RBX2660 Demonstrates Safe, Effective Results Treating Recurrent Clostridioides difficile Infection

RBX2660 demonstrated safe and effective results in reducing recurrent Clostridioides difficile infection (CDI) following standard-of-care antibiotics with a sustained response through 6 months, according to the results of a study published in Drugs.¹

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RBX2660 is an investigational live biotherapeutic product comprised of a broad consortium of microbes prepared from human stool for the reduction of recurrent CDI.¹

In the phase 3 PUNCH CD3 study (NCT03244644), investigators included adults who had 1 or more CDI recurrence with a positive stool assay and who were treated with standard-of-care antibiotics. The individuals were randomized 2:1 to receive either RBX2660 or a placebo. Investigators screened individuals between July 2017 and February 2020 at 44 sites in the United States and Canada.¹

The primary endpoint of the study was treatment successes measured by the absence of CDI diarrhea within 8 weeks of the study treatment. The study also used data from a previous phase 2b trial, PUNCH CD2.¹

In PUNCH CD2, the baseline patient microbiomes were similar in all the response groups, with a larger shift in responders to RBX2600 compared with non-responders. The microbiome changes were seen for up to 60 days.²

Of the 320 patients who were screened, 180 received RBX2660 and 87 received the placebo. In the original model estimates, the study authors said that the treatment success was 70.4% and 58.1%, respectively.¹

However, a Bayesian analysis found that the model-estimated treatment success rate was 70.6% for RBX2660 and 57.5% for the placebo. There was an estimated treatment effect of 13.1% and a posterior probability of superiority of 0.991. Investigators reported that more than 90% of those who had achieved treatment success at 8 weeks had sustained response through 6 months in both RBX2660 and the placebo groups.¹

Investigators gave 65 individuals a second treatment course following confirmed treatment failure. Of the 24 individuals who received the blinded placebo and were then treated with open-label RBX2660, 62.5% achieved treatment success within 8 weeks, which was sustained through 6 months.¹

Among 41 individuals treated with the blinded RBX2660 and then treated with the open-label drug, 53.7% achieved treatment success within 8 weeks. Of the individuals who had success, 86% were able to sustain the response over 6 months.¹

For safety, RBX2600 was generally well tolerated and had manageable adverse events (AEs). The incidence of treatment-emergent AEs was higher with the drug, which was driven by the greater incidence of mild gastrointestinal events, according to the results of the study. One individual discontinued treatment because of AEs.¹

Limitations of the study included the small number of non-White individuals enrolled as well as those with irritable bowel syndrome and inflammatory bowel disease. There was also a lack of immunocompromised individuals.¹

The study authors will continue to investigate the drug in PUNCH CD3-OLS, which is ongoing, and allows the enrollment of individuals who are immunocompromised or who have chronic conditions.¹

References

1. Khanna S, Assi M, Lee C, Yoho D, 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. 2022;82(15):1527-1538. doi:10.1007/s40265-022-01797-x
2. Khanna S, Blount K, Jones C, Shannon B, Carter S. Successful response to microbiota-based drug RBX2660 in patients with recurrent Clostridium difficile infection is associated with more pronounced alterations in microbiome profile. Open Forum Infect Dis. 2017;4(Suppl 1):S387. doi:10.1093/ofid/ofx163.963