The European Commission has approved Novartis' Exjade (deferasirox) for the treatment of chronic iron overload requiring chelation therapy when deferoxamine therapy is contraindicated or inadequate in patients aged 10 years and older with non-transfusion-dependent thalassemia (NTDT) syndromes.

Exjade is the first oral treatment approved in the European Union (EU) specifically indicated for the treatment of chronic iron overload in patients with these types of thalassemia.

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.

"NTDT syndromes can be complicated to manage. Without proper treatment, patients with NTDT can suffer severe and life-changing complications from chronic iron overload," said Professor Maria Domenica Cappellini, MD, Department of Internal Medicine, University of Milan. "The Thalassa data show that these patients now have an effective oral treatment option to help reduce iron concentration in the body."

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 receive 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.

"This approval is a critical milestone for patients with NTDT syndromes," said Hervé Hoppenot, president, Novartis Oncology. "For the first time, Exjade will be available to thalassemia patients who are not regularly transfused but still suffer from the life-altering effects of excess iron."

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 10% in any Exjade or placebo group) were headache, upper respiratory tract infection, oropharyngeal pain, pyrexia, rash and diarrhea.

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 6 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 2 to 5 years; patients with beta-thalassemia major with iron overload due to infrequent blood transfusions (<7 ml/kg/month of packed red blood cells) aged 2 years and older; and patients with other anemias aged 2 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.

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.