87 percent of patients with recurrent C. difficile infection met primary endpoint; 97 percent achieved clinical cure
CAMBRIDGE, MA, USA I February 9, 2016 I Seres Therapeutics, Inc. (NASDAQ:MCRB), a leading microbiome therapeutics company, announced that positive results from the Phase 1b/2 study of SER-109 in recurrent Clostridium difficile infection (CDI) were published today in The Journal of Infectious Diseases.
The study evaluated the efficacy and safety of SER-109 for recurrent CDI, and measured corresponding alterations in the gut microbiota. Results demonstrated that 87 percent of patients (26 of 30) met the predefined endpoint of preventing recurrent CDI within eight weeks following administration of SER-109. Most importantly, 97 percent of patients (29 of 30) achieved clinical cure during the eight-week period after SER-109 dosing, as defined by the absence of CDI requiring antibiotic treatment. By contrast, the expected cure rates in people treated with the standard of care, i.e. antibiotics, for recurrent CDI range from 23-31 percent, according to a recent well-controlled study.1
“The impressive level of efficacy observed with SER-109 treatment is striking when compared with the high rate of recurrence expected in this population,” said Dr. Stuart H. Cohen, MD, Chief, Division of Infectious Diseases, University of California, Davis. “These results demonstrate the potential of SER-109 to effectively treat recurrent CDI. With current treatment approaches having significant limitations, SER-109 has the potential to fundamentally change the management of this urgent health issue.”
SER-109 induced clinical cures occurred in parallel with a rapid and sustained remodeling of the gut microbiome, supporting the treatment premise, i.e. mechanism of action, that addressing the underlying dysbiosis (unhealthy microbiome) that gives rise to CDI will produce a profound clinical benefit.
“This study showed that we can address the root cause of C. difficile infection by inducing a healthy and diverse microbiome,” said Roger Pomerantz, MD, President, Chief Executive Officer and Chairman of Seres. “We are now building on these important results by advancing our ongoing SER-109 Phase 2 study in recurrent CDI and by developing SER-262, a synthetically derived product candidate, for patients with primary CDI. The microbiome represents a critically important new modality to address CDI and multiple other clinical indications, and we are proud to be leading the way. Our goal is for all patients with CDI, whether primary or recurrent, to be treated with a Seres microbiome drug to stop recurrence in this expanding epidemic in the United States and around the world.”
Study Details
The Phase 1b/2 open-label, single arm, descending-dose study enrolled 30 patients with recurrent CDI at four leading medical centers in the United States: Massachusetts General Hospital in Boston, Mass.; Mayo Clinic in Rochester, Minn.; Miriam Hospital in Providence, R.I., and Emory University Hospital in Atlanta, Ga. All enrolled patients received standard-of-care antibiotic treatment, followed by oral administration of SER-109.
Of the 30 study patients, 26 (87%) achieved the primary endpoint of absence of diarrhea with a positive C. difficile test up to eight weeks following dosing. Three of the four patients who did not meet the primary endpoint were determined by their primary investigator to be recovering from CDI, and all symptoms resolved without further therapeutic intervention or antibiotics. In total, 29 of 30 patients (97%) achieved full clinical cure of recurrent CDI following SER-109 administration.
SER-109 was well tolerated in the study, with the most common adverse events being mild to moderate gastrointestinal symptoms. No drug related serious adverse events were observed.
In a corresponding finding, microbial diversity increased significantly at eight weeks, driven by engraftment of SER-109 related microbiota, as well as the augmentation of key bacterial species following administration. The reduction or elimination of pathobionts, species that colonize the gut and can cause infection in susceptible individuals, was observed in a majority of patients. These changes were detected as early as day four and were durable through 24 weeks of observation, with subjects’ microbiomes returning to a state reflective of healthy individuals.
About SER-109
SER-109, an oral capsule, is Seres’ lead Ecobiotic® microbiome therapeutic in clinical testing for the treatment of recurrent Clostridium difficile infection (CDI). SER-109 was developed utilizing the Seres Microbiome Therapeutics™ platform that provides deep insight into the ecologies of disease and then identifies microbial compositions that can catalyze a shift to a healthier state.
About Clostridium difficile infection
Clostridium difficile infection (CDI) is one of the top three most urgent antibiotic-resistant bacterial threats in the U.S., according to the Centers for Disease Control. CDI is a rapidly growing problem associated with antibiotic use. It is a leading cause of hospital acquired infection in the U.S. and is responsible for the death of approximately 29,000 Americans each year. The incidence of first occurrence is between approximately 640,000 and 820,000 patients per year in the U.S., and approximately 85,000 to 110,000 CDI patients in the U.S. have more than one recurrence each year.
About Seres Therapeutics
Seres Therapeutics, Inc. is a leading microbiome therapeutics platform company developing a novel class of biological drugs that are designed to treat disease by restoring the function of a dysbiotic microbiome characterized by an increased presence of pathogenic bacterial species, where the natural state of bacterial diversity is imbalanced. Seres’ most advanced program, SER-109, has successfully completed a Phase 1b/2 study demonstrating a clinical benefit in patients with recurring Clostridium difficile infection (CDI) and is currently being evaluated in a Phase 2 study in recurring CDI. The FDA has granted SER-109 Orphan Drug, as well as Breakthrough Therapy, designations. Seres’ second clinical candidate, SER-287, is being evaluated in a Phase 1b study in patients with mild-to-moderate ulcerative colitis.
1. van Nood et al., New England Journal of Medicine, 2013.
