CDI Biotherapeutic RBX2660 Outperforms Placebo in Phase 3 Trial

New phase 3 data on a live biotherapeutic product for the treatment of recurrent Clostridioides difficile (C diff) infection (CDI) are strengthening the case that the product can lead to long-term positive results.

The therapy, RBX2660 (Rebyota), outperformed placebo in the new, phase 3, randomized, double-blinded study, which was published in the journal Drugs.

“These are extremely positive data and bring hope to our patients with recurrent CDI infection,” the study’s lead author, Sahil Khanna, MBBS, MS, told Contagion.

Between 15,000 and 30,000 people in the United States are believed to die each year as a result of CDI, and many patients who survive the infection will experience recurrences.

Antibiotics are considered the standard of care treatment for CDI, but they also have the downside of disrupting the gut microbiota, thereby increasing a patient’s risk of recurrence. An alternative strategy to antibiotics is fecal microbiota transplantation (FMT), a process by which normal microbiota of healthy donors is transplanted to infected patients in order to correct the patient’s microbiota disruption.

However, the treatment carries the risk of unintentionally transmitting harmful pathogens to patients with CDI, a concern that became even more poignant during the COVID-19 pandemic.

RBX2660 is an attempt to leverage the benefits of FMT while reducing the risks associated with the procedure. The therapy is made up of a broad consortium of live microbes taken from human stool samples and then rigorously screened for pathogens.

“This agent is different because it is produced in a standardized manner, with donor screening standardized, composition of numbers of bacteria standardized, and patient follow-up standardized,” said Khanna, a professor at the Mayo Clinic. He added that doses can also be traced back to donors.

In September, a Food and Drug Administration committee voted to recommend a biologics license application for the therapy.

In the new study, adults with one or more CDI recurrences and positive stool assays for C difficile who had already been treated with antibiotics were assigned to receive RBX2660 or placebo, on a 2:1 basis. A total of 267 people were enrolled, 180 of whom received RBX2660, while the rest received placebo.

The data was analyzed using a Bayesian analysis that incorporated data from a previous phase IIb study. The results suggested that 70.6% of patients receiving RBX2660 were successfully treated, compared with 57.5% of patients who received placebo. Moreover, 90% of patients who achieved success at 8 weeks had a sustained response that lasted at least 6 months, Khanna and colleagues found.

Patients receiving RBX2660 had higher rates of adverse events compared to people receiving placebo (55.6% versus 44.8%), though most of the adverse events in the RBX2660 group were mild or moderate gastrointestinal events. Two patients in the RBX2660 group died during the study’s follow-up period, though both deaths were deemed related to pre-existing conditions and were not believed to be the result of the treatment.

When FMT first emerged as a therapy, there was significant concern that patients would reject the treatment due to the fact that it was based on stool donations. However, Khanna said he has not seen problems with patient acceptance among people with recurrent infections, and he added that the standardized process behind RBX2660 also helps allay such concerns.

“I think microbiome based products which are getting standardized will be acceptable both by providers and patients going forward,” he said. “These are more standardized and have a track record for safety, more than currently acceptable fecal microbiota transplantation.”