SAINT-PREX, Switzerl--(뉴스와이어)--Ferring Pharmaceuticals today announced the presentation at the American College of Gastroenterology (ACG) 2022 Annual Scientific Meeting of seven analyses for RBX2660, an investigational microbiota-based live biotherapeutic studied for its potential to reduce recurrent C. difficile infection (CDI) after antibiotic treatment.

Data was presented from a post hoc subgroup analysis (24-Month Sustained Clinical Response and Safety of RBX2660 in Participants with Recurrent Clostridioides difficile Infection: Subgroup Analysis; Poster number E0100) on the long-term efficacy and safety of RBX2660 in the PUNCH CD open-label Phase 2 trial. Participants in the trial were 18 years of age or older with either two or more episodes of rCDI treated with standard-of-care antibiotics after a primary CDI episode or two or more episodes of severe CDI requiring hospitalization. Treatment success was defined as the absence of CDI diarrhea for eight weeks after completing study treatment. Among the 142 participants treated with RBX2660 (evaluable population), sustained treatment response through six, 12, and 24 months after treatment, respectively, was achieved by 98%, 97.9%, and 93.5% of participants under 65 years of age and by 96.8%, 93.1%, and 88% of participants 65 years of age and older. Similar sustained response rates were observed in participants categorized by sex, race, and number of prior CDI episodes. The analysis also showed that treatment-emergent adverse events (TEAEs) were reported by a similar percentage of participants across demographic subgroups between 6-12 months (range: 31%-43%) and 12-24 months (range: 23%-37%). Most TEAEs were gastrointestinal and mild to moderate in severity.

“C. difficile infection represents a significant public health burden that can cause an unrelenting cycle of recurrence, impacting a person’s long-term health,” said Elizabeth Garner, M.D. M.P.H., Chief Scientific Officer, Ferring Pharmaceuticals, U.S.

Two additional analyses reviewed data from the PUNCH™ CD clinical program and included post hoc analyses suggesting an improvement in health-related quality of life (HRQL) for patients treated with RBX2660. HRQL impact was based on the Clostridioides difficile Health-Related Quality of Life Questionnaire (Cdiff32), a validated disease-specific instrument with three domains (physical, mental, and social), and a total score (all range from 0-100 with 100 being the best possible).

The first analysis (Health-Related Quality of Life in Patients with One Prior Episode of Recurrent Clostridioides difficile Infection: Results from the RBX2660 Phase 3 Randomized, Placebo-Controlled rCDI Trial [PUNCH CD3]; Poster number E0349), was a post hoc analysis of HRQL within an eight-week period for a subgroup of participants in the PUNCH CD3 trial who experienced a first recurrence. The analysis included 66 participants (76.7%) with Cdiff32 data at baseline and at week 8 (43 RBX2660, 23 placebo). Unadjusted analyses showed greater HRQL improvements with RBX2660 versus placebo for total score (13.5±5.7, p<0.05) and mental domain (16.2±6.0, p<0.01), with nonsignificant improvements for physical (11.9±6.1, p=0.07) and social (7.6±7.5, p=0.45) domains. Adjusted analyses showed statistically significant differences (all p<0.05) for total score (11.03, 95% confidence interval: [1.34; 20.72]), physical (10.74, 95% CI: [1.36; 20.13]), and mental (13.07, 95% CI: [2.02; 24.13]) domains.

The second post hoc analysis (Health-Related Quality of Life of Week 8 Responders and Non-Responders: Results from the RBX2660 Phase 3 Randomized, Placebo-Controlled Trial in Recurrent Clostridioides difficile Infection [PUNCH CD3]; Poster number E0348) included responder participants with no recurrence (n=178; 125 RBX2660, 53 placebo) and non-responder participants with C. difficile recurrence (n=7; 3 RBX2660, 4 placebo) in the PUNCH CD3 trial. Among responders, improvements from baseline to week 8 were statistically significant (all p<0.001) for both arms and all Cdiff32 scores. Adjusted analyses among responders found a difference favoring RBX2660 versus placebo at week 8 for the mental domain (7.4, 95% CI: [0.33, 14.43], P<0.05). Among non-responders, numerical improvements in all four scores were observed for RBX2660, while scores remained similar from baseline to week 8 for placebo.

“These two analyses suggest the potential for RBX2660 to help improve the health-related quality of life for patients with recurrent CDI,” said Paul Feuerstadt, M.D., F.A.C.G., A.G.A.F., Yale University School of Medicine.