SOURCE: Seres Therapeutics
Post Views: 92
87 percent of patients with recurrent C. difficile infection met primary endpoint; 97 percent achieved clinical cure
CAMBRIDGE, MA, USA I February 9, 2016 I Seres Therapeutics, Inc. (NASDAQ:MCRB), a leading microbiome therapeutics company, announced that positive results from the Phase 1b/2 study of SER-109 in recurrent Clostridium difficile infection (CDI) were published today in The Journal of Infectious Diseases.
The study evaluated the efficacy and safety of SER-109 for recurrent CDI, and measured corresponding alterations in the gut microbiota. Results demonstrated that 87 percent of patients (26 of 30) met the predefined endpoint of preventing recurrent CDI within eight weeks following administration of SER-109. Most importantly, 97 percent of patients (29 of 30) achieved clinical cure during the eight-week period after SER-109 dosing, as defined by the absence of CDI requiring antibiotic treatment. By contrast, the expected cure rates in people treated with the standard of care, i.e. antibiotics, for recurrent CDI range from 23-31 percent, according to a recent well-controlled study.1
“The impressive level of efficacy observed with SER-109 treatment is striking when compared with the high rate of recurrence expected in this population,” said Dr. Stuart H. Cohen, MD, Chief, Division of Infectious Diseases, University of California, Davis. “These results demonstrate the potential of SER-109 to effectively treat recurrent CDI. With current treatment approaches having significant limitations, SER-109 has the potential to fundamentally change the management of this urgent health issue.”
SER-109 induced clinical cures occurred in parallel with a rapid and sustained remodeling of the gut microbiome, supporting the treatment premise, i.e. mechanism of action, that addressing the underlying dysbiosis (unhealthy microbiome) that gives rise to CDI will produce a profound clinical benefit.
“This study showed that we can address the root cause of C. difficile infection by inducing a healthy and diverse microbiome,” said Roger Pomerantz, MD, President, Chief Executive Officer and Chairman of Seres. “We are now building on these important results by advancing our ongoing SER-109 Phase 2 study in recurrent CDI and by developing SER-262, a synthetically derived product candidate, for patients with primary CDI. The microbiome represents a critically important new modality to address CDI and multiple other clinical indications, and we are proud to be leading the way. Our goal is for all patients with CDI, whether primary or recurrent, to be treated with a Seres microbiome drug to stop recurrence in this expanding epidemic in the United States and around the world.”
Study Details
The Phase 1b/2 open-label, single arm, descending-dose study enrolled 30 patients with recurrent CDI at four leading medical centers in the United States: Massachusetts General Hospital in Boston, Mass.; Mayo Clinic in Rochester, Minn.; Miriam Hospital in Providence, R.I., and Emory University Hospital in Atlanta, Ga. All enrolled patients received standard-of-care antibiotic treatment, followed by oral administration of SER-109.
Of the 30 study patients, 26 (87%) achieved the primary endpoint of absence of diarrhea with a positive C. difficile test up to eight weeks following dosing. Three of the four patients who did not meet the primary endpoint were determined by their primary investigator to be recovering from CDI, and all symptoms resolved without further therapeutic intervention or antibiotics. In total, 29 of 30 patients (97%) achieved full clinical cure of recurrent CDI following SER-109 administration.
SER-109 was well tolerated in the study, with the most common adverse events being mild to moderate gastrointestinal symptoms. No drug related serious adverse events were observed.
In a corresponding finding, microbial diversity increased significantly at eight weeks, driven by engraftment of SER-109 related microbiota, as well as the augmentation of key bacterial species following administration. The reduction or elimination of pathobionts, species that colonize the gut and can cause infection in susceptible individuals, was observed in a majority of patients. These changes were detected as early as day four and were durable through 24 weeks of observation, with subjects’ microbiomes returning to a state reflective of healthy individuals.
About SER-109
SER-109, an oral capsule, is Seres’ lead Ecobiotic® microbiome therapeutic in clinical testing for the treatment of recurrent Clostridium difficile infection (CDI). SER-109 was developed utilizing the Seres Microbiome Therapeutics™ platform that provides deep insight into the ecologies of disease and then identifies microbial compositions that can catalyze a shift to a healthier state.
About Clostridium difficile infection
Clostridium difficile infection (CDI) is one of the top three most urgent antibiotic-resistant bacterial threats in the U.S., according to the Centers for Disease Control. CDI is a rapidly growing problem associated with antibiotic use. It is a leading cause of hospital acquired infection in the U.S. and is responsible for the death of approximately 29,000 Americans each year. The incidence of first occurrence is between approximately 640,000 and 820,000 patients per year in the U.S., and approximately 85,000 to 110,000 CDI patients in the U.S. have more than one recurrence each year.
About Seres Therapeutics
Seres Therapeutics, Inc. is a leading microbiome therapeutics platform company developing a novel class of biological drugs that are designed to treat disease by restoring the function of a dysbiotic microbiome characterized by an increased presence of pathogenic bacterial species, where the natural state of bacterial diversity is imbalanced. Seres’ most advanced program, SER-109, has successfully completed a Phase 1b/2 study demonstrating a clinical benefit in patients with recurring Clostridium difficile infection (CDI) and is currently being evaluated in a Phase 2 study in recurring CDI. The FDA has granted SER-109 Orphan Drug, as well as Breakthrough Therapy, designations. Seres’ second clinical candidate, SER-287, is being evaluated in a Phase 1b study in patients with mild-to-moderate ulcerative colitis.
1. van Nood et al., New England Journal of Medicine, 2013.
SOURCE: Seres Therapeutics
Post Views: 92
