Patients treated with SER-109 reported a significant improvement in disease-specific health-related quality-of-life, regardless of their clinical outcome.
Recurrent Clostridioides difficile infection (CDI) is a debilitating disease that, if not fatal, causes diarrhea, fever, stomach pain, loss of appetite, and nausea. In addition to the uncomfortable and embarrassing physical symptoms, CDI patients often experience poor health-related quality of life, loss of productivity, anxiety, and depression.
About 20-36% of CDI patients experience a recurrence, and each recurrent CDI becomes more deadly and increases the risk of subsequent recurrences. There are drugs, such as fidaxomicin and vancomycin, that effectively kill C difficile spores. However, they are so powerful that they may actually further decimate the gut microbiome.
SER-109 is an oral investigational microbiome therapeutic designed to compete metabolically with C difficile and restore colonization resistance to C diff. SER-109 contains a consortium of highly purified Firmicutes spores, which populate a healthy gut microbiome.
SER-109 was proven to be safe and effective in numerous clinical trials, earning it a Prescription Drug User Fee Act (PDUFA) action date of April 26, 2023. A new study, however, wanted to determine whether treatment with SER-109 improved disease-specific health-related quality-of-life in adults with recurrent Clostridioides difficile infection.
The investigators conducted a secondary analysis of a randomized, double-blind, placebo-controlled, phase 3 clinical trial of 182 adults. The trial ran from July 2017-August 2020 and encompassed 56 sites across the US and Canada.
All trial participants were 18 years or older and had at least 3 CDI recurrences within a year. A previous episode of CDI was defined as:
(1) The presence of diarrhea (3 or more unformed bowel movements over 2 consecutive days)
(2) A positive C difficile toxin test
(3) Enzyme immunoassay or cell cytotoxicity neutralization assay, and resolution of symptoms following 10 to 21 days of standard of care therapy with vancomycin or fidaxomicin.
Before randomization, the participants were categorized by age (younger than 65 years or 65 years and older) and antibiotic treatment received (vancomycin or fidaxomicin). The 182 adult patients were randomly assigned to either SER-109 or placebo, after initial treatment with antibiotics.
After completing standard care antibiotics, patients were randomized 1 to 1 to receive 4 oral capsules of SER-109 (~3 × 107 spore colony-forming units) or matching placebo daily for 3 days. The patients were monitored for 8 weeks for CDI recurrence, defined as onset of 3 or more unformed bowel movements a day for 2 consecutive days, a positive C diff stool toxin assay, assessment by the investigators that antibiotic treatment was necessary, and/or diarrheal persistence until resuming antibiotic therapy.
The primary outcome of interest was the rate of CDI recurrence for up to 8 weeks after beginning SER-109 treatment. The investigators collected C diff measures at day 1 (baseline), week 1, week 8, or at the date of recurrence.
This secondary analysis found that patients treated with SER-109 saw significantly greater improvements in disease-specific health-related quality-of-life than the patients who received placebo. Notably, improvements in quality-of-life were distinct as early as week 1 of SER-109 treatment.
At week 1, the proportion of patients with overall improvement from baseline was 49.4% in the SER-109 group and 26.9% in the placebo group. At week 8, this rose to 66.3% improvement in the SER-109 group versus 48.4% in the placebo group.
In the placebo cohort, improvements in disease-specific health-related quality-of-life were primarily observed in patients with nonrecurrent CDI. However, SER-109 recipients reported improvements in disease-specific health-related quality-of-life regardless of their clinical outcome.
The investigators concluded that the investigational therapeutic SER-109 was associated with rapid and steady improvement in disease-specific health-related quality-of-life compared with placebo through 8 weeks of study. This is a vital outcome because patients have reported that restoration of quality-of-life is just as important, if not more so, than the clinical benefits of reduced CDI recurrence.