December 10, 2002

Dec. 10, 2002 (Philadelphia) — Severely anemic people suffering iron overload from frequent blood transfusions may someday be able to clear iron build-up with a daily pill instead of lengthy infusions of deferoxamine mesylate (Desferal).

The new oral chelator, a compound known as ICL670, is headed for phase III trials with thalessemia and sickle cell anemia patients. It reduced iron by as much as 2.2 mg/g of liver in a randomized, open-label study conducted in Italy with 71 people suffering from thalessemia, a rare inherited form of anemia. A control group of patients receiving deferoxamine had an iron reduction of 1.2 mg/g after nine months of treatment.

Lead investigator Antonio Piga, MD, of Turin University in Italy presented nine-month results at the American Society of Hematology (ASH) annual meeting here. Deferoxamine is effective and has low toxicity, he said, but many patients fail to comply with the therapy because the regimen is so difficult.

"The standard therapy is so demanding for the patient," he said. "The person needs every day to insert a needle under the skin and infuse [deferoxamine] slowly eight to twelve hours every night."

Researchers have screened more than 700 compounds to find a suitable alternative to deferoxamine. ICL670 is the first to have comparable benefits without major adverse effects. It comes from a new class of iron-selective synthetic chelators called bis-hydroxyphenol-triazoles.

Thalessemia patients who received ICL670 in the 12-month study received either 10 or 30 mg/kg daily doses, with better results at the higher amount. Patients in the control group were given 40 mg/kg of deferoxamine five days per week.

Liver iron concentrations were measured every three months using a noninvasive method called SQUID (Superconducting Quantum Interference Device). Only four SQUID devices exist in the world today, Dr. Piga said — two in the U.S., one in Germany, and the one in his lab in Italy.

In addition to being far easier to take than deferoxamine, the new compound was well tolerated, according to the investigators. Mild nausea, vomiting, and skin rashes were reported at higher doses, but toxicities were said to be manageable.

Iron overload is not benign. Often undiagnosed, it has been associated with a slew of chronic disorders that occur later in life. These include heart disease, diabetes, arthritis, and liver failure.

The same drug company, Novartis of East Hanover, NJ, makes deferoxamine and ICL670, which has orphan drug status in the U.S. and Europe. About 1,000 people have thalessemia in the U.S., but the disease affects about 80,000 people worldwide, according to Dr. Piga.

If phase III trial results are positive, he predicted the new drug could be ready for approval in two years.

"This particular agent, if safe and effective, represents a major clinical advance for patients with sickle cell disease," ASH president-elect Ronald Hoffman, MD, from Harvard University in Boston, Massachusetts, told journalists in a prepared statement.

ASH 44th Annual Meeting: Abstract 5. Presented Dec. 8, 2002.

Reviewed by Gary D. Vogin, MD



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