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CHORI Scientists Establish Safety and Efficacy of New Drug Combination to Treat Iron Overload

November, 2012 – A new study just published in Blood Cells, Molecules and Diseases by CHORI scientists Ashutosh Lal, MD, Elliott Vichinsky, MD, and their colleagues, demonstrates for the first time that using a combination of two different drugs together, deferasirox (DFX) and deferoxamine (DFO), provides excellent safety and a significant reduction in whole body iron in patients with transfusion-dependent thalassemia.

“We’ve shown for the first time that DFX/DFO in combination can be used safely, and that the two drugs together can achieve large reductions in whole body iron at tolerable doses,” says Dr. Lal.
“We’ve shown for the first time that DFX/DFO in combination can be used safely, and together can achieve large reductions in whole body iron at tolerable doses.”

Thalassemia major is an inherited blood disorder in which the body can't replenish its own supply of blood. As a result, patients with thalassemia major are dependent on monthly blood transfusions for their survival. While life-sustaining, blood transfusions also result in iron overload an accumulation of iron in the body which becomes toxic.

"Iron overload is the main reason for early mortality in transfusion-dependent thalassemia," explains Dr. Lal. "Iron can accumulate in the liver and cause liver dysfunction, it can accumulate in the heart and heart function declines, it can accumulate in the pancreas and cause diabetes. The majority of complications in thalassemia are driven by iron accumulation."

Clinicians rely on a variety of different drugs to remove the excess iron. Called chelators, these drugs bind the excess iron in the body in order to then eliminate it through urine or through the intestines.
“There are a variety of chelators available, but not everyone has successful results with a single agent.”
"Some patients can't tolerate the toxicity of the side effects that result from the doses required for successful treatment, while others simply don't achieve enough of a reduction in body iron."

As a result, Dr. Lal and his colleagues wanted to determine whether or not DFX and DFO in combination couldn't provide reduced toxicity one can use lower doses of each drug while achieving highly significant reduction in whole body iron. The results of the study were overwhelmingly positive.

"We saw rapid improvement in overall body iron in heavily iron overloaded patients, who are often in the group that are the most difficult to treat," says Dr. Lal.
"By modulating the doses of the two drugs, we were able to achieve very large reductions in whole body iron. This is important, because this is a group of patients that is really vulnerable to complications of iron overload, and we want to be able to treat quickly and effectively."

Not only that, but there were no significant side effects in any of the patients. In addition, there were significant decreases in cardiac iron accumulation. The results show that DFO/DFX combination achieves comprehensive control of toxic iron species in the blood, better than achieved with previous chelation regimens.

Additional studies are required to compare the efficacy of the drug combination with a single drug treatment to confirm that DFX/DFO achieves quicker and/or larger reductions in whole body iron. Dr. Lal and his colleagues suspect that DFO/DFX will also be useful for patients unable to tolerate standard doses of single drugs, since the side effects will be significantly reduced owing to the ability to reduce the individual doses.

In the mean time however, the safety and efficacy demonstrated in the current study means that DFX/DFO can be offered to patients who either fail to achieve significant enough reductions in whole body iron on traditional treatments, or who can't tolerate the toxicities of traditional treatments.

“We have shown for the first time that, under close monitoring, DFX/DFO has an excellent safety profile while achieving significant reductions in whole body iron, especially in patients suffering from the highest levels of iron accumulation.”

"We can now offer one more option when conventional therapy fails in these patients who have so few avenues of treatment open to them," says Dr. Lal.


Friday, December 28, 2012 2:36 PM

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