New data from the largest prospective trial in iron chelation demonstrate the efficacy and safety of Exjade® (deferasirox) in treating chronic transfusional iron overload, a potentially life-threatening condition for patients who have had multiple blood transfusions to treat underlying anaemias, including myelodysplastic syndromes (MDS).1,2
Data from this landmark trial, known as EPIC, were presented today at the 50th American Society of Hematology (ASH) Annual Meeting and Exposition in San Francisco, California.
A pre-planned analysis of 341 MDS patients enrolled in the study showed that Exjade significantly reduced levels of serum ferritin (SF), a key measure of iron in the body, by 253.0 ng/mL from baseline (P=0.0019). Of the 174 MDS patients whose SF was measured at one year, the decrease from baseline was 826 ng/mL.1
Myelodysplastic syndromes (MDS) are a group of blood disorders marked by overproduction of defective blood cells and a lack of healthy ones.
The MDS may be diagnosed at any age but they are rare in childhood and very uncommon in young adults. 3 MDS is more likely to affect men and over 90% of patients are over 50 years old at the time of diagnosis. 3
About 3,250 people in the UK are diagnosed with MDS each year. 4 Approximately one third of cases progress to acute leukaemia, a fatal blood cancer. 5
“Many MDS patients receive regular blood transfusions as part of their ongoing treatment, which puts them at risk for iron overload,” said EPIC study author Norbert Gattermann, MD, PhD, Hematology, Oncology and Clinical Immunology, Heinrich Heine University Medical Center, Dusseldorf, Germany. “This study, which includes the largest number of MDS patients of any iron chelation study, shows deferasirox can effectively reduce iron burden and is generally well tolerated when used appropriately to treat these patients.”
Most patients with MDS require supportive care in the form of regular blood transfusions to help prevent symptoms and complications of the disease. 6 However the consequence of these blood transfusions is iron overload as the body has no physiological means to remove iron. This iron overload is life-threatening and if left untreated causes significant tissue damage to organs such as the heart, liver and endocrine glands, and can ultimately lead to death. 7
Research demonstrates that iron overload puts MDS patients at greater risk of death8 and the British Journal of Haematology Guidelines state that transfusion-dependent patients with low-risk MDS and patients with documented stable disease should be chelated. 9
Prior to the approval of Exjade®, the most common way of performing iron chelation was with a treatment called desferrioxamine (DFO) and involved a painful nightly infusion by needle and pump that can last from eight to 12 hours every night for five to seven nights a week. 10,11 This treatment is demanding and inconvenient and can be particularly distressing for children and for their parents or carers who must administer the infusion.
As a result of the pain and inconvenience, many patients stopped or avoided iron chelation therapy, thus risking the toxic effects of iron overload. 12
Exjade® (deferasirox) has been awarded a prestigious UK Prix Galien award for innovative research and development in orphan drugs. Exjade, administered as a dissolvable tablet in a drink is the only once-daily oral drug that provides effective 24-hour iron chelation. The development of Exjade® was the result of more than 20 years of research, driven by the search for an effective oral iron chelator with a good tolerability profile that could transform the lives of patients by removing the need for lengthy, cumbersome and painful infusions.
References
1) Gattermann, N. Efficacy and safety of deferasirox (Exjade®) during 1 year of treatment in transfusion-dependent patients with myelodysplastic syndromes: Results from the EPIC trial. Poster presented at the 50th American Society of Hematology (ASH) Meeting, 6-9 December, San Francisco, CA, USA.
2) Cappellini, M. Efficacy and safety of deferasirox (Exjade®) in patients with transfusion-dependent anemias: 1-year results from the large, prospective, multicenter EPIC study. Poster presented at the 50th American Society of Hematology (ASH) Meeting, 6-9 December, San Francisco, CA, USA.
