Gene Therapy Could Mount Challenge to Amgen Drug : Health: Analysts say the threat to Thousand Oaks biotechnology giant’s Epogen is many years away and remains highly speculative.

An experimental gene therapy that might begin human trials in about a year could one day siphon off sales of Amgen Inc.’s blockbuster Epogen drug, a genetically engineered protein used to treat patients with severe anemia.

But the potential threat to Amgen is many years away and highly speculative at that.

“People who want to lose sleep over this should set their clocks for the year 2000,” said David Stone, an analyst at the investment firm Cowen & Co. in Boston.

Amgen, the Thousand Oaks biotechnology giant, has marketed Epogen since 1989. Last year it sold $506 million worth of the drug, and sales are expected to reach $560 million this year.

Epogen is a genetically engineered copy of erythropoietin (EPO), a human protein. EPO is normally made in the kidney and stimulates red blood cell production. Kidney dialysis patients often are bedridden and suffer from chronic anemia because they aren’t producing enough EPO, a problem that is cured by regular injections of Epogen.

But Epogen is expensive. The cost of the drug averages about $4,000 to $6,000 a year.

Now scientists, led by Jeffrey Leiden of the University of Chicago, in partnership with Vical Inc., a La Jolla-based biotechnology company, say they are experimenting with a gene therapy approach to curing severe anemia in the 135,000 kidney-disease patients who now depend on Epogen. The gene therapy, which involves replacing unhealthy genes with healthy ones, is also thought to have potential for AIDS patients suffering from severe anemia.

If it works, kidney patients would no longer need Amgen’s expensive drug.

In the past three years, gene therapy has emerged as a promising but controversial potential treatment for everything from inborn genetic defects to cancer and AIDS.

In a groundbreaking experiment in 1990, two young girls suffering from a rare genetic disorder that destroys immune systems were able to lead relatively normal lives due to gene therapy treatments. There are now dozens of gene therapy experiments under way, but many obstacles and unanswered questions remain.

In concept, gene therapy is simple: A malfunctioning gene is replaced in a cell by a healthy gene.

The most common method of replacing a bad gene with a good one is to infuse into a patient’s bloodstream cells that have been genetically engineered to produce the missing protein. Many such techniques use a portion of certain viruses called retroviruses, which include some rare kinds of cancers and the virus that causes AIDS.

These retroviruses are chosen because they are good at entering cells and incorporating new genes into these cells. Scientists believe they can genetically alter the retroviruses to stop their ability to replicate, thus rendering them harmless. But some critics warn that the viruses might eventually regain the ability to reproduce or combine with others to form lethal viruses.

Leiden said that the gene therapy he and his colleagues are working on involves inserting the gene for EPO into immature muscle cells, called myoblasts. It is hoped that the myoblasts will attach themselves in the body and steadily secrete EPO into the bloodstream.

But it isn’t yet known how to regulate gene therapy so that the inserted gene will stimulate the correct amount of missing protein. If too high a level of EPO is produced, for instance, an excess of red blood cells could be created, leading to heart disease. If too few red bloods cells are produced, the treatment would be ineffective.

And it’s not yet clear whether gene therapy will be long-lasting, or if it will require repeated treatments.

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Analysts say it would be at least 2000 before an anemia gene-therapy treatment could be made commercially available because of the time needed to complete clinical trials and obtain Food and Drug Administration approval.

Kidney patients typically receive three injections of Epogen per week. “This drug has no side effects, it works every time and it’s cost-effective relative to blood transfusions,” said analyst Stone.

Daniel Vapnek, Amgen’s senior vice president for research, said the company has looked into gene therapy itself, but decided that it wasn’t worth pursuing for EPO because of the potential drawbacks and the fact that Epogen is already so effective. Vapnek believes that future gene therapy methods will be used primarily for life-threatening diseases for which adequate treatments don’t currently exist, such as cystic fibrosis or AIDS.

But Leiden said that severe anemia was chosen for the research because of the large number of patients with that health problem. Also, he said, if the gene therapy experiments are successful it could lead to treatments for other disorders caused by insufficient amounts of certain proteins in the bloodstream, such as diabetes, hemophilia and dwarfism.

While there are existing treatments for many of these diseases, Leiden said, “the problem is, they’re extremely expensive and inconvenient for the patient.”

Getting gene therapy to the point where it is cost-effective, and able to correct a disorder with a single treatment, is “exactly what we’re working on,” he said.

Leiden is now doing the gene-therapy experiments with mice. He plans to submit the data from that research to the Food and Drug Administration, and if he receives approval, human trials could begin in about a year.