Phase 3 Study Shows Live Biotherapeutic Significantly Reduces CDI Recurrence

Ferring’s RBX2660 was shown to be safe and significantly reduce recurrence of Clostridioides difficile infection (CDI) after standard-of-care antibiotic treatment over 8 weeks, with a sustained response achieved through 6 months.

Recurrent CDI (rCDI) is associated with a significant burden for caregivers and the health care system, with the public health impact of the infection totaling as much as $4.8 billion due to extended length of stay and associated costs in acute care facilities.

RBX2660, an investigational microbiota-based live biotherapeutic consisting of a broad consortium of microbes prepared from human stool, has previously demonstrated safety and efficacy in 6 studies that were included in the biologics license application (BLA) for the drug.

Following these findings, an FDA advisory committee issued a positive vote for its potential in reducing rCDI after antibiotic treatment among adults 18 years of age and older.

Data published recently in Drugs provided additional efficacy and safety data from the phase 3, randomized, double-blind, placebo-controlled PUNCH CD3 trial (NCT03244644), which used a Bayesian primary analysis integrating data from the previous Phase 2b study (PUNCH CD2).

RBX2660 was assessed in adults who had 1 or more CDI recurrences with a positive stool assay who were previously treated with antibiotics. Participants were randomly assigned 2 to 1 to receive a subsequent blinded, single-dose enema of RBX2660 or placebo. The primary endpoint was treatment success, defined as the absence of CDI diarrhea within 8 weeks of study treatment.

A total of 320 patients were screened, of which 289 were randomly assigned and 267 received blinded treatment (n = 180, RBX2660; n = 87, placebo). Participants primarily were female (68.5%) and White (92.1%), with a median age of 63 years (range, 19–93). The model-estimated treatment success rate at 8 weeks were 70.4% vs 58.1% with RBX2660 and placebo, respectively.

After aligning the data to improve the exchangeability and interpretability of the Bayesian analysis, the model-estimated treatment success rate was 70.6% with RBX2660 vs 57.5% with placebo, with an estimated treatment effect of 13.1% and a 99.1% posterior probability that RBX2660 was superior to placebo in reducing rCDI after standard-of-care antibiotic treatment.

Furthermore, greater than 90% of the participants who achieved treatment success at 8 weeks had sustained response through 6 months in both the RBX2660 and the placebo groups.

RBX2660 was indicated to be well tolerated overall, with manageable adverse events. Incidence of treatment-emergent adverse events was higher in RBX2660 recipients compared with placebo (55.6%, n= 100, RBX2660; 44.8%, n = 39, placebo), and was mostly driven by a higher incidence of mild gastrointestinal events.

Study authors noted that the small number of non-White participants and the lack of participants with irritable bowel syndrome and inflammatory bowel disease, and immunocompromised patients limit the ability to broadly generalize these data. However, an open-label study (PUNCH CD3-OLS) is ongoing, which they said includes a more diverse rCDI population compared with prior RBX2660 studies.

“The findings from this Phase 3 trial provide hope that this potential treatment could make a meaningful difference in the lives of patients with rCDI,” said lead study author Sahil Khanna, MBBS, MS, a gastroenterologist and hepatologist who leads Mayo Clinic's clinical and research program involving fecal microbiota transplantation for CDI, in a statement.

Reference

Khanna S, Assi M, Lee C, et al. Efficacy and safety of RBX2660 in PUNCH CD3, a phase III, randomized, double‑blind, placebo‑controlled trial with a Bayesian primary analysis for the prevention of recurrent Clostridioides difficile infection. Drugs. Published online October 26, 2022. doi:10.1007/s40265-022-01797-x