3) Myelodysplastic Syndromes. Leukaemia Research. Peer-reviewed patient information booklet available from Leukaemia Research at lrf/media/images/MDS_7049.pdf Last accessed on 02.12.08
4) MDS Disease Information. Leukaemia Research . Available at lrf/en/1/dismdshome.html Last accessed: 02.12.08
5) Mufti GJ, Bennett JM, Goasguen J, et al. Diagnosis and classification of myelodysplastic syndrome: International Working Group on Morphology of myelodysplastic syndrome (IWGM-MDS) consensus proposals for the definition and enumeration of myeloblasts and ring sideroblasts. Haematologica 2008; 93:1712-1717. doi: 10.3324/haematol.13405
6) Besa E. Myelodysplastic Syndrome. eMedicine. Available at: emedicine/med/topic2695.htm Last accessed: 02.12.08.
7) Piga A, Galanello R, Forni GL et al. Randomized phase II trial of deferasirox (Exjade, ICL670), a once-daily, orally-administered iron chelator, in comparison to deferoxamine in thalassemia patients with transfusional iron overload. Haematologica 2006;91:873-880.
8) Malcovati L, Porta MG, Pascutto C, et al. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol. 2005;23:7594-7603.
9) Bowen D, Culligan D, Jowitt S et al. Guidelines for the Diagnosis and Therapy of Adult Myelodysplastic Syndromes. British Journal of Haematology, 2003; 120: 187-200
10) Desferal: Summary of Product Characteristics. Novartis.
11) Nisbet-Brown E, Olivieri NF, Giardina PJ et al. Effectiveness and safety of ICL670 in iron-loaded patients with thalassaemia: a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet 2003;361:1597-1602.
12) Modell, B et al. Survival in ß-thalassaemia major in the UK: data from the UK Thalassaemia Register. Lancet 2000; 355:2051-2052.
13) Exjade: Summary of Product Characteristics. September 2008, Novartis Pharmaceuticals UK Ltd.
14) Cappellini et al. A Phase III study of deferasirox (ICL670), a once-daily oral iron chelator in patients with beta thalassaemia. Blood, 1 May 2006.Volume 107, Number 9.
About the studies
About the EPIC trial
The EPIC trial was a one-year, open-label, prospective, multicentre trial. EPIC studied the efficacy and safety of a fixed starting dose of Exjade based on transfusional iron intake, with subsequent dose titration at 3-monthly intervals based on serum ferritin (SF) trends. With 1,744 patients, this trial is the largest ever conducted for an iron chelator and included the largest cohorts of underlying anaemias in a single trial, including patients with beta-thalassaemia, MDS and aplastic anaemia. Twelve abstracts from EPIC are being presented at ASH.
Study details
[Abstract: 633] [N Gattermann, et al.]1
This pre-planned subgroup analysis of the EPIC study included 341 patients with transfusion-dependent MDS and SF levels ≥1000 ng/mL, or SF 20 transfusions or 100 mL/kg of red blood cells) and an R2 MRI-confirmed LIC >2 mg Fe/g dw. Overall, mean actual dose of Exjade over one year of treatment was 19.2±5.4 mg/kg/day. Based on the last observation carried forward statistical method, at one year, there was a significant reduction in median SF from baseline (253.0 ng/mL; P=0.0019, n=341). Of the 174 MDS patients whose SF was measured at one year, the decrease from baseline was 826 ng/mL. Overall, 48.7% of pts (n=166) discontinued therapy. Most common investigator-assessed drug-related adverse events were mild to moderate in severity and included diarrhoea (n=110, 32%), nausea (n=45, 13%), vomiting (n=26, 8%), abdominal pain (n=26, 8%), upper abdominal pain (n=25, 7%), rash (n=23, 7%) and constipation (n=21, 6%).1
About Exjade
Exjade (deferasirox) is the first and only once-daily oral iron chelator approved for the treatment of transfusion iron overload. Developed as an alternative to desferrioxamine, it is the only chelator to demonstrate continuous 24 hour chelation of excess iron with a single oral daily dose. 13
Administered as a drink, Exjade is expected to transform the treatment of iron overload by making iron chelation more acceptable to patients. In a pivotal phase three study, part of the largest ever clinical trials programme for an iron chelator, it proved to be as effective as desferrioxamine in patients receiving higher doses of the drug.14 Exjade provides an alternative to time-consuming, frequent and often painful treatment and gives patients a well-tolerated, effective and convenient treatment option.
About Novartis
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