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.