DDW ePoster Library

24-WEEK EFFICACY AND SAFETY DATA FROM ECOSPOR-III, A PHASE 3 DOUBLE-BLIND, PLACEBO-CONTROLLED RANDOMIZED TRIAL OF SER-109, AN INVESTIGATIONAL MICROBIOME THERAPEUTIC FOR TREATMENT OF RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION
DDW ePoster Library. Korman L. 05/21/21; 319722; Fr572
Dr. Louis Korman
Dr. Louis Korman
Contributions Biography
Abstract
Engage with the presenter here during ePoster Session: Clostridioides difficile Colitis: Pathogenesis, Diagnosis, Management and Therapy
On Friday, May 21, 2021 12:15 - 1 p.m. EDT

Number: Fr572
24-WEEK EFFICACY AND SAFETY DATA FROM ECOSPOR-III, A PHASE 3 DOUBLE-BLIND, PLACEBO-CONTROLLED RANDOMIZED TRIAL OF SER-109, AN INVESTIGATIONAL MICROBIOME THERAPEUTIC FOR TREATMENT OF RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION

Society: AGA
Track: Microbiome in Gastrointestinal and Liver Diseases
Category: Microbiome & Microbial Therapy

Author(s): Louis Korman5, Bret Lashner2, Colleen Kraft3, Matthew Sims4, Elaine E. Wang1, Kelly Brady1, Christopher B. Ford1, Mary-Jane Lombardo1, Kevin D. Litcofsky1, Jennifer C. Mahoney1, Christopher W. McChalicher1, Jonathan Winkler1, Sarah Garant1, Babara Mcgovern1, Erin McMullen2, Matthew R. Henn1, Michele Trucksis1, Lisa von Moltke11 Seres Therapeutics Inc, Cambridge, Massachusetts, United States; 2 Cleveland Clinic, Cleveland, Ohio, United States; 3 Emory University, Atlanta, Georgia, United States; 4 Beaumont Health, Royal Oak, Michigan, United States; 5 Capital Digestive Care, Washington, DC, District of Columbia, United States

Background:
Antibiotics targeted against C. difficile bacteria are necessary, but insufficient, to achieve a durable clinical response because they have no effect on C. difficile spores that germinate within a disrupted microbiome. In a Phase 3 randomized controlled clinical trial of subjects with recurrent CDI (ECOSPOR III), SER-109, an investigational microbiome therapeutic composed of purified Firmicutes spores, was highly effective with a favorable safety profile, achieving a 73% relative risk reduction in recurrence rates compared to those treated with placebo at week 8 (11.1% vs 41.3%, respectively; p-value <0.001) [Lashner B ACG 2019; LB#1]. Herein, we report the final 24-week efficacy and safety data for SER-109.

Methods:
Adults ≥18 years with rCDI (≥3 episodes in 12 months) were screened at 75 US/CAN sites. CDI was defined as ≥3 unformed stools/day for ≥48 hours with a (+) C. difficile assay. After completion of 10-21 days of vancomycin or fidaxomicin, adults with symptom resolution were randomized 1:1 to SER-109 (4 capsules x 3 days) or matching placebo and stratified by age (≥ or <65 years) and antibiotic received. Primary objectives were safety and efficacy at 8 weeks. Primary efficacy endpoint was rCDI (recurrent toxin+ diarrhea requiring treatment); secondary endpoints included efficacy and safety at 24 weeks after dosing.

Results
287 subjects were screened and 182 randomized (59.9% female; mean age 65.5 years). The most common reason for screen failure was a negative C. difficile toxin assay. A significantly lower proportion of SER-109 subjects had rCDI compared to placebo at week 24 (20.0% vs 49.9%, respectively; RR 0.41; 95% CI 0.26, 0.65; p-value <0.001; Figure 1). SER-109 was well-tolerated with a safety profile similar to placebo. The most common treatment-emergent adverse events (TEAEs) were gastrointestinal and were mainly mild to moderate. No serious TEAEs, infections, deaths or drug discontinuations were deemed related to study drug.

