The US Food and Drug Administration (FDA) has approved Novartis' Exjade (deferasirox) for the treatment of chronic iron overload in patients 10 years of age and older with non-transfusion-dependent thalassemia (NTDT) syndromes and with a liver iron concentration of at least five mg of iron per gram dry weight and a serum ferritin measurement greater than 300 micrograms per liter. Exjade is the first treatment indicated for patients with these types of thalassemia in the United States.

The approval is based on results from the first prospective placebo-controlled study of iron chelation in NTDT patients, THALASSA, which showed a significant dose-dependent decrease in iron burden compared to placebo (p<0.001). In this pivotal study, Exjade significantly reduced the concentration of iron in the liver, known as liver iron concentration (LIC), as well as the amount of iron anywhere in the body, measured by serum ferritin. The overall adverse event rate for Exjade was similar to the placebo arm.

"Patients with NTDT can suffer severe and life-changing complications from chronic iron overload," said Elliott Vichinsky, MD, medical director, Hematology/Oncology, Children's Hospital and Research Centre, Oakland, California. "In these thalassemia patients, excess iron starts to accumulate at birth yet is often undetected until serious symptoms appear in early adulthood. With this approval of Exjade, physicians will be able to offer NTDT patients a treatment option, helping fulfill a critical unmet need."

Thalassemia refers to a diverse group of genetic disorders that affect red blood cell production, causing anemia. Unlike patients with other types of thalassemia, those with NTDT syndromes don't require regular transfusions, a significant cause of chronic 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.

"For years, Exjade has effectively treated chronic iron overload in transfused thalassemia patients," said Alessandro Riva, Global Head, Oncology Development and Medical Affairs, Novartis Oncology. "Now, for the first time, thalassemia patients who do not receive regular transfusions but suffer the same debilitating effects from chronic iron overload, have an approved treatment option."

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. Because NTDT patients are not symptomatic at birth, when most thalassemias are diagnosed, they are often underdiagnosed and undertreated. Many complications associated with chronic iron overload begin to appear as early as age 10 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.

The THALASSA trial showed that Exjade at a 10 mg/kg per day starting dose significantly reduced LIC from baseline by 3.8 mg of iron per gram of liver dry weight (Fe/g dw) compared to an increase of 0.38 mg Fe/g dw in patients receiving placebo after 52 weeks of treatment (p<0.001). The study also determined that a 10 mg/kg per day dose was superior to a 5 mg/kg per day dose (p=0.009). Additional research has also demonstrated Exjade continues to provide benefit over the longer term, with LIC levels reduced by 7.14 mg Fe/g dw from baseline after 24 months of treatment. The most common reported adverse events (at least five per cent in any Exjade or placebo group) were nausea, skin rash, diarrhoea and headache.

In the US, Exjade is now indicated for the treatment of chronic iron overload in patients 10 years of age and older with non-transfusion-dependent thalassemia (NTDT) syndromes and with a liver iron concentration (LIC) of at least five mg of iron per gram dry weight (mg Fe/g dw) and a serum ferritin measurement greater than 300 micrograms per liter. The basis of this indication is data showing achievement of an LIC less than five mg Fe/g dw after treatment with Exjade. An improvement in survival or disease-related symptoms has not been established. Since 2005, Exjade has been approved in the US for the treatment of chronic iron overload due to blood transfusions in adult and pediatric patients (aged two years and over).

In the European Union (EU), 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 anemias aged two years and older. Exjade is also indicated for the treatment of chronic iron overload requiring chelation therapy when deferoxamine therapy is contraindicated or inadequate in patients with non-transfusion-dependent thalassemia syndromes aged 10 years and older.

Exjade is approved in over 100 countries including the US, Switzerland, Japan and countries comprising the EU. The approved indication may vary depending upon the individual country.