Additional ACG 2022 Data Presentations

Four additional analyses were presented at ACG 2022, which looked at the efficacy and safety of RBX2660 across different populations, including participants with underlying comorbidities. These analyses included the following:

· An ad hoc analysis of PUNCH CD3-OLS (An Interim Analysis of a Phase 3, Open-Label Study Indicates Efficacy and Safety of RBX2660 in Patients with Recurrent Clostridioides difficile Infection; Session number 56). PUNCH CD3-OLS is an ongoing, open-label phase 3 study evaluating the efficacy and safety of RBX2660. Enrolled participants were 18 years of age or older with medically documented rCDI, including first recurrence patients and broad eligibility criteria. After standard-of-care antibiotics, participants received a single dose of RBX2660. At the time of this analysis, 483 participants had received RBX2660. Treatment success was defined as remaining recurrence-free for 8 weeks after treatment and was achieved by 74.6% of participants whose outcomes could be analyzed (300/402), which is consistent with a 2021 ad hoc analysis. Among the RBX2660 responders (n=300) who completed six months of follow-up (n=262), 84% (220/262) remained CDI recurrence-free. TEAEs were reported by 69% of RBX2660-treated participants. Most TEAEs were mild to moderate in severity and gastrointestinal in nature, with diarrhea and abdominal pain the most commonly reported. This oral presentation received the American College of Gastroenterology’s Outstanding Research Award in Colon Category.

· An ad hoc analysis from PUNCH CD3-OLS (Efficacy and Safety of RBX2660 in Reducing Recurrent Clostridioides difficile Infection in Patients with Underlying Gastrointestinal Comorbidities; Poster number D0099) involving a subgroup of participants from a modified intent-to-treat population (n=402) who had GI comorbidities (gastroesophageal reflux disease, irritable bowel syndrome, diverticulitis, irritable bowel disease, unspecified colitis). Among participants in this subgroup population, treatment success - defined as remaining free of CDI recurrence for eight weeks after treatment - was found among 75% of those treated with RBX2660. Additionally, six month adjudicated results found 84% of RBX2660-treated participants across GI comorbidity subgroups remained CDI recurrence free. A sustained clinical response through six months was maintained in RBX2660 participants with and without GI comorbidities. Overall, adverse events and TEAEs were similar between participants with and without GI comorbidities. Most TEAEs were mild to moderate in severity and GI in nature (predominantly diarrhea and abdominal pain).

· A prespecified post hoc analysis of PUNCH CD3 (Efficacy and Safety of RBX2660 in Patients After First Recurrence of Clostridioides difficile Infection - Results from a Phase 3, Randomized, Placebo-Controlled Study; Poster number D0100), looked at the efficacy and safety of RBX2660 in a subgroup of participants with only one rCDI episode prior to study enrollment (86 of 276), who received a single blinded dose of RBX2660 or placebo. Treatment success, defined as remaining free of CDI recurrence for eight weeks after treatment, was achieved by 79.2% (42/53) of those treated with RBX2660 versus 60.6% (20/33) of those treated with placebo. Participants were monitored for recurrence through six months and the majority of responders remained recurrence free during this time period (RBX2660: 91% [38/42]; placebo: 85% [17/20]). TEAEs were reported by 54.7% (29/53) of RBX2660-treated participants and 33.3% (11/33) of placebo-treated participants, with mild events, mostly gastrointestinal, accounting for the difference.

· A post hoc subgroup analysis of the PUNCH CD3 trial (Efficacy and Safety of RBX2660 in Patients with Recurrent Clostridioides difficile Infection Grouped by Age and Underlying Comorbidities; Poster number D0098), which assessed results from a modified intent-to-treat (mITT) population (n=262) grouped by age and underlying comorbidities using the Charlson Comorbidity Index (CCI) severity scores - mild, moderate, or severe. The CCI is a commonly used index that incorporates 16 conditions and age to estimate the risk of long-term mortality based on comorbidity burden, with severe CCI scores equating to a higher risk of death. Treatment success was defined as remaining CDI recurrence-free eight weeks after treatment. In the total mITT population, 71% of RBX2660-treated participants achieved treatment success compared with 62% of placebo-treated participants. The analysis found a greater percentage of RBX2660-treated participants remained recurrence-free compared to placebo-treated participants in most subgroups: <65: 75% vs. 76% (mild), 70% vs. 45% (moderate), 75% vs. 40% (severe); ages ≥65 to <75 years: 100% vs. 0% (mild), 74% vs. 63% (moderate), 73% vs. 50% (severe); ≥75 years: 50% vs. 100% (moderate), and 64% vs. 63% (severe). In the total safety population (n=267), the overall incidence of TEAEs was 52% for RBX2660-treated participants versus 42% for placebo-treated participants. Across subgroups, most TEAEs were mild or moderate in severity.

