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Drug Firms Target Arthritis Treatment


By the end of 1998, Jeanne Harrison thought she had lost a 20-year battle with rheumatoid arthritis. Her wrists had fused and her right elbow had locked at a 45-degree angle. She couldn't dress without help from her husband.

The medication she took to slow the disease, a powerful chemotherapy drug called methotrexate, left her nauseated and tired. It was painful to walk and to hug her two children.

Then she started taking a drug called Enbrel and everything changed. She can straighten her elbow and dress herself, and she no longer is fatigued. The pain in her joints is gone.

Three weeks ago, she enrolled in a jazz dance class near her home in Westlake Village. "This medication has truly been a miracle drug for me," said Harrison, 48.

But Enbrel is no magic bullet. It does not work for everyone and it is not a cure. To keep their disease in check, patients may have to take the drug for the rest of their lives at a cost of $12,000 a year. People who take the drug face an increased risk of infection, and the effects of long-term use aren't known.

For those reasons, doctors tend to prescribe Enbrel for patients who have not been helped by standard therapies. Still, the drug represents a breakthrough for patients and drug makers.

Enbrel is among an emerging class of drugs that attack rheumatoid arthritis on a molecular level. These drugs target specific proteins that direct the assault on cartilage and bone. The new "targeted" drugs appear to work in other chronic disorders that affect more than 8 million Americans, in addition to the 2.1 million people with rheumatoid arthritis.

That makes the business of rheumatoid arthritis treatment tempting to drug makers. Enbrel's huge sales potential prompted Amgen Inc. to pay $16 billion for Immunex Corp., which developed the drug. The deal, announced in December, is expected to close this summer.

Amgen predicts that Enbrel's annual sales will more than quadruple to $3 billion by 2005, driven in part by new uses for the drug. The Food and Drug Administration has approved its use in psoriatic arthritis. Immunex has been studying the drug as a treatment for psoriasis and ankylosing spondylitis, an arthritic condition that causes the vertebrae to fuse.

Amgen's immediate rival will be Centocor, the Johnson & Johnson unit that markets Remicade, a drug similar to Enbrel. The Centocor drug is approved as a short-term treatment for Crohn's disease, a chronic bowel inflammation that affects nearly 500,000 people in the U.S. It also is approved to treat rheumatoid arthritis, and Centocor is studying it as a treatment for ankylosing spondylitis.

But a broader competition is underway among drug companies racing to develop second-generation medications. The result for patients may be drugs that not only are better but also cheaper. Scios Inc. is testing a drug in clinical trials that it believes will be as good as Enbrel but with fewer side effects. The Scios drug, Scio-469, is cheaper to make than Enbrel and could cost 50% less.

"Enbrel is a good drug, but we can avoid the side effects at a significantly lower price," Scios Chief Executive Richard Brewer said at a recent investment conference. "I think we will take the market."

With at least a dozen drugs in various stages of testing, it is too soon to say how the category will shake out. It is a safe bet that some experimental medications won't make it out of the laboratory.

Still, industry executives say there is plenty of room for those therapies that manage to reach the marketplace. Less than 6% of rheumatoid arthritis patients use the targeted drugs, which, besides Enbrel and Remicade, include Kineret, an Amgen medication approved in November.

An aging population will further expand the opportunity for drug makers. Decision Resources, a market research firm, said the number of Americans with rheumatoid arthritis will increase by 19% this decade, to 2.8 million. The disease chiefly strikes people between ages 40 and 60 and affects twice as many women as men.

In rheumatoid arthritis, the body's immune system attacks the tissues that line and cushion the joints, eventually causing the cartilage, bone and ligaments around the joints to erode. It also can inflame the membranes around the lung and the sac around the heart. The cause of the disease isn't known.

Relief From Pain Worth the Risks

The new medicines target proteins that orchestrate the immune assault on joint tissue, thereby preventing further damage and reducing inflammation. One protein, tumor necrosis factor--or TNF--comes into play early, sending signals to cells in the immune system like a molecular Paul Revere.

Interleukin-1, a protein produced by cells in the connective tissue, similarly rallies cells.

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