The first FDA-approved fecal microbiota product maintained a positive safety profile in the largest safety evaluation to date with up to 2 years of safety data.
Rebyota, Ferring Pharmaceutical’s fecal microbiota treatment for recurrent Clostridioides difficile infection (rCDI), was found to be safe and tolerable in the largest safety study of a microbiota-based biotherapeutic.
The study, published in Therapeutic Advances in Gastroenterology, included safety data from 5 prospective clinical trials – 3 phase 2 and 2 phase 3 – involving about 1000 adults with documented rCDI.
“This integrated safety analysis is the largest safety evaluation to date of any microbiota-based live biotherapeutic and includes safety data for up to 2 years,” Lindy Bancke, PharmD, vice president of global clinical operations, US, for Ferring Pharmaceuticals, told Contagion®. “It is important to understand the safety and tolerability of Rebyota across a broad patient population seen in clinical practice, and this analysis builds upon that data.”
The FDA approved the drug RBX2660, marketed under the brand name Rebyota, to prevent recurrent CDI in November, making it the first FDA-approved fecal microbiota product. Rebyota is made up of a consortium of fecal bacteria from healthy donors and administered rectally following standard-of-care antibiotic treatment.
“As the first FDA-approved microbiota-based treatment for the prevention of recurrence of C diff infection in individuals 18 years of age and older, following antibiotic treatment for recurrent C diff infection, much of our development work was truly pioneering since there was no precedent for an approval of this type in the field,” Bancke said. “However, a program in this field containing 5 prospective clinical trials, nearly 1000 patients, and up to 2 years of safety data is substantial and groundbreaking.”
The study included 978 patients who received Rebyota, with 620 receiving 1 dose, 332 receiving 2 doses, 14 receiving 3 doses and 12 receiving 4 doses. The study also included 83 participants who received placebo only.
Most of the participants in the treatment group – about 80% – had 3 or more prior CDI occurrences, and about half were older than 65, highlighting the dangers of the disease, which can lead to sepsis, colectomy, and death.
Treatment-emergent adverse events, including abdominal pain, nausea, and flatulence, were reported in 66.4% of those who received Rebyota compared with 60.2% of those who received the placebo. Only 3% of participants experienced potentially life-threatening TEAEs. No reports of infections caused by the treatment were noted.
“As part of the largest safety analysis to date, containing patient data up to two years, it is notable that most treatment-emergent adverse events were mild or moderate in severity and were most frequently related to pre-existing conditions,” Bancke said. “There were no unexpected TEAEs reported, and the data consistently demonstrated the safety and tolerability of Rebyota in adults.”
The risk of sepsis or bacteremia was less than 1% among those treated with Rebyota compared with 27% of patients aged 18 to 64 and 35% of those older than 65 with one rCDI bout who experienced sepsis within 12 months of initial infection.
Rigorous screening and manufacturing protocols help ensure that pathogens aren’t introduced through the treatment.
“We continue to look at broader, real-world patient populations that are seen in clinical practice,” Bancke said. “In addition, we are looking at disease areas beyond recurrent C diff infection. The link, between the gut microbiome and human health, presents an opportunity for developments that address unmet needs and advance patient care.”