Results of Exjade for Non-Transfused Patients Study
December 16, 2011 – Results from THALASSA, a placebo-controlled study examining the benefit of iron chelation with Exjade® (deferasirox) in patients with non-transfusion-dependent thalassemia (NTDT), were presented on December 13 at the 53rd Annual Meeting of the American Society of Hematology in San Diego. “Patients with NTDT” could include some individuals with beta thalassemia intermedia, hemoglobin H or e-beta thalassemia.
“Non-transfused patients can become iron overloaded simply from exuberant absorption of dietary iron,” explains CAF Medical Advisory Board Chair Ellis Neufeld, MD. “Because this route of iron loading is much slower and at a lower level than from transfusions, it takes decades to have a significant effect. As one would expect from the modest degree of iron intake, low doses of deferasirox (Exjade) can readily lower the body iron burden in thalassemia intermedia.”
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This recent clinical trial sponsored by Novartis has proven this point that was already well known to thalassemia treaters.
The study met its primary endpoint, showing that Exjade at a 10 mg/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 were nausea, rash, diarrhea, headache and upper abdominal pain. Adverse events were similar in all patient groups, including the placebo arm.
Dr. Neufeld recommends that adults with thalassemia intermedia have periodic assessment of iron status by MRI of the heart and liver. He says that if iron overload is progressive and substantial, relatively short courses of or deferasirox can remove the excess iron safely and effectively. Thalassemia intermedia patients should review their iron status lab studies and MRI with their hematologist to determine whether chelator therapy is indicated.
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
Exjade Important Safety Information
Exjade is contraindicated in patients with creatinine clearance <40 mL/min or serum creatinine >2 times the age-appropriate upper limit of normal; poor performance status and high-risk myelodysplastic syndromes or advanced malignancies: platelet counts <50 x 109/L; known hypersensitivity to deferasirox or any component of Exjade.
There have been postmarketing reports of acute renal failure, hepatic failure, and cytopenias. Renal failure requiring temporary or permanent dialysis, renal tubulopathy, and interstitial nephritis have been reported. Upper gastrointestinal ulceration and hemorrhage, sometimes fatal, have been reported. Caution should be used in elderly patients due to a higher frequency of adverse reactions. Exjade is not recommended in patients with a short life expectancy (e.g., high-risk myelodysplastic syndromes), especially when co-morbidities could increase the risk of adverse events.
Skin rashes, serious hypersensitivity reactions, decreased hearing, and lens opacities have been reported. The most common adverse reactions are nausea, vomiting, diarrhea, abdominal pain, rash, non‐progressive increases in serum creatinine, increased transaminases, abdominal distension, constipation, dyspepsia, proteinuria, and headache.