Intercept Pharmaceuticals Research Project

The Canadian PBC Society would like to inform our members of a new investigational study for participants with Primary Biliary Cirrhosis ( PBC ) .  Intercept Pharmaceuticals is sponsoring this study; over 20 centers in the US and Canada are participating.  (Sites in Canada are expected to open by July 2012.)  They are looking for PBC patients with elevated alkaline phosphatase levels and who have been taking UDCA (URSO) for at least 12 months OR are unable to tolerate UDCA (and stopped taking it at least three months before entry into the study).  A website with information about the clinical study and study locations can be found at  The website also contains good general information about participating in clinical trials with a section on frequently asked questions.  If you are interested in learning more about this PBC study, or have a friend or relative who may be interested, please check it out.  Other sources for information include the sponsor’s website or the U.S. National Institutes of Health.
Note: The notice posted above is for information purposes only. If you are interested in participation please consult your own health care provider.

Intercept Announces Positive Pivotal Phase 3 POISE Trial Results

NEW YORK, March 16, 2014 — We have just received positive results for the POISE Phase III study of obeticholic acid (OCA) as a second line treatment in patients with primary biliary cirrhosis. The study showed that patients who received OCA in combination with ursodeoxycholic acid (UDCA) experienced a clinically meaningful improvement in serum alkaline phosphatase counts (ALP) and other measures of liver function, which can significantly lower the risk of progressing to liver failure. These results, along with the positive data from Intercept's Phase II studies of OCA in PBC, provide further evidence that this treatment has the potential to result in important clinical benefit to PBC patients. Below is a link to our press release that went out yesterday, which provides an overview of the topline study results that are available at this time; we anticipate that more detailed results from the study will be presented at the upcoming International Liver Congress in London this April.

More information

Breaking news from Toronto Western Hospital Liver Centre

In close collaboration with genetics experts at Mount Sinai Hospital, also in Toronto, as well as collaborators across Canada and the US, they have now published one of the most important breakthroughs in PBC research for at least a decade, if not longer. This work was in particular supported by the Canadian PBC Society from the outset, as well as by a major grant from the Canadian Institute for Health Research.

Writing in the highly influential New England Journal of Medicine, Dr Hirschfield and his colleagues outline new genes that are associated with the development of PBC. These genes play an important role in how the immune system works and it is now clear that subtle changes in their function may be related to why patients develop this chronic disease. Commenting on the work, Gideon Hirschfield who runs the Autoimmune liver disease service in Toronto, said "We're really excited by these findings. For the first time ever we are closer to understanding why PBC begins, and how we might treat it better. We're very grateful to all the patients from across Canada and America who have given DNA samples and to the PBC society who were pivotal in providing resources to collect the Canadian samples. We're delighted that a Canadian led team is the first in the world to do this pivotal study, and hope this ushers in an era of even more collaboration as we try and work with DNA samples from many thousands of patients in the future to tease apart this enigmatic disease." Jenny Heathcote and Kathy Siminovitch initiated the study about 5 years ago. Jenny, well known to patients across the world as a leading authority in PBC said "These results point to why PBC develops and where new drugs should be targeted. I'm thrilled that the patients and doctors have worked so closely together to make this breakthrough, and that a pan-Canadian network of liver centres has so successfully collaborated. This is just the start and we hope that our autoimmune liver disease clinic at the Toronto Western, as well as those across Canada, continue to be supported by patients and clinicians".

The paper entitled "Primary Biliary Cirrhosis Associated with HLA, IL12A, and IL12RB2 Variants" was published on-line at the New England Journal of Medicine on May 20th 2009.

For further information on PBC please contact Catalina Coltescu at or visit the Toronto Western Hospital Liver Centre website at Recruitment continues at full pace for this study, as there is still a lot more good work to do!

To view the article at the New England Journal of Medicine visit this page

Mount Sinai Hospital researcher gives new hope for patients with liver disease

In a study published by the New England Journal of Medicine online on May 20, 2009, (and in the June 11, 2009 print issue) Mount Sinai Hospital's Dr. Katherine Siminovitch has discovered a new genetic pathway (a gene "road map") that could provide personalized treatment options for patients with a devastating liver disease. The study offers great hope in treating other autoimmune diseases such as rheumatoid arthritis.

"This finding provides the very first clues into the causes of primary biliary cirrhosis and gives us new ideas for treating this and many other autoimmune diseases that affect so many Canadians," said Dr. Siminovitch, Senior Investigator and Sherman Family Research Chair in Genomic Medicine at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Director of the Fred A. Litwin & Family Centre in Genetic Medicine, and Director of Genomic Medicine at the University Health Network. "We are accelerating our ability to diagnose disease, apply leading-edge technology to discovery of the disease-causing genes and translate our findings into improved, personalized treatment. These advances give us hope for improving outcomes for affected patients in the very near future."

