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WASHINGTON – A rationally designed microbiome-based pill successfully eradicated recurrent Clostridium difficile infection in 29 of 30 patients in an early study presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
Preliminary data were presented at the 2014 James W. Freston Conference sponsored by the American Gastroenterological Association in August.
The patients in the phase I/II study were divided into two separate 15-patient cohorts and were given two different dose levels of the therapy, SER-109. The drug contains spores from gram-positive bacteria that are taken from stool and then purified to kill the vegetative bacteria, said David Cook, Ph.D., executive vice president and chief scientific officer of Cambridge, Mass.–based Seres Health.
The therapy appears to work by restoring the gut flora to a normal balance after having been disrupted by antibiotic treatment.
It is not the first attempt to encapsulate a fecal transplant; Dr. Thomas Louie of the University of Calgary (Alberta), presented data on his very effective formulation against C. difficile at the ID Week annual meeting in 2013.
In the current study, the first cohort received a mean dose of 1.5 × 109 spores and the second cohort received a dose of 1 × 108 spores. In the early studies, the number of pills given to achieve that dose varied. The aim is to contain the dose in a few tablets for a commercial product, Dr. Cook said.
All doses were given on 1 or 2 days at the study’s start; there was no need for additional doses.
Patients were as young as 22 years old and as old as 88 years, and all had three or more laboratory-confirmed C. difficile infections over the previous year. They had to have a life expectancy of 3 months or longer and be able to give informed consent. They were excluded if they had any immunosuppression, a history of irritable bowel disease, total colectomy, cirrhosis, a need for antibiotics within 6 weeks of baseline, prior fecal transplant, or if they were in intensive care. There were 10 women and five men in each cohort.
After patients stopped taking antibiotics, there was a washout period after which they took SER-109. Stool was collected on day four and at 1, 2, 4, 8, and 24 weeks. Efficacy was assessed at the 8-week time point.
In the first group, 13 of the 15 patients achieved the protocol-defined endpoint: absence of C. difficile over the 8 weeks.
The two patients who failed had self-limited, transient diarrhea with a positive C. difficile test, but neither required antibiotics and both recovered within 24 hours, so they were considered to not have recurrent C. difficile, said Dr. Cook. In the second cohort, 14 of the 15 patients were free of C. difficile at 8 weeks. The patient who failed had diarrhea and a positive C. difficile test, and the diarrhea did not resolve on its own. She required antibiotics to achieve remission.
There were no serious adverse events in the study.
The company hopes to eventually conduct a phase III study and seek Food and Drug Administration approval, but it is too early to say when that might occur, said Dr. Cook.
On Twitter @aliciaault
This story was updated on October 14.
The AGA hosted the annual James W. Freston conference in Chicago this August, and this year's topic was therapeutic innovations in microbiome research and technology, with a focus on fecal microbiota transplantation (FMT). There were more than 140 participants from 16 countries present to discuss evolving research and clinical approaches to FMT.
The 2-day meeting opened with lectures highlighting evolving knowledge about the human microbiome, and how quickly its composition can change with environmental exposures such as travel or diet. These were followed by additional presentations about FMT as a treatment for Clostridium difficile and inflammatory bowel disease, and intriguing work on the role of the gut microbiome in the metabolic syndrome. There were many productive discussions among the FMT enthusiasts, some of which are summarized in this issue of GI & Hepatology News. The final session of the meeting featured presentations about institutional review board regulation of trials involving FMT, and updates from the Food and Drug Administration.
It is clear that FMT is an effective treatment for recurrent C. diff., and may even be positioned as an earlier treatment option for some patients. The short-term safety of FMT in existing trials is reassuring, but there was general consensus at the meeting that we need further study of long-term outcomes of recipients. In the United States, the FDA has relaxed its stance on FMT for recurrent C. diff., but an investigational new drug application must be filed with the FDA for its use for any other purposes. Studies of FMT for inflammatory bowel diseases, irritable bowel syndrome, and other conditions are quite limited at this time, and it is clear that additional research is needed before we will understand the associations and potential causality related to the microbiome. In addition, there is a desperate need for further understanding of the complex ecology of the gut microbiome as well as what additional viruses, phages, and proteins may be transferred from a donor to recipient.
Patients have eagerly embraced FMT as a potential treatment for a variety of illnesses, but the evidence for safety and efficacy for any conditions beyond C. diff. is lacking. Therefore, many attendees at the conference emphasized the need for better education about the potential risks and the need for more study.
The Freston conference was a great success, and highlighted some of the important progress that has been made in understanding the human microbiome and its therapeutic potential, but also underscored the near-term research priorities and safety concerns.
Dr. David T. Rubin is Joseph B. Kirsner Professor of Medicine, section chief of gastroenterology, hepatology and nutrition, and codirector of the Digestive Diseases Center, University of Chicago. He was co-course director of the Freston conference with Dr. Stacy Kahn.
