Impact Summary

Liver biopsies are invasive, risky and painful. An MRI based non-invasive technology has replaced liver biopsies in patients requiring repeated measurement of the concentration of iron in their liver. The non-invasive procedure developed from The University of Western Australia’s (UWA) research is associated with almost no risk to the patient while the invasive procedure is associated with risks of significant pain, bleeding, bile leak, and death. To date, over 45,000 patient measurements have been made using the new non-invasive method which has been incorporated into clinical guidelines for the management of diseases such as thalassaemia.

Impact Case Study

An overload of iron in the body can be lethal at high levels. People who receive multiple blood transfusions to treat conditions like thalassaemia, sickle cell anaemia, Diamond Blackfan anaemia, myelodysplastic syndrome, and some cancers might develop iron overload because the body has no mechanism for getting rid of excess iron. Doctors can reduce total body iron levels using drugs called chelators but need correct dosage and frequency, otherwise the very drugs intended to help can lead to toxicity.

The research carried out at UWA comprised developing a magnetic resonance imaging (MRI) based method for measuring liver iron concentration (LIC), testing and calibrating the method, improving the performance of the method, validating the method in an independent sample, and investigating the impact of the method on clinical decision making and patient outcomes. The methods and technology developed during the research were patented. The technology was commercialised by setting up a private company to which UWA assigned the intellectual property rights in return for a shareholding. Private investors invested cash in the company; Resonance Health, in return for shareholding. The company commercialised the technology as FerriScan®, gaining regulatory approvals for marketing in the USA, Europe, and Australia in 2005.

Market growth and maturity for ferriscan

Currently the technology is being used in approximately 250 hospitals in 39 countries around the world with over 30,000 patient measurements having been by the close of 2016. The numbers of centres using the technology and patients being measured per month has steadily increased between 2011 and 2016.

We are immensely proud that a technology initially developed at UWA is helping so many people, and that Resonance Health, a local company formed in Perth, has been able to turn this technology into a commercial success and build such a global footprint.

Sander Bangma, General Manager, Resonance Health, 2016.

Market growth has been tied to the research reputation brought by the UWA research underpinning the technology. Ferriscan is internationally recognised as the gold standard in LIC measurement. Published clinical guidelines on the management of iron overload in thalassaemia and sickle cell disease now recommend annual measurement of liver iron concentration (LIC) by MRI.

Pain-free measurement

Ferriscan provides a pain-free, non-invasive accurate measurement of liver iron concentration. Before the advent of FerriScan, patients were required to undergo an invasive biopsy procedure to remove a sample of their liver for chemical analysis. In comparison, Ferriscan requires a ten minute MRI. Results, analysed by Resonance Health staff, are available in two business days. FerriScan analysis provides proven accuracy, reliability and reproducibility over time and across different models of MRI scanners and not results are not affected by the comorbidities of fat, inflammation, or fibrosis.

I … would recommend FerriScan to anyone… The scans have helped monitor and plan my treatment. I certainly wouldn’t have wanted to have a liver biopsy.

John Falconer Perth haemochromatosis patient.

Better patient management

Ferriscan has allowed more frequent assessment of body iron burden and this has resulted in better management of patients. Regular blood transfusions cause the body to overload with iron if not managed appropriately. The excess iron becomes lethal at high levels. Management of the iron overload involves the use of drugs to remove the excess iron. The most reliable method for determining the most appropriate dose of drug is through the measurement of liver iron concentration. Two independent studies of the introduction of FerriScan into clinical practice demonstrated that body iron burden was reduced in people being monitored by Ferriscan.

1. Forty people with hemolytic anaemias or ineffective hematopoiesis experienced an average drop in liver iron concentration in one year of being monitored with Ferriscan (6.8 to 4.8 mg Fe/g dry tissue (P=0.008)). Before monitoring, 14 people were considered to be at risk of cardiac disease and early death based on their LIC, but after monitoring this had dropped to only 5 people. (Brown, 2012)
2. A study of children with Sickle Cell disease (which requires chronic transfusions) showed that those who were monitored using Ferriscan, the median LIC improved from 13.2 to 7.9 mg/g dw (p =0.027) after 2.7 years. In this group, In 67.9% of the children, the clinical management was changed from simple transfusions to erythrocytapheresis, and these children experienced a LIC improvement from 13.1 to 4.3 mg/g dw (P < 0.001). Ferriscan impacted clinical care, with adjustments occurring to therapy and care in about 1/3 of Ferriscan measurements. (Stanley, 2016)

The improved body iron burden in these studies of clinical practice was attributed to better informed decision making owing to the availability of an accurate method of LIC measurement.

The Haemochromatosis Society is working with the providers of FerriScan, Resonance Health, to promote awareness of iron overload and improve health outcomes for people affected by this disease.

Margaret Rankin; Past President of Haemochromatosis Australia.

Chelator therapy

Iron overload is treated by drugs known as chelators. An adverse effect of chelator therapy can be chelator toxicity, which FerriScan helps to reduce. In 2012, Ferriscan was used to track the progress of treatment and determine dose changes to avoid overchelation in a clinical trial of 110 patients with non-transfusion dependent thalassaemia (NTDT) being treated with a Novartis’ new daily oral tablet – Exjade, generic name: deferasirox (Taher, 2012). The safe application of the drug in the trial using FerriScan resulted in both the drug being approved by the FDA for use in NTDT patients and FerriScan being approved by the FDA in 2013 as a companion diagnostic for Exjade when used for NTDT.

Associated Research:

The research was carried out under the leadership of Prof Tim St Pierre in the School of Physics at UWA. Pre2002 the research centred around developing a method of using a magnetic resonance imaging scanner to measure a dynamic magnetic property in human tissue known as “R2”. It was hypothesised that R2 would be associated with the concentration of iron in tissue and was first tested on post-mortem human tissue.

Later developments in 2004 enabled the measurements to take into account motion artefacts that are encountered in living tissue. The prototype technology, published 2005, was calibrated against measurements in biopsies of 105 subjects recruited through clinical colleagues at UWA (Prof Jeffrey and Prof Olynyk), and elsewhere.

During 2006 to 2009, St Pierre, in collaboration with clinical colleagues from around the Middle East and the pharmaceutical company Novartis, collected data from the FerriScan technology paired with liver iron measurements from biopsies from 233 subjects for a clinical validation of the calibration curve under varying clinical conditions such as different types of MRI scanner, different iron chelation drugs, different levels of liver fibrosis, different ages of patients. This showed that the calibration is robust against all of these variable factors. The results were published in 2014. During 2010, modifications were made to the technology to enable data acquisition to be made in a shorter period of time – reducing costs to hospitals.