The International Liver Congress is a highlight of the year for liver physicians and patients. It is one of two international conferences where people meet and discuss new ways of looking after liver disease. The conference is thematic as well as general in principal. This year we have summarized the PBC-related research presented at the International Liver Congress 2019, EASL in Vienna, Austria for you.
Dr. Pietro Invenizzi presented preliminary results from a phase 2 (early stage of development) clinical trial on a possible future treatment for PBC, GKT831. At this time, 92 patients have completed 6 weeks of treatment and a reduction in biochemical markers of cholestasis was observed. The treatment appeared to be well tolerated with no signs of itch or fatigue. The novel thing about GKT831 is that it is focused on targeting liver scarring, which differs to some other drugs for PBC that are more focused on bile duct injury.
Summary slide from presentation by Dr. Pietro Invenizzi on GKT831.
Dr. Velimir Luketic presented results from a trial of two doses of elafibranor, another potential future treatment for PBC. This study reported that both doses of elafibranor reduced blood markers of cholestatis and improved lipid health. Elafibranor was well tolerated and was not associated with itch. This drug is moving towards a phase 3 trial (the stage just before it might be launched for sale). The way this drug works is similar to drugs like Seladelpar (already a late stage trial in Canada recruiting now) and Bezafibrate (a drug sometimes given ‘off-label’ because it is not approved for patients with PBC).
Dr. Gideon Hirschfield presenting a summary of potential treatments for PBC in the future
Further insight into current treatments for PBC
Dr. Christophe Corpechot presented results showing that continued treatment with UDCA after liver transplantation lowers the chance of PBC recurrence and rejection of the new liver. This is interesting and mirrors what most Canadian patients get, which is now a continuation of UDCA after a liver transplant.
Lena Smets presented results showing that treatment with bezafibrate improved the effect of treatment with obeticholic acid in 16 patients. This combination of treatments showed positive effects on blood markers of cholestasis. In patients treated with obeticholic acid who reported itching, the introduction of bezafibrate decreased itch in more than 60% of patients. The combination of therapies was well tolerated. This highlights a possible treatment option for patients who do not respond to UDCA and obeticholic acid. The future for PBC seems to be combination drugs and approaches that aim for patients to get as near normal tests as possible.
Dr. Marlyn Mayo presented results from an analysis of patients who received Seladelpar, a possible future treatment for PBC, as part of an ongoing phase 2 clinical trial. This analysis reported that Seladelpar improved blood markers of cholestasis in patients with cirrhosis and in patients without cirrhosis. Patients with and without cirrhosis both showed no increase in itch and Seladalpar was well-tolerated in both groups. These findings emphasize that Seladelpar is effective and safe in cirrhotic and non-cirrhotic patients. Seladelpar may be the next new approved drug for PBC; there is a big late stage trial ongoing now, which includes sites across the world and including in Canada.
Excerpt from Seladelpar presentation highlighting some of its important qualities
Dr Chris Bowlus and Dr. Andreas Kramer presented results of a 3-year study of patients treated with obeticholic acid. Their study showed that after 3 years, the majority of patients had improvement or no progression of liver fibrosis, had no progression in bile duct loss, and that markers of cholestasis and inflammation had gotten significantly better. They highlighted obeticholic acid as a promising treatment. Many Canadian patients are on obeticholic acid already (see below for the report of the Canadian experience of OCA).
A session for doctors on how to manage their patients’ itch highlighted the impact that itch can have on patients’ quality of life. Approximately 35% of patients report persistent itch, either frequently or all the time. The current treatments for itch were discussed, namely cholestyramine and rifampicin. The positive effects of bezafibrate on itch were highlighted, which may be a new way to manage itch in the future.
Other Noteworthy Results
- Marilyn J Mayo presented results demonstrating that obeticholic acid is safe and effective in patients with PBC and Autoimmune hepatitis overlap syndrome.
- Cynthia Levy presented results demonstrating patients treated with obeticholic acid had reduced levels of HDL and total cholesterol but highlighted the need for more studies to confirm this.
- Gideon Hirschfield presented results demonstrating that long-term treatment with obeticholic acid helps slow the progression of PBC and improved blood markers of inflammation and immune system health.
- Jessica Dyson presented results from the United Kingdom showing that patients with PBC are disproportionately located in areas with coal mining activity. This was interesting because it reminded us that it is our genes and our environments that cause diseases like PBC.
- Surain Roberts presented results from Toronto about the effectiveness of obeticholic acid prescribed outside of clinical trials. Results showed that obeticholic acid improved blood markers of cholestasis and inflammation consistent with results reported by clinical trials. These results further support obeticholic acid as an effective therapy for PBC.
Fiorella Murillo presented a decision-making framework that clinicians can use to decide when to refer their patients with PBC to a specialist. This may help better identify patients who need to be referred to a specialist.
Surain Roberts presented results about treatment goals for patients with Autoimmune Hepatitis from the Canadian Network for Autoimmune Liver disease (CaNAL). Stay tuned for PBC-related results from this national study in the future!
There were some noteworthy presentations not about PBC but which are of interest as they inform patients with PBC of things for the future. First and foremost, the conference had a lot of new studies about a disease called non-alcoholic fatty liver disease (NAFLD). This is going to be the most common liver disease worldwide because it is most often associated with being overweight. There were many talks about how to tackle this both through better awareness as well as lifestyle changes (diet and exercise). As this was a liver treatment conference, there were also results of trials of drug therapy. For the PBC community, it is noteworthy that many of the drugs in development for PBC are also being developed for NAFLD, or at least the sub-group of patients with NAFLD who have inflammation and scarring in their liver. This is because the science behind inflammation in the liver seems to share similarities between different diseases. Drugs such as Obeticholic acid, Seladelpar and the Genfit drug, all used in PBC either in clinic or in trials, are also being developed for fatty liver. In particular, we heard the interim results of trying Obeticholic acid in fatty liver and heard how there was evidence from a large study that the drug seemed to reduce liver scarring.
Other highlights from ILC were about rare disease research and how rare disease communities can work together to make progress. An extremely rare disease called porphyria got a lot of attention, because a trial reported really quite amazing results of a special therapy that stops the wrong protein from being made in these patients. The results were dramatic and attracted global news. This report prepared for the Canadian PBC Society by Surain Roberts & Fiorella Murillo