The AGA hosted the annual James W. Freston conference in Chicago this August, and this year's topic was therapeutic innovations in microbiome research and technology, with a focus on fecal microbiota transplantation (FMT). There were more than 140 participants from 16 countries present to discuss evolving research and clinical approaches to FMT.
The 2-day meeting opened with lectures highlighting evolving knowledge about the human microbiome, and how quickly its composition can change with environmental exposures such as travel or diet. These were followed by additional presentations about FMT as a treatment for Clostridium difficile and inflammatory bowel disease, and intriguing work on the role of the gut microbiome in the metabolic syndrome. There were many productive discussions among the FMT enthusiasts, some of which are summarized in this issue of GI & Hepatology News. The final session of the meeting featured presentations about institutional review board regulation of trials involving FMT, and updates from the Food and Drug Administration.
It is clear that FMT is an effective treatment for recurrent C. diff., and may even be positioned as an earlier treatment option for some patients. The short-term safety of FMT in existing trials is reassuring, but there was general consensus at the meeting that we need further study of long-term outcomes of recipients. In the United States, the FDA has relaxed its stance on FMT for recurrent C. diff., but an investigational new drug application must be filed with the FDA for its use for any other purposes. Studies of FMT for inflammatory bowel diseases, irritable bowel syndrome, and other conditions are quite limited at this time, and it is clear that additional research is needed before we will understand the associations and potential causality related to the microbiome. In addition, there is a desperate need for further understanding of the complex ecology of the gut microbiome as well as what additional viruses, phages, and proteins may be transferred from a donor to recipient.
Patients have eagerly embraced FMT as a potential treatment for a variety of illnesses, but the evidence for safety and efficacy for any conditions beyond C. diff. is lacking. Therefore, many attendees at the conference emphasized the need for better education about the potential risks and the need for more study.
The Freston conference was a great success, and highlighted some of the important progress that has been made in understanding the human microbiome and its therapeutic potential, but also underscored the near-term research priorities and safety concerns.
Dr. David T. Rubin is Joseph B. Kirsner Professor of Medicine, section chief of gastroenterology, hepatology and nutrition, and codirector of the Digestive Diseases Center, University of Chicago. He was co-course director of the Freston conference with Dr. Stacy Kahn.
The AGA hosted the annual James W. Freston conference in Chicago this August, and this year's topic was therapeutic innovations in microbiome research and technology, with a focus on fecal microbiota transplantation (FMT). There were more than 140 participants from 16 countries present to discuss evolving research and clinical approaches to FMT.
The 2-day meeting opened with lectures highlighting evolving knowledge about the human microbiome, and how quickly its composition can change with environmental exposures such as travel or diet. These were followed by additional presentations about FMT as a treatment for Clostridium difficile and inflammatory bowel disease, and intriguing work on the role of the gut microbiome in the metabolic syndrome. There were many productive discussions among the FMT enthusiasts, some of which are summarized in this issue of GI & Hepatology News. The final session of the meeting featured presentations about institutional review board regulation of trials involving FMT, and updates from the Food and Drug Administration.
It is clear that FMT is an effective treatment for recurrent C. diff., and may even be positioned as an earlier treatment option for some patients. The short-term safety of FMT in existing trials is reassuring, but there was general consensus at the meeting that we need further study of long-term outcomes of recipients. In the United States, the FDA has relaxed its stance on FMT for recurrent C. diff., but an investigational new drug application must be filed with the FDA for its use for any other purposes. Studies of FMT for inflammatory bowel diseases, irritable bowel syndrome, and other conditions are quite limited at this time, and it is clear that additional research is needed before we will understand the associations and potential causality related to the microbiome. In addition, there is a desperate need for further understanding of the complex ecology of the gut microbiome as well as what additional viruses, phages, and proteins may be transferred from a donor to recipient.
Patients have eagerly embraced FMT as a potential treatment for a variety of illnesses, but the evidence for safety and efficacy for any conditions beyond C. diff. is lacking. Therefore, many attendees at the conference emphasized the need for better education about the potential risks and the need for more study.
The Freston conference was a great success, and highlighted some of the important progress that has been made in understanding the human microbiome and its therapeutic potential, but also underscored the near-term research priorities and safety concerns.
Dr. David T. Rubin is Joseph B. Kirsner Professor of Medicine, section chief of gastroenterology, hepatology and nutrition, and codirector of the Digestive Diseases Center, University of Chicago. He was co-course director of the Freston conference with Dr. Stacy Kahn.
WASHINGTON – A rationally designed microbiome-based pill successfully eradicated recurrent Clostridium difficile infection in 29 of 30 patients in an early study presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
Preliminary data were presented at the 2014 James W. Freston Conference sponsored by the American Gastroenterological Association in August.
The patients in the phase I/II study were divided into two separate 15-patient cohorts and were given two different dose levels of the therapy, SER-109. The drug contains spores from gram-positive bacteria that are taken from stool and then purified to kill the vegetative bacteria, said David Cook, Ph.D., executive vice president and chief scientific officer of Cambridge, Mass.–based Seres Health.
The therapy appears to work by restoring the gut flora to a normal balance after having been disrupted by antibiotic treatment.
