Investigational Biotherapeutic Offers Relief From CDI Recurrence by “Filling in the Cracks” in the Microbiome

Abstracts presented at Digestive Disease Week 2022 showed that RBX2660, an investigational microbiota-based drug, was more likely to reduce the recurrence of Clostridioides difficile infection (CDI) compared with placebo.

The abstracts noted the substantial public health burden posed by CDI, which is exacerbated by its high morbidity and mortality rates and the frequency of recurrence within 8 weeks of a previous episode.

The explanation for recurrence, which occurs in about 35% of patients who receive a standard-of-care antimicrobial, is that the traditional therapy “only treats 1 of the 2 phases of C difficile, the so-called vegetative phase, or the phase that releases toxins that cause the symptoms,” Paul Feuerstadt, MD, of Yale University School of Medicine and PACT Gastroenterology Center, told The American Journal of Managed Care®.

“The spore phase is a phase that remains within the intestinal tract, specifically the colon of patients, and it’s up to the microorganisms or the bacteria in the microbiota within the colon for it to eradicate the infection,” Feuerstadt continued. “But the problem with C difficile is that that microbiota is deficient.”

Investigators are aiming to supplement the microbiome using microorganisms from a healthy person in the form of RBX2660, a pharmaceutically produced product that goes through donor screening, pathogen screening, and quality assurance before being given to patients with CDI, “so you’re supplementing the deficiencies but doing it in a much safer and efficient manner” compared with previous investigator-initiated studies of fecal microbiota transplantation, Feuerstadt explained.

One abstract presented by Feuerstadt and colleagues, a subgroup analysis of patients in the randomized, placebo-controlled PUNCH CD2 and PUNCH CD3 trials, looked at data from patients who received 1 dose of either RBX2660 or placebo in both studies.¹ Investigators aimed to determine the difference in the treatment success rate—defined as remaining recurrence-free for 8 weeks post treatment—between the RBX2660 (n = 221) and placebo (n = 131) groups.

Overall, the rate of treatment success in this pooled analysis was higher in those receiving RBX2660 compared with placebo (68.3% vs 55.0%; P = .012). The difference in the treatment success rates did not differ significantly by patient age, sex, race, ethnicity, site location, number of previous CDI episodes, or duration of antibiotic use prior to study participation.

When presenting the results at a conference session on Tuesday, Feuerstadt made sure to thank the patients who took part in the trials and their caregivers, “because without their participation in these clinical trials, we would not be able to understand our patients and our patients’ pathophysiology, but more importantly, interventions of how we can help larger groups of individuals.”

Another poster analyzed data from the PUNCH CD3 trial on patients with documented recurrent CDI who had received standard-of-care antibiotic therapy prior to receipt of RBX2660 or placebo.² Investigators calculated the time to CDI recurrence, defined as the number of days from study treatment to the first assessment indicating a CDI event.

They found that CDI recurrence was most common within the first 2 weeks after treatment with either placebo or RBX2660. However, Kaplan-Meier curves revealed that recurrence tended to occur earlier in participants who received placebo vs RBX2660, and the 25th percentile of the Kaplan-Meier estimate for time to recurrence was 14 days for placebo and 30 days for RBX2660.

Additionally, the overall cumulative probability of CDI recurrence at 8 weeks was lower in participants who received RBX2660 (27%) than in those who received placebo (35%).

REFERENCES

1. Feuerstadt P, Assi M, Braun T, Su X. RBX2660 versus placebo to reduce the recurrence of Clostridioides difficile infection: subgroup analysis. Presented at: Digestive Disease Week; May 21-24, 2022; San Diego, CA. Presentation 892.

2. Khanna S, Kao DH, Lee C, Ando M, Su X, Braun T. Time to recurrence in patients with clostridioides difficile infection treated with placebo or RBX2660. Presented at: Digestive Disease Week; May 21-24, 2022; San Diego, CA. Abstract Su1608.