FDA Oks Deferasirox for Nontransfusion-Dependent Thalassemia

Megan Brooks

January 23, 2013

The US Food and Drug Administration (FDA) has expanded the approved use of deferasirox (Exjade, Novartis) to treat patients aged 10 years and older with chronic iron overload due to nontransfusion-dependent thalassemia (NTDT), the agency announced today.

"Using our accelerated approval process, FDA is able to expedite the availability of this drug to patients who need to reduce excess iron," Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, said in a statement.

Deferasirox is the first drug approved to treat patients with NTDT who show iron overload.

The drug was approved in the United States in 2005 for treatment of chronic iron overload due to blood transfusions in patients aged 2 years and older. Today's approval extends its use to treat patients with NTDT who show iron overload. Deferasirox is indicated in patients with NTDT who have a liver iron concentration (LIC) of at least 5 milligrams of iron per gram of dry liver tissue weight, the FDA says.

NTDT is a milder form of thalassemia that does not require individuals to get frequent red blood cell transfusions. However, over time, some patients with NTDT are still at risk for iron overload that can lead to organ damage. The FDA has also authorized marketing of FerriScan (Resonance Health, Australia) as a companion MRI diagnostic for deferasirox.

The FDA says that deferasirox was approved on the basis of 2 clinical trials that showed it can reduce LIC to less than 5 mg/g dry weight, "a surrogate endpoint that is judged reasonably likely to predict a clinical benefit to patients."

In the first trial, 166 patients were randomly assigned to receive 5 or 10 mg/kg deferasirox or placebo daily. The results showed that 15% of patients on the lower dose and 27% of those on the higher dose achieved the target LIC compared with 4% of placebo-treated patients.

The second trial included 133 patients from the first study who received an additional year of deferasirox or switched from placebo to deferasirox. In this extension trial, 35% of evaluable patients achieved the target LIC.

The FDA's authorization of FerriScan was based largely on data from the trials that used FerriScan LIC results as the primary outcome measure. In addition, investigators conducted a 230-patient study that found that FerriScan results were as accurate as liver biopsy for measuring LIC, the FDA says.

"The FerriScan device is a noninvasive test that helps physicians to select appropriate patients for Exjade therapy as well as monitor their response to the drug, and discontinue therapy when LIC reaches safe levels," Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA's Center for Devices and Radiological Health, said in a statement.

An estimated 1000 people in the United States have thalassemia, according to the National Heart, Lung, and Blood Institute.