Research Highlights Effect of New Biotherapeutic on Clostridioides difficile Infection

At IDWeek 2021, Ferring Pharmaceuticals and Rebiotix Inc presented a new data analysis of 5 prospective studies of the late-stage microbiota-based live biotherapeutic RBX2660, as well as the findings of the PUNCH CD3 phase 3 trial on the same topic. The treatment is being investigated for the reduction of recurrent Clostridioides difficile infection (rCDI).

In one abstract presented at the conference, Ferring and Rebiotix outlined the effects of RBX2660—a microbiota-based investigational live biotherapeutic—on colonization of antimicrobial-resistant (AMR) pathogens in the gut.

The PUNCH CD3 phase 3 trial of RBX2660 for rCDI showed participants’ AMR gene content decreased after RBX2660 treatment and remained low for at least 6 months, authors from Ferring and Rebiotix presented at IDWeek 2021.

These findings are consistent with those of prior RBX2660 trials and underscore the potential of microbiota-based biotherapeutics for removing AMR bacteria from gut microbiota, thereby reducing the risk of AMR infection and rCDI, they noted.

The investigators explained that intestinal colonization by AMR pathogens is a known health and infection risk that is common among individuals with rCDI.

“Accordingly, therapeutic approaches that decolonize the gut of AMR pathogens could be valuable to patients to reduce risk of associated illnesses,” they added.

In a blind study, patients with rCDI who enrolled in the PUNCH CD3 trial received either a single dose of RBX2660 or placebo within 24 to 72 hours after completing antibiotic treatment for their most recent rCDI episode.

“Clinical response was the absence of CDI recurrence at 8 weeks after treatment, and participants were asked to submit stool samples prior to RBX2660 or placebo treatment (baseline) and 1, 4 and 8 weeks, 3 and 6 months after study treatment.”

Clinically, RBX2660 showed superior efficacy vs placebo, at 70.4% vs 58.1%, respectively.

“Among genes that decreased in RBX2660 responders were clinically important extended-spectrum beta-lactamase (blaTEM, blaSHV, blaCTX-M), vancomycin resistance (vanA, vanB), and fluoroquinolone resistance genes (gyrA, parC),” the investigators wrote.

Another abstract by Ferring and Rebiotix summarized the findings of 5 prospective clinical studies on the efficacy of RBX2660 on individuals with CDI.

Among 629 participants across 5 trials, RBX2660 consistently reduced the recurrence of rCDI, with treatment success (TS) rates ranging from 50% to 78.9%.

The analysis included 3 phase 2 trials (PUNCH CD, PUNCH CD2, and PUNCH CD Open Label) and 2 phase 3 trials (PUNCH CD3 and PUNCH CD3-OLS ad hoc analysis).

All participants were 18 years or older, had documented rCDI, and completed standard-of-care (SOC) oral antibiotic therapy prior to RBX2660 treatment. Each participant received either 1 or 2 doses of RBX2660 or placebo, depending on the trial. TS was defined as “remaining recurrence-free for 8 weeks after treatment,” according to the abstract.

“Microbiota-based treatments have shown promise to reduce recurrence, morbidity, and mortality for [rCDI], but consistent and reliable clinical efficacy data are needed to support regulatory approvals that broaden patient access,” the investigators wrote.

Patients who responded to the treatment were monitored for additional recurrence for at least 6 months after the last dose. Treatment nonresponders received SOC antibiotic therapy and/or additional RBX2660 treatment and were monitored for recurrence for 8 weeks after the last dose. If the patient did not initially respond to the RBX2660 dose, the researchers did not rule out the potential clinical benefit of additional RBX2660 treatment.

The majority of patients who received the treatment remained CDI free for at least 6 months and up to 24 months, with TS rates between 74.4% and 92.1%. Additional RBX2660 treatments for primary nonresponders further reduced rCDI recurrence and overall TS rates ranged from 75.0% to 84.4%.

Among PUNCH CD, CD3, and CD3-OLS, a majority of primary responders remained CDI free to 6 and up to 24 months with success rates ranging from 74.4% to 92.1%.

“Collectively, these data demonstrate consistency and reliability of the potential benefit of RBX2660 across an entire clinical program,” the investigators concluded.

References

1. Hau H, Walsh DM, Gonzalez C, Shannon B, Blount K. Antimicrobial resistance genes were reduced following administration of investigational microbiota-based live biotherapeutic RBX2660 to individuals with recurrent Clostridioides difficile infection. Abstract presented at: 10th Annual IDWeek; September 29, 2021. Abstract 129.

2. Bancke L, Su X. Efficacy of investigational microbiota-based live biotherapeutic RBX2660 in individuals with recurrent Clostridioides difficile infection: data from five prospective clinical studies. Abstract presented at: 10th Annual IDWeek; September 29, 2021. Abstract 167.