Study Shows Once-Daily Exjade Removes Iron From The Heart In Transfused Patients With Beta-thalassaemia

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Interim study results show that once-daily Exjade® (deferasirox) reduces iron that can build up in key organs in patients who undergo repeated blood transfusions as part of their treatment for thalassaemia. Approximately 78% of patients treated with Exjade had decreases in cardiac iron (measured by any change in T2*(i), a magnetic resonance imaging measurement of myocardial iron) and 89% of patients had decreases in liver iron after six months of treatment (measured by decreases in liver iron concentration levels).1

In addition, new long-term data from two other studies show that thalassaemia patients benefit from treatment with Exjade. At two years, in a study of 247 patients, Exjade significantly reduced iron toxicity in patients who had been previously treated with the alternative iron chelators desferrioxamine and/or deferiprone.2,4 Results from a separate analysis of 680 heavily transfused thalassaemia patients support the efficacy and safety of Exjade seen over 3.5 years.3

The three studies described above were reported at the 11th International Conference on Thalassaemia Hemoglobinopathies and at the 13th International Thalassaemia International Federation (TIF) Conference for Thalassaemia Patients and Parents in Singapore.

“Removing iron from the heart and other organs is critical in transfused patients with beta-thalassaemia due to the potential for significant organ damage by the build up of iron in the body”, said Dr Farrukh Shah, Consultant Haematologist, Whittington Hospital, London. “These data reinforce the strong profile of Exjade which is not only an effective iron chelator but significantly improves patient quality of life and acceptance of iron chelation due to its unique once-daily, oral formulation.”

Regular blood transfusion therapy is essential for patients with chronic anaemias such as beta-thalassaemia, and may be necessary in diseases such as sickle cell disease (SCD) and myelodysplastic syndromes (MDS), in order to improve quality of life and survival. 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.5

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.6,7 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.8 Indeed, it is estimated that as recently as 2000, around 50% of UK patients with beta-thalassaemia died before the age of 35, mainly because conventional iron chelation therapy is too burdensome for full adherence.8

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.


1) Wood J, et al. Deferasirox (Exjade®) reduces cardiac iron burden in β-thalassemia patients with transfusional iron overload: An MRI T2* study. Reported at the 11th International Conference on Thalassaemia Haemoglobinopathies and the 13th International TIF Conference for Thalassaemia Patients and Parents in Singapore. Abstract ID: CHE41.

2) Taher A, et al. Efficacy and safety of once-daily oral deferasirox (Exjade®) during 2 years of treatment in heavily iron-overloaded patients with thalassemia. Reported at the 11th International Conference on Thalassaemia Haemoglobinopathies and the 13th International TIF Conference for Thalassaemia Patients and Parents in Singapore. Abstract ID: FC15.

3) Porter J, et al. Long-term efficacy and safety of deferasirox (Exjade®), a once-daily oral iron chelator, in patients with β-thalassemia: results of 3.5-year follow up. Reported at the 11th International Conference on Thalassaemia Haemoglobinopathies and the 13th International TIF Conference for Thalassaemia Patients and Parents in Singapore. Abstract ID: FC12.

4) Taher, A. Efficacy of the once-daily oral chelator deferasirox (Exjade®) in β-thalassemia patients by baseline liver iron concentration (LIC): Results from ESCALATOR study. Reported at the 11th International Conference on Thalassaemia Haemoglobinopathies and the 13th International TIF Conference for Thalassaemia Patients and Parents in Singapore. Abstract ID: CHE40.

5) 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.

6) Desferal: Summary of Product Characteristics. Novartis

7) 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

8) Modell, B et al. Survival in ß-thalassaemia major in the UK: data from the UK Thalassaemia Register. Lancet 2000; 355:2051-2052

9) Exjade: Summary of Product Characteristics. September 2008, Novartis Pharmaceuticals UK Ltd.

10) 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

[Abstract ID: CHE41] [J Wood, et al.]1

This is an 18-month, multi-center study of 30 β-thalassaemia patients with evidence of high myocardial iron. Serum ferritin, (SF), a key measure of iron overload, was assessed monthly and iron levels in the heart and liver were assessed every six months. Six month results for 18 evaluable patients showed that Exjade, dosed at 30-40 mg/kg/day, decreased cardiac iron in 78% of patients. Cardiac iron results were measured by any change in T2*, a magnetic resonance imaging measurement of myocardial iron. Additionally, 90% of patients had reductions in liver iron as measured by decreases in liver concentration levels (LIC).

[Abstract ID: FC15] and [Abstract ID: CHE40] [A Taher, et al.]2,4

The ESCALATOR trial evaluated the effectiveness of Exjade in heavily iron-overloaded β-thalassaemia patients who had been previously treated with desferrioxamine and/or deferiprone. The one-year core study evaluated the efficacy and safety of Exjade in 252 patients with a starting dose of 20 mg/kg/day (except for three patients who started at 10 mg/kg/day). Seventy-six percent of patients required dose increases to 25/30 mg/kg/day after a median of 24 weeks to achieve their therapeutic goals. A one-year extension study continued to evaluate the safety and efficacy of deferasirox in 247 patients who had completed the one-year core and were interested/eligible to continue in the extension.

LIC decreased from 19.2 to 15.8 in the core study and to 13.2 at the end of the one – year extension. Approximately 38% of patients on deferasirox had an LIC below 7 mg/Fe/g d w compared to 9.3% at the start of the trial. Additionally, SF levels decreased from 3395 g/L at the beginning of the study to 2247 g/L at two years (change from baseline – 929 g/L p< 0.0001). The study showed a low discontinuation rate and clinically manageable safety profile. 96% of patients completed two years of treatment.

[Abstract ID: FC12] [J Porter, et al.]3

A pooled interim analysis of data from three ongoing extension trials evaluated efficacy and safety in 680 β-thalassaemia patients over 3.5 years. Results showed that deferasirox administered at 20 /mg/kg/day maintained serum ferritin levels while 30 mg/kg/day doses showed a statistically significant reduction in serum ferritin levels at study end. Over 3.5 years, deferasirox showed efficacy in reducing transfusional iron toxicity while highlighting the importance of dose titration in heavily transfused β-thalassaemia patients. Deferasirox was generally well tolerated.

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. 9

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.10 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

Novartis AG (NYSE: NVS) is a world leader in offering medicines to protect health, cure disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. Novartis is the only company with leadership positions in these areas. In 2006, the Group’s businesses achieved net sales of USD 37.0 billion and net income of USD 7.2 billion. Approximately USD 5.4 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 100,000 associates and operate in over 140 countries around the world.


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