Largest Integrated Safety Analysis From Five Prospective Clinical Trials for REBYOTA® (fecal microbiota, live – jslm) Published in Therapeutic Advances in Gastroenterology
- Integrated analysis is the largest safety evaluation to date of any microbiota-based live biotherapeutic and includes safety data for up to two years
- REBYOTA is indicated for the prevention of recurrence of Clostridioides difficile (C. diff) infection in individuals 18 years of age and older, following antibiotic treatment for recurrent C. diff infection
Parsippany, NJ, USA – July 11, 2023 – Ferring Pharmaceuticals today announced that Therapeutic Advances in Gastroenterology has published an integrated safety analysis from five prospective clinical trials for REBYOTA® (fecal microbiota, live – jslm), the first and only single-dose, FDA approved microbiome-based treatment to prevent recurrent C. diff infection after antibiotic treatment. The analysis, which includes data from about 1,000 clinical trial participants, is the largest safety evaluation to date of any microbiota-based live biotherapeutic and includes safety data for up to two years.1
“The integrated analysis provides further evidence that REBYOTA is a safe and well-tolerated treatment for patients with recurrent C. diff infection,” said Paul Feuerstadt, M.D., F.A.C.G., A.G.A.F., Yale University School of Medicine, and one of the analysis authors. “It is important to understand the safety and tolerability of REBYOTA across a broad patient population seen in clinical practice.”
The integrated safety analysis included three Phase 2 trials (PUNCH CD, PUNCH CD2, PUNCH Open-Label) and two Phase 3 trials (PUNCH CD3, PUNCH CD3-OLS) of REBYOTA. PUNCH CD3-OLS is still ongoing. Trial participants were at least 18 years of age with documented recurrent C. diff infection who completed standard-of-care antibiotic therapy before treatment with REBYOTA. Depending on the trial design, the assigned study treatment regimen was one or two doses of REBYOTA (or placebo) administered rectally. In four of the five trials, participants with recurrent C. diff infection within eight weeks after REBYOTA or placebo administration were eligible for treatment with open-label REBYOTA. Treatment-emergent adverse events (TEAEs) were recorded for at least six months following the last study treatment.1
Among the five trials, 978 participants received at least one dose of REBYOTA (assigned treatment or after recurrence) and 83 participants received placebo only. At six months, TEAEs were reported in 66.4% of REBYOTA-only participants (507 of 763; participants who received multiple doses of REBYOTA or who received placebo and REBYOTA were not included in this analysis) and 60.2% of placebo-only participants (50 of 83). There were no trial discontinuations for TEAEs related to REBYOTA or its administration in the Phase 3 trials. The most commonly reported TEAEs through six months were diarrhea (REBYOTA, 21.2%; placebo, 18.1%), abdominal pain (REBYOTA, 15.1%; placebo, 8.4%) and nausea (REBYOTA, 8.4%; placebo, 3.6%). Most TEAEs were mild or moderate in severity and were most frequently related to preexisting conditions. Serious TEAEs were mostly related to preexisting conditions (10%). Less than one percent (0.7%) of participants experienced a serious TEAE attributed as possibly related to REBYOTA and potentially life-threatening TEAEs were reported in 3% of participants.1
In the PUNCH CD2 and PUNCH Open-Label trials, TEAEs and serious TEAEs were collected through 12 and 24 months, respectively. A higher percentage of participants in the REBYOTA-only group (99 of 176, 56.3%) than in the placebo-only group (9 of 19, 47.4%) had at least one TEAE between six and 24 months after administration of the first dose of the most recent treatment course, with mild and moderate events accounting for the difference; however, this comparison is limited by the small number of participants in the placebo-only group who had two years of follow-up. Across treatment groups, most TEAEs were related to preexisting conditions; two TEAEs (0.9%) were related to REBYOTA. Serious TEAEs were reported in 29% (51 of 176) of participants in the REBYOTA-only group and in 31.6% (6 of 19) of participants in the placebo-only group. Across all treatment groups, serious TEAEs were considered related to C. diff infection or preexisting conditions, and none were considered related to REBYOTA or its administration.1
About C. diff infection
C. diff infection is a serious and potentially deadly infection that impacts people across the globe. The C. diff bacterium causes debilitating symptoms, such as severe diarrhea, fever, stomach tenderness or pain, loss of appetite, nausea and colitis (an inflammation of the colon).2 C. diff infection can be the start of a vicious cycle of recurrence, causing a significant burden for patients and the healthcare system.3,4 It has been estimated that up to 35% of C. diff infection cases recur after initial diagnosis and people who have had a recurrence are at significantly higher risk of further infections.5,6,7,8 After the first recurrence, it has been estimated that up to 65% of patients may develop a subsequent recurrence.7,8 Antibiotics – the current standard of care for treatment of C. diff infection – treat the disease but can also be a contributing factor to the cycle of recurrence.2
REBYOTA is a pre-packaged, single-dose 150 mL microbiota suspension for rectal administration consisting of a liquid mix of up to trillions of live microbes – including Bacteroides. REBYOTA is delivered directly to the gut microbiome and is administered by a healthcare professional in one visit.
