Novartis has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for Exjade® (deferasirox) for the treatment of chronic iron overload requiring chelation therapy when deferoxamine therapy is contraindicated or inadequate in patients aged ten years and older with non-transfusion-dependent thalassemia (NTDT) syndromes. Exjade would be the first oral treatment in the European Union (EU) specifically indicated for the treatment of iron overload in patients with these types of thalassemia.
Results from the first prospective placebo-controlled study of iron chelation in NTDT patients, THALASSA, showed a significant dose-dependent decrease in iron burden compared to placebo. In this pivotal study, Exjade was well tolerated, with an overall adverse event rate similar to the placebo arm.
Thalassemia refers to a diverse group of genetic disorders that affect red blood cell production, causing anaemia. Unlike patients with other types of thalassemia, those with NTDT syndromes can live without regular transfusions, a significant cause of iron overload. However, even without transfusions, NTDT patients still accumulate excess iron through intestinal absorption, leading to debilitating health complications like liver fibrosis and cirrhosis, blood clots, bone disease, pulmonary hypertension and vascular and endocrine diseases.[2,3]
“Patients with NTDT have suffered the effects of iron overload without accurate diagnosis, clear treatment guidelines or specifically approved oral therapies,” said Hervé Hoppenot, President, Novartis Oncology. “The CHMP recommendation is an important step toward improving the outcomes of patients with this type of thalassemia.”
According to published studies, at least three quarters of a million people worldwide have NTDT syndromes, although as understanding of the disease increases, it is probable the number will grow.[4–6] Because NTDT patients are not symptomatic at birth, when most thalassemias are diagnosed, they are often underdiagnosed and underrated. Many complications associated with iron overload begin to appear as early as age ten and become increasingly common as patients reach their 20s or 30s. Most NTDT patients are of South and Southeast Asian, Mediterranean or Middle Eastern origin, with immigration broadening the global prevalence.[7,9]
The European Commission generally follows the recommendations of the CHMP and usually delivers its final decision within three months of the CHMP recommendation. The decision will be applicable to all 27 EU Member States plus Iceland and Norway. Exjade has been approved to treat chronic iron overload in patients with NTDT in Canada and several other countries; further regulatory submissions are ongoing.
Exjade is an oral iron chelation therapy indicated for the treatment of chronic iron overload due to frequent blood transfusions (>=7 ml/kg/month of packed red blood cells) in patients with beta thalassemia aged six years and older). It is also indicated for the treatment of chronic iron overload due to blood transfusions when deferoxamine therapy is contraindicated or inadequate in the following patient groups: patients with beta thalassemia major with iron overload due to frequent blood transfusions (>=7 ml/kg/month of packed red blood cells) aged two to five years; patients with beta thalassemia major with iron overload due to infrequent blood transfusions (<7 ml/kg/month of packed red blood cells) aged two years and older; and patients with other anaemias aged two years and older.
It is approved in more than 100 countries including the US, Switzerland, Japan and countries comprising the EU. The approved indication may vary depending upon the individual country.
- Taher A, Porter J, Viprakasit V, et al. Deferasirox significantly reduces iron overload in non-transfusion-dependent thalassemia: 1-year results from a prospective, randomized, double-blind, placebo-controlled study. Blood. 2012. Published online before print May 15, 2012.
- Musallam KM, Cappellini MD, Wood JC, et al. Iron overload in non-transfusion-dependent thalassemia: a clinical perspective. Blood Reviews. 2012:26S:S16-S19.
- Musallam KM, Cappellini MD, Wood JC, Motta I, Graziadei G, Tamin H, Taher AT. Elevated liver iron concentration is a marker of increased morbidity in patients with ß thalassemia intermedia. Haematologica. 2011 Nov;96(11):1605-12.
- Vichinsky E. Hemoglobin E syndromes. Hematology Am Soc Hematol Educ Program. 2007;79-83.
- Weatherall DJ. The definition and epidemiology of non-transfusion-dependent thalassemia. Blood Reviews. 2012:26S:S3-S6.
- Vichinsky EP. Changing patterns of thalassemia worldwide. Ann NY Acad Sci. 2005;1054:18-24.
- Thalassaemia International Federation. The Thalassaemia International Federation’s (TIF) New Focus: Addressing the Management of Non-Transfusion-Dependent Thalassaemias (NTDT). Position Paper 5.2. March 20, 2012. Accessed at: http://www.thalassaemia.org.cy/pdf/NTDT_Position_Paper_Final.pdf.
- Taher AT. Age-related complications in treatment-naïve patients with thalassemia intermedia. Brit J Haematol. 2010;150:486-489.
- Taher A, Cappellini MD, Musallam KM. Recent advances and treatment challenges in patients with non-transfusion-dependent thalassemia. Blood. 2012;26S:S1-2.
- EMC. Summary of product characteristics: EXJADE 125 mg, 250mg, 500mg dispersible tablets. Last updated January 13, 2012. Accessed at: http://www.medicines.org.uk/emc/medicine/18805.