Dr. Siminovitch and colleagues identified three genes in one pathway that are involved in susceptibility to primary biliary cirrhosis (PBC), an autoimmune disease that destroys the bile ducts in the liver. Until now, the cause of PBC has remained unknown and there is only one available treatment for this potentially fatal disease. Patients who do not respond to medical treatment may require liver transplantation. PBC usually strikes women between the ages of 40-60 years, and affects about one in 1,000 women over the age of 40 years.

The researchers studied 600 patients with PBC in Canada and 400 patients in the United States through a partnership with the Mayo Clinic, along with 1,000 controls (patients without the disease). Patients with PBC often have other autoimmune diseases as well, suggesting that these diseases may be caused by some of the same genetic factors as PBC.

"We can now pinpoint any gene for any disease," said Dr. Jim Woodgett, Director of Research, Samuel Lunenfeld Research Institute of Mount Sinai Hospital. "Dr. Siminovitch's work is an excellent example of how genetic findings are making a difference in patients' lives."

The study was funded by Canadian Institutes of Health Research and the Ontario Research Fund. Additional support was provided by the Canadian PBC Society.

About the Samuel Lunenfeld Research Institute of Mount Sinai Hospital

The Samuel Lunenfeld Research Institute of Mount Sinai Hospital, a University of Toronto affiliated research centre established in 1985, is one of the world's premier centres in biomedical research. Thirty-four principal investigators lead research in diabetes, cancer biology, epidemiology, stem cell research, women's and infants' health, neurobiology and systems biology. For more information on the Samuel Lunenfeld Research Institute, please visit

The original press release may be viewed here.


Primary Biliary Cirrhosis (PBC) is a chronic, but variably progressive chronic liver disease caused by ongoing inflammation of the small bile ducts within the liver. The result is cholestasis (failure of bile flow), which causes damage to the cells of the liver and promotes scarring of the liver, and this may lead to cirrhosis (nodular liver with loss of normal architecture).

The disease generally affects middle-aged women (40-60 years), but it has been described in a 15 year old. It may affect males too. For every 9 women with PBC there is one man affected.

PBC is a presumed autoimmune disease the cause of which is unknown. Genetic predisposition appears to play an important role in its pathogenesis (cause).

Our PBC group at the Liver Clinic, Toronto Western Hospital has had a long-standing interest in the pathogenesis, epidemiology, therapy and, more recently, genetics in PBC. Throughout the years we have conducted many national and international collaborative studies.

In February 2005 the Canadian Institutes of Health Research (CIHR) approved our application entitled “Family studies in PBC”. The study will be funded for 3 years.

The goal of our research study is to identify susceptibility genes for PBC by testing DNA in samples of blood and correlating the results with clinical information on both patients with PBC as well as unaffected and affected parents and siblings. We will study these individuals and a cohort of healthy controls (spouses and friends will also be asked to act as the local “control” population) with genetic markers to screen for a select set of candidate genes as well as the full genome for variants associated with PBC. There are three sites currently involved in this study: Toronto, London and Halifax that follow over 600 patients.

We will recruit patients with PBC (primarily from Ontario and Nova Scotia) and ~ 1800 of their first-degree relatives. Detailed clinical and demographic data will be obtained on all study participants and blood for DNA analysis and storage of a mononuclear cell preparation will be collected. All data will be stored in an Oracle-based relational database. Patient recruitment will involve obtaining written informed consent. Once received, documentation of the clinical (including demographic), serologic and histologic data on all patients as well as collection of blood samples for DNA analysis will be obtained. All study patients will be initially approached by their physician with follow up by the study coordinator and, if willing to participate, these individuals and their first degree relatives will be asked to provide contact addresses. They will be mailed explanatory consent forms and, once these have been returned signed, patients and their first-degree relatives will be sent questionnaires to complete and be asked to provide a blood sample (either at the study site, local hospital or private laboratory). The Canadian PBC Society will facilitate the correspondence with some patients via e-mail to minimize our mailing costs.

The blood collection for this 3-year study will cost approx $105,000. The Canadian PBC Society is pleased to announce that they raised these funds and finalised their commitment to covering this cost (which CIHR rarely covers). Their enthusiasm, effort and commitment to raise and donate the money to cover the entire amount are really much appreciated.

We hope that the study will provide opportunities for predicting disease risk, prognosis and drug responsiveness and will also provide the framework for elucidating molecular targets for use in therapeutic intervention.


 Last modified May 5, 2012