MRC initiative is instrumental in getting new drug for rare liver disease approved
9 Nov 2017
This case study forms part of our Investing for Impact report, looking at how MRC- funded research delivers impact. More can be found in the Investing for Impact section of our website.
Scientists from the UK-PBC, an MRC Stratified Medicine Initiative, have been instrumental in getting the first new drug in 20 years for a progressive liver disease approved. Obeticholic acid, to treat primary biliary cholangitis (PBC), received FDA approval in 2016 and NICE approval in March 2017.
Primary biliary cholangitis (PBC) is thought to affect 20,000 people in the UK. Unfortunately, around 30% of patients with this condition do not respond to the current drug treatments available. For these patients, their liver disease becomes worse over time ultimately leading to irreparable damage through cirrhosis. At this point, their only option is a liver transplant. New treatments to tackle PBC in these high-risk individuals are therefore urgently needed.
The UK-PBC was set up through the MRC Stratified Medicine Initiative to provide a better understanding of why some patients respond to treatment and some don’t, and to identify, target, and evaluate new treatments. Led by Professor David Jones at the University of Newcastle, the UK-PBC is made up of researchers with expertise ranging from biochemistry, biological modelling, and statistical genetics to clinicians with expertise in liver disease and translational medicine. The UK-PBC team is based primarily in the north of England, with researchers based in Newcastle and Birmingham. It exemplifies how the MRC funds cutting-edge research where it occurs; either regionally- focused or across the entire UK.
The team conducted a Phase III clinical trial, in collaboration with industry partner Intercept Pharmaceuticals, the results of which were published in August 2016. The researchers undertook targeted patient recruitment through the UK-PBC cohort. The UK-PBC cohort is a valuable database of information from nearly 7,000 patients with PBC living in the UK, estimated to be approximately 40% of the PBC population in the country. The results demonstrated that a new treatment called obeticholic acid (OCA) improved PBC, and these effects were sustained for the two-year duration of the trial. The team submitted these results to the US Food and Drug Administration (FDA) Agency to provide evidence that there was unmet need in the disease, and to outline the patient impact of their work. As a result, an independent Advisory Committee voted 17 to 0 to support FDA approval of OCA which will now be the first new drug approved for use in PBC in 20 years. On March 2017, OCA also received NICE approval, one of the fastest approvals to date for an orphan medication.
As part of the MRC Stratified Medicine Initiative funding, the team were also interested in studying fatigue and cognitive issues, which are known side effects of PBC. Using mouse models of PBC, the team studied these cognitive effects and discovered that OCA could reverse brain injury in mice if given early in the disease, rather than as salvage therapy. These findings have exciting implications and the team are currently assessing them in patients with early disease to develop a human early intervention study.
"Funding from the MRC Stratified Medicine Initiative has quite simply transformed PBC. The support has allowed us to work with our patient partners in the PBC Foundation and LIVERNORTH to develop the largest and best characterised patient cohort in the world (7000 patients which equates to about 40% of all UK patients). Our work helped develop the first new treatment in PBC in a generation; OCA (Ocaliva), is now approved in Europe and the USA, with a pipeline of further treatments. These new treatments, the increased understanding of the disease, and the empowerment of patients who are equal partners in the enterprise mean that the use of the word transform is fully justified. We have shown that with the support of the MRC Stratified Medicine Initiative, therapy can be developed in rare diseases such as PBC. We think this provides an exciting model for how we can approach other rare diseases in the future" – Professor David Jones, UK-PBC Director, University of Newcastle
Award details: MR/L001489/1