeks among the patients who received active treatment in CP101 was 88.2%, which was higher than what was observed in the original trial (74.5%).
No treatment-related serious adverse events were reported through week 24.
“This is the largest reported dataset of an investigational orally administered microbiome therapeutic for recurrent CDI,” the researchers concluded.
Allegretti JR, Kelly CR, Fischer M, Cohen T, Budree S, Khanna S. Cp101, An Investigational Microbiome Therapeutic For The Prevention Of Recurrent C. Difficile Infection: A Combined Analysis Of The Prism3 (Randomized Placebo-Controlled) And Prism-Ext (Open-Label) Trials. Presented at: DDW 2022; May 21-24, 2022; San Diego, CA. Abstract Tu1519.