New Drug For Rare And Deadly Disease

Federal health officials have approved the first-ever treatment for Fabry's disease, a rare, inherited disorder that often kills its sufferers — mostly men — around age 50.

The treatment, Genzyme Corp.'s Fabrazyme, replaces a fat-metabolizing enzyme that Fabry's patients lack. Without that enzyme, fats build to extremely high levels inside organs, causing heart attacks and kidney failure as well as debilitating pain.

The Food and Drug Administration approved Fabrazyme under two special programs. One allows the sale of treatments for life-threatening diseases before there's complete proof they work. The other gives seven years of marketing exclusivity to the first approved therapy for disorders so rare they're classified "orphan diseases." Fabry's disease (fa-BRAY) is thought to afflict 5,000 people worldwide.

Fabrazyme is a genetically engineered version of the missing enzyme alpha-galactosidase A. In one study of 58 patients, intravenous infusions every two weeks significantly cleared fat deposits from the kidney and certain other tissues in two-thirds of recipients.

"It is a definite improvement in quality of life," said Jaime Martinez, 42, of Scotch Plains, N.J., who is participating in another Fabrazyme study.

The drug hasn't reversed his kidney damage, but Martinez no longer requires narcotics for the once-excruciating pain in his hands and feet, and for the first time in years has enough energy to play with his children each afternoon.

The hope is that by regularly lowering fat deposits, organ failure will be delayed or prevented, said FDA Commissioner Mark McClellan.

Genzyme's study to prove if Fabrazyme has that ultimate benefit won't be finished until at least next January. Fabrazyme was deemed promising enough to begin selling now, as long as Genzyme quickly provides confirmatory data.

Genzyme will begin U.S. sales in a few weeks. A spokeswoman refused to reveal the price, but in Europe, Fabrazyme costs about $180,000 a year.

Genzyme won FDA approval over a rival, Transkaryotic Therapies' Replagal. McClellan wouldn't address that drug's future. Shares in TKT fell 88 cents, more than 13 percent, to close at $5.59 Thursday on the Nasdaq Stock Market.

The question now is whether Genzyme can ever adequately prove Fabrazyme's benefit, as required by federal law. Its ongoing study compares the drug to a dummy infusion. Many participants who don't want to risk getting a placebo probably will drop out of the study once insurance coverage kicks in, expected in a few months.

Genzyme promised FDA that it will make special efforts to retain enough participants for a valid study, through such steps as switching placebo patients to Fabrazyme as soon as they show any kidney deterioration.

But FDA also plans to allow some novel statistical analyses — including comparing medical records of how patients fared before Fabrazyme ever was developed — in assessing the drug's benefit.

It's a crucial test for the biotechnology industry: How well Genzyme works with FDA in analyzing Fabrazyme could determine how easy it will be for other rare-disease treatments to win accelerated approval.

"This is a very important treatment, potentially," McClellan said. But, "I want to be very clear about this: Effective studies after approval are essential."

Fabrazyme comes with some serious side effects, including painful infusion reactions and allergic reactions. FDA cautioned that health workers should carefully monitor patients during the every-other-week infusions.