It is not the first attempt to encapsulate a fecal transplant; Dr. Thomas Louie of the University of Calgary (Alberta), presented data on his very effective formulation against C. difficile at the ID Week annual meeting in 2013.
In the current study, the first cohort received a mean dose of 1.5 × 109 spores and the second cohort received a dose of 1 × 108 spores. In the early studies, the number of pills given to achieve that dose varied. The aim is to contain the dose in a few tablets for a commercial product, Dr. Cook said.
All doses were given on 1 or 2 days at the study’s start; there was no need for additional doses.
Patients were as young as 22 years old and as old as 88 years, and all had three or more laboratory-confirmed C. difficile infections over the previous year. They had to have a life expectancy of 3 months or longer and be able to give informed consent. They were excluded if they had any immunosuppression, a history of irritable bowel disease, total colectomy, cirrhosis, a need for antibiotics within 6 weeks of baseline, prior fecal transplant, or if they were in intensive care. There were 10 women and five men in each cohort.
After patients stopped taking antibiotics, there was a washout period after which they took SER-109. Stool was collected on day four and at 1, 2, 4, 8, and 24 weeks. Efficacy was assessed at the 8-week time point.
In the first group, 13 of the 15 patients achieved the protocol-defined endpoint: absence of C. difficile over the 8 weeks.
The two patients who failed had self-limited, transient diarrhea with a positive C. difficile test, but neither required antibiotics and both recovered within 24 hours, so they were considered to not have recurrent C. difficile, said Dr. Cook. In the second cohort, 14 of the 15 patients were free of C. difficile at 8 weeks. The patient who failed had diarrhea and a positive C. difficile test, and the diarrhea did not resolve on its own. She required antibiotics to achieve remission.
There were no serious adverse events in the study.
The company hopes to eventually conduct a phase III study and seek Food and Drug Administration approval, but it is too early to say when that might occur, said Dr. Cook.
On Twitter @aliciaault
This story was updated on October 14.
WASHINGTON – A rationally designed microbiome-based pill successfully eradicated recurrent Clostridium difficile infection in 29 of 30 patients in an early study presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
Preliminary data were presented at the 2014 James W. Freston Conference sponsored by the American Gastroenterological Association in August.
The patients in the phase I/II study were divided into two separate 15-patient cohorts and were given two different dose levels of the therapy, SER-109. The drug contains spores from gram-positive bacteria that are taken from stool and then purified to kill the vegetative bacteria, said David Cook, Ph.D., executive vice president and chief scientific officer of Cambridge, Mass.–based Seres Health.
The therapy appears to work by restoring the gut flora to a normal balance after having been disrupted by antibiotic treatment.
It is not the first attempt to encapsulate a fecal transplant; Dr. Thomas Louie of the University of Calgary (Alberta), presented data on his very effective formulation against C. difficile at the ID Week annual meeting in 2013.
In the current study, the first cohort received a mean dose of 1.5 × 109 spores and the second cohort received a dose of 1 × 108 spores. In the early studies, the number of pills given to achieve that dose varied. The aim is to contain the dose in a few tablets for a commercial product, Dr. Cook said.
All doses were given on 1 or 2 days at the study’s start; there was no need for additional doses.
Patients were as young as 22 years old and as old as 88 years, and all had three or more laboratory-confirmed C. difficile infections over the previous year. They had to have a life expectancy of 3 months or longer and be able to give informed consent. They were excluded if they had any immunosuppression, a history of irritable bowel disease, total colectomy, cirrhosis, a need for antibiotics within 6 weeks of baseline, prior fecal transplant, or if they were in intensive care. There were 10 women and five men in each cohort.
After patients stopped taking antibiotics, there was a washout period after which they took SER-109. Stool was collected on day four and at 1, 2, 4, 8, and 24 weeks. Efficacy was assessed at the 8-week time point.
In the first group, 13 of the 15 patients achieved the protocol-defined endpoint: absence of C. difficile over the 8 weeks.
The two patients who failed had self-limited, transient diarrhea with a positive C. difficile test, but neither required antibiotics and both recovered within 24 hours, so they were considered to not have recurrent C. difficile, said Dr. Cook. In the second cohort, 14 of the 15 patients were free of C. difficile at 8 weeks. The patient who failed had diarrhea and a positive C. difficile test, and the diarrhea did not resolve on its own. She required antibiotics to achieve remission.
There were no serious adverse events in the study.
The company hopes to eventually conduct a phase III study and seek Food and Drug Administration approval, but it is too early to say when that might occur, said Dr. Cook.
On Twitter @aliciaault
This story was updated on October 14.
AT ICAAC 2014
Key clinical point: A new oral medication might eventually replace fecal transplants.
Major finding: Recurrent Clostridium difficile infection was eradicated in 29 of 30 patients.
Data source: Open-label prospective study that assessed absence of C. difficile at 8 weeks post therapy.
Disclosures: The study was sponsored by Seres Health. Dr. Cook is a Seres employee.
