Novartis pivotal study of Exjade shows significant reduction of iron overload in patients with non-transfusion-dependent thalassemia

Basel, December 13, 2011 - Results from THALASSA, the first pivotal placebo-controlled study examining the benefit of iron chelation with Exjade® (deferasirox) in patients with non-transfusion-dependent thalassemia (NTDT), show that Exjade can significantly reduce iron overload. These data were presented today at the 53rd Annual Meeting of the American Society of Hematology in San Diego.

THALASSA investigated whether patients with NTDT and iron overload can benefit from iron chelation therapy as determined by liver iron concentration (LIC). The study met its primary endpoint, showing that Exjade at a 10mg/kg/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 on placebo (p<0.001). The study also determined that a 10 mg/kg/day dose was superior to a 5 mg/kg/day dose (p=0.009).

In the 10 mg/kg arm, 49% of patients had a LIC decrease of at least 30% from baseline versus only 2% in the placebo arm. In addition, 56% of patients in the 10 mg/kg arm had a LIC decrease of ≥3 mg at one year compared to 11% in the placebo arm. The most common adverse events reported werenausea, rash, diarrhea, headache and upper abdominal pain.[1]Adverse events were similar in all patient groups, including the placebo arm.[1]   

Thalassemia refers to a diverse group of genetic disorders that affect red blood cell production, causing anemia. Unlike types of thalassemia in which patients require regular blood transfusions, NTDT patients can live without frequent transfusions. However, patients with NTDT are still at risk of accumulating excess iron.[2]

"Results from THALASSA show that Exjade is effective in reducing liver iron levels in patients with NTDT," said Ali Taher, the lead study investigator and Professor of Medicine, Division of Hematology and Oncology, American University of Beirut Medical Center, Lebanon. "Iron chelation therapy is the only option for decreasing these patients' iron burden. These are significant findings for patients with a major unmet need."[1]

NTDT refers to a group of clinically milder forms of thalassemias, including beta-thalassemia intermedia[3], Hemoglobin H disease (Hb H-alpha-thalassemia)[4] and Hemoglobin E/beta-thalassemia.[5] Despite a slower rate of iron accumulation, the burden of iron overload in NTDT patients is similar to that observed in thalassemia patients who receive regular blood transfusions. NTDT patients are not symptomatic at birth, when most thalassemias are diagnosed. Therefore they are often underdiagnosed and untreated even when symptoms appear at age 10 or later. NTDT is most commonly found in Southeast Asian, South Asian, Middle Eastern and Mediterranean populations.

"Over the past six years, Exjade has provided thalassemia patients an effective option for the treatment of chronic iron overload due to blood transfusions," said Hervé Hoppenot, President, Novartis Oncology. "These new clinical trial data show that Exjade may also benefit NTDT patients who often are at risk for serious health complications."

Regulatory submissions for Exjade based on the THALASSA results are planned by the end of 2011.


Study details

The THALASSA study assessed the efficacy of Exjade versus placebo in NTDT patients ≥10 years of age with iron overload.  

THALASSA was a one-year, randomized, double-blind, placebo-controlled pivotal study, including 166 patients with beta-thalassemia intermedia (n=95), alpha-thalassemia (n=22) or Hemoglobin E/beta-thalassemia (n=49). Patients ≥10 years of age with LIC ≥5 mg Fe/g dw and serum ferritin >300 ng/mL were randomized to starting Exjade doses of 5 mg/kg/day (n=55) or matching placebo (n=28) and 10 mg/kg/day (n=55) or matching placebo (n=28).[1]


About Exjade

Exjade is indicated for the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in adult and pediatric patients (aged 2 years and over). It is approved in over 100 countries including the US, Switzerland, Japan, and the countries comprising the European Union. The approved indication may vary depending upon the individual country.