About C. difficile infection

C. difficile infection (CDI) is a serious and potentially deadly disease that impacts people across the globe. The C. difficile bacterium causes debilitating symptoms such as severe diarrhea, fever, stomach tenderness or pain, loss of appetite, nausea, and colitis (an inflammation of the colon).[1] Declared a public health threat by the U.S. Centers for Disease Control and Prevention (CDC) requiring urgent and immediate action, CDI causes an estimated half a million illnesses and tens of thousands of deaths in the U.S. alone each year.[1,2,3]

C. difficile infection often is the start of a vicious cycle of recurrence, causing a significant burden for patients and the healthcare system.[4,5] It has been estimated that up to 35% of CDI cases recur after initial diagnosis and people who have had a recurrence are at significantly higher risk of further infections.[6,7,8,9] After the first recurrence, it has been estimated that up to 65% of patients may develop a subsequent recurrence.[8,9]

About RBX2660

RBX2660 is an investigational microbiota-based live biotherapeutic studied for its potential to reduce recurrence of C. difficile infection after antibiotic treatment. RBX2660 has been granted Orphan and Breakthrough Therapy designations from the U.S. Food and Drug Administration (FDA). RBX2660 was developed by Rebiotix, a Ferring company.

About the PUNCH™ CD3 Clinical Trial (Clinicaltrials.gov identifier: NCT03244644)

PUNCH CD3 is a Phase 3, prospective, multi-center, randomized, double-blinded, placebo-controlled clinical trial evaluating the efficacy and safety of RBX2660 vs. placebo in preventing rCDI. The study included adults ages 18 or older who had at least one recurrence after a primary episode of CDI. Participants were followed up to 8 weeks for the efficacy analysis, and up to six months for the safety analysis.

About the PUNCH™ OLS Clinical Trial (Clinicaltrials.gov identifier: NCT02589847)

PUNCH OLS is a Phase 2, prospective, multi-center, open-label study assessing the efficacy of RBX2660 compared to antibiotic-treated historical control. The study included adults ages 18 years or older who had at least two documented recurrent episodes of CDI after a primary episode and completed two rounds of standard oral antibiotic therapy or experienced at least two documented episodes of severe CDI resulting in hospitalization. The primary efficacy endpoint (treatment success) was defined as the absence of C. difficile associated diarrhea without the need for retreatment for CDI and was determined at the eight-week office visit. A secondary outcome was the safety profile of RBX2660 including adverse events and CDI occurrence through 24 months after treatment. A post hoc analysis evaluated RBX2660 responders who remained CDI occurrence free up to 24 months after treatment.

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. Headquartered in Saint-Prex, Switzerland, Ferring is a leader in reproductive medicine and maternal health, and in specialty areas within gastroenterology and urology. Ferring has been developing treatments for mothers and babies for over 50 years and has a portfolio covering treatments from conception to birth. Founded in 1950, privately owned Ferring now employs around 6,000 people worldwide, has its own operating subsidiaries in more than 50 countries, and markets its products in 110 countries.

Learn more at www.ferring.com, or connect with us on Twitter, Facebook, Instagram, LinkedIn and YouTube.

Ferring is committed to exploring the crucial link between the microbiome and human health, beginning with the threat of recurrent C. difficile infection. Ferring is working to develop novel microbiome-based therapeutics to address significant unmet needs and help people live better lives. Connect with us on our dedicated microbiome therapeutics development channels on Twitter and LinkedIn.

References:

[1] Centers for Disease Control and Prevention. What Is C. Diff? 17 Dec. 2018. Available from: https://www.cdc.gov/cdiff/what-is.html

[2] Centers for Disease Control and Prevention. Biggest Threats and Data, 14 Nov. 2019. Available from: https://www.cdc.gov/drugresistance/biggest-threats.html

[3] Fitzpatrick F, Barbut F. Breaking the cycle of recurrent Clostridium difficile. Clin Microbiol Infect. 2012;18(suppl 6):2-4.

[4] Centers for Disease Control and Prevention. 24 June 2020. Available from: https://www.cdc.gov/drugresistance/pdf/threats-report/clostridioides-difficile-508.pdf

[5] Feuerstadt P, et al. J Med Econ. 2020;23(6):603-609.

[6] Riddle DJ, Dubberke ER. Clostridium difficile infection in the intensive care unit. Infect Dis Clin North Am. 2009;23(3):727-743.

[7] 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.

[8] Kelly, CP. Can we identify patients at high risk of recurrent Clostridium difficile infection? Clin Microbiol Infect. 2012;18(suppl 6):21-27.

[9] Smits WK, et al. Clostridium difficile infection. Nat Rev Dis Primers. 2016;2:16020. doi: 10.1038/nrdp.2016.20.

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