REBYOTA (fecal microbiota, live – jslm) is indicated for the prevention of recurrence of Clostridioides difficile infection (CDI) in individuals 18 years of age and older, following antibiotic treatment for recurrent CDI.
Limitation of Use
REBYOTA is not indicated for treatment of CDI.
IMPORTANT SAFETY INFORMATION
Do not administer REBYOTA to individuals with a history of a severe allergic reaction (e.g., anaphylaxis) to any of the known product components.
Warnings and Precautions
Transmissible infectious agents
Because REBYOTA is manufactured from human fecal matter, it may carry a risk of transmitting infectious agents. Any infection suspected by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Ferring Pharmaceuticals Inc.
Management of acute allergic reactions
Appropriate medical treatment must be immediately available in the event an acute anaphylactic reaction occurs following administration of REBYOTA.
Potential presence of food allergens
REBYOTA is manufactured from human fecal material and may contain food allergens. The potential for REBYOTA to cause adverse reactions due to food allergens is unknown.
The most commonly reported (≥3%) adverse reactions occurring in adults following a single dose of REBYOTA were abdominal pain (8.9%), diarrhea (7.2%), abdominal distention (3.9%), flatulence (3.3%), and nausea (3.3%).
Use in Specific Populations
Safety and efficacy of REBYOTA in patients below 18 years of age have not been established.
Of the 978 adults who received REBYOTA, 48.8% were 65 years of age and over (n=477), and 25.7% were 75 years of age and over (n=251). Data from clinical studies of REBYOTA are not sufficient to determine if adults 65 years of age and older respond differently than younger adults.
You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.FDA.gov/medwatch, or call 1-800-332-1088.
Please click here for full Prescribing Information.
About Ferring Pharmaceuticals
Ferring Pharmaceuticals is a research-driven, specialty biopharmaceutical group committed to helping people around the world build families and live better lives. In the United States, Ferring is a leader in reproductive medicine and maternal health, uro-oncology and in specialty areas within gastroenterology, including microbiome therapeutics, and orthopaedics. For more information, call 1-888-FERRING (1-888-337-7464) or visit http://www.ferringusa.com/.
For more information, please contact:
Director, Brand Communications
- Lee C, Louie T, et al. Safety of fecal microbiota, live – jslm (REBYOTA™) in individuals with recurrent Clostridioides difficile infection: data from five prospective clinical trials. Ther Adv Gastroenterol. 2023;16:1-16. doi:10.1177/17562848231174277.
- Centers for Disease Control and Prevention. What Is C. Diff? 17 Dec. 2018. Available at: https://www.cdc.gov/cdiff/what-is.html.
- Centers for Disease Control and Prevention. 24 June 2020. Available at: https://www.cdc.gov/drugresistance/pdf/threats-report/clostridioides-difficile-508.pdf.
- Feuerstadt P, et al. J Med Econ. 2020;23(6):603-609.
- Riddle DJ, Dubberke ER. Clostridium difficile infection in the intensive care unit. Infect Dis Clin North Am. 2009;23(3):727-743.
- Nelson WW, et al. Health care resource utilization and costs of recurrent Clostridioides difficile infection in the elderly: a real-world claims analysis. J Manag Care Spec Pharm. 2021;27(7):828-838. doi: 10.18553/jmcp.2021.20395. Epub 2021 Mar 11.
- Kelly CP. Can we identify patients at high risk of recurrent Clostridium difficile infection? Clin Microbiol Infect. 2012;18(suppl 6):21–27.
- Smits WK, et al. Clostridium difficile infection. Nat Rev Dis Primers. 2016;2:16020. doi: 10.1038/nrdp.2016.20.