A new UK clinical trial will “supercharge” patients’ own immune cells to help their livers recover.
The EMERALD trial (Evaluating Macrophages Engineered to Resolve Advanced Liver Disease), will see if people with advanced liver cirrhosis can benefit from an experimental cell therapy.
People with severe liver cirrhosis will receive altered versions of one of their own immune cells, called macrophages. Macrophages are a type of white blood cell. They have a variety of roles. These include killing bacteria, removing dead cells and helping organ repair.
For the study, patients’ own macrophages will be improved in a lab to help reduce and prevent further scarring in their damaged liver.
Every year more than 4,000 people in the UK die of end-stage liver disease. Including hundreds who do so while waiting for a transplant.
The hope is that the engineered cells will improve patient’s health. So they can avoid major health events or the need for a liver transplant.
Promising early results
UK-based company Resolution Therapeutics has just received approval from the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) for the trial to begin. It builds on promising results from the earlier MATCH study. This used non-engineered macrophages and has been running for the last three years in Scotland.
You can read our blog about the early results of the MATCH study here.
The MATCH team presented new data at a recent major medical conference, the European Association for the Study of the Liver (EASL) Congress in Milan, Italy. They compared people who received the new therapy with people who had standard care. They found that people who received the macrophages:
- were more likely to still be alive two and a half years after the trial started
- were less likely to have needed a liver transplant
Professor Stuart Forbes, a prominent hepatologist at the University of Edinburgh and the principal investigator of the MATCH study, has been studying the role of macrophages in liver disease over the past 10 years. He said:
We are greatly encouraged by the data from the MATCH study and this long term follow up study.
Professor Forbes is also a co-founder of Resolution Therapeutics.
New study
EMERALD will take things a step further by engineering each patient’s macrophage cells in the lab before they are returned to them.
Dr Clifford Brass, Chief Medical Officer of Resolution Therapeutics explained why the engineering is important:
We want to improve patients’ macrophages in two ways. Firstly, we want to make them more potent by boosting their anti-inflammatory and anti-fibrotic potential. Secondly, we want to make them last longer in the body.
In a recent webinar hosted by Resolution Therapeutics, Professor Arun Sanyal, a world renowned hepatologist from Virginia Commonwealth University in the US, said:
[If the EMERALD shows the same effect as the MATCH study but in decompensated patients], it would really be a game changer. It would give an option for patients to live longer and have better quality of life.
The new therapy holds out hope for people whose cirrhosis is so severe that their liver has stopped working properly. This is called “decompensated” cirrhosis.
The aim of the new treatment is to return decompensated livers to a “compensated” state. Despite being scarred, a liver with compensated cirrhosis can carry out essential functions. Like filtering blood and breaking down toxins.
Dr Brass said he was “excited” the Phase I/II EMERALD study had been given the go-ahead by the MHRA.
EMERALD is expected to start enrolling patients before the end of 2024. The study will take place in hospitals across the UK and Spain. We will update our information about the trial once the full list of hospitals is announced. The list will also be published on clinicaltrials.gov.