Conclusions
SER-109, an oral live microbiome therapeutic, maintained durable efficacy over 24 weeks after dosing with a safety profile comparable to placebo. By enriching for Firmicute spores, SER-109 achieves high efficacy, while mitigating risk of transmitting infectious agents and represents a major paradigm shift in the clinical management of patients with recurrent CDI. An open-label study for patients with recurrent CDI is currently enrolling
Engage with the presenter here during ePoster Session: Clostridioides difficile Colitis: Pathogenesis, Diagnosis, Management and Therapy
On Friday, May 21, 2021 12:15 - 1 p.m. EDT

Number: Fr572
24-WEEK EFFICACY AND SAFETY DATA FROM ECOSPOR-III, A PHASE 3 DOUBLE-BLIND, PLACEBO-CONTROLLED RANDOMIZED TRIAL OF SER-109, AN INVESTIGATIONAL MICROBIOME THERAPEUTIC FOR TREATMENT OF RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION

Society: AGA
Track: Microbiome in Gastrointestinal and Liver Diseases
Category: Microbiome & Microbial Therapy

Author(s): Louis Korman5, Bret Lashner2, Colleen Kraft3, Matthew Sims4, Elaine E. Wang1, Kelly Brady1, Christopher B. Ford1, Mary-Jane Lombardo1, Kevin D. Litcofsky1, Jennifer C. Mahoney1, Christopher W. McChalicher1, Jonathan Winkler1, Sarah Garant1, Babara Mcgovern1, Erin McMullen2, Matthew R. Henn1, Michele Trucksis1, Lisa von Moltke11 Seres Therapeutics Inc, Cambridge, Massachusetts, United States; 2 Cleveland Clinic, Cleveland, Ohio, United States; 3 Emory University, Atlanta, Georgia, United States; 4 Beaumont Health, Royal Oak, Michigan, United States; 5 Capital Digestive Care, Washington, DC, District of Columbia, United States

Background:
Antibiotics targeted against C. difficile bacteria are necessary, but insufficient, to achieve a durable clinical response because they have no effect on C. difficile spores that germinate within a disrupted microbiome. In a Phase 3 randomized controlled clinical trial of subjects with recurrent CDI (ECOSPOR III), SER-109, an investigational microbiome therapeutic composed of purified Firmicutes spores, was highly effective with a favorable safety profile, achieving a 73% relative risk reduction in recurrence rates compared to those treated with placebo at week 8 (11.1% vs 41.3%, respectively; p-value <0.001) [Lashner B ACG 2019; LB#1]. Herein, we report the final 24-week efficacy and safety data for SER-109.

Methods:
Adults ≥18 years with rCDI (≥3 episodes in 12 months) were screened at 75 US/CAN sites. CDI was defined as ≥3 unformed stools/day for ≥48 hours with a (+) C. difficile assay. After completion of 10-21 days of vancomycin or fidaxomicin, adults with symptom resolution were randomized 1:1 to SER-109 (4 capsules x 3 days) or matching placebo and stratified by age (≥ or <65 years) and antibiotic received. Primary objectives were safety and efficacy at 8 weeks. Primary efficacy endpoint was rCDI (recurrent toxin+ diarrhea requiring treatment); secondary endpoints included efficacy and safety at 24 weeks after dosing.

Results
287 subjects were screened and 182 randomized (59.9% female; mean age 65.5 years). The most common reason for screen failure was a negative C. difficile toxin assay. A significantly lower proportion of SER-109 subjects had rCDI compared to placebo at week 24 (20.0% vs 49.9%, respectively; RR 0.41; 95% CI 0.26, 0.65; p-value <0.001; Figure 1). SER-109 was well-tolerated with a safety profile similar to placebo. The most common treatment-emergent adverse events (TEAEs) were gastrointestinal and were mainly mild to moderate. No serious TEAEs, infections, deaths or drug discontinuations were deemed related to study drug.

Conclusions
SER-109, an oral live microbiome therapeutic, maintained durable efficacy over 24 weeks after dosing with a safety profile comparable to placebo. By enriching for Firmicute spores, SER-109 achieves high efficacy, while mitigating risk of transmitting infectious agents and represents a major paradigm shift in the clinical management of patients with recurrent CDI. An open-label study for patients with recurrent CDI is currently enrolling

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