New multiple sclerosis drug clears hurdle

Multiple sclerosis (MS) begins as a tragic case of mistaken identity.

 In this autoimmune disease, white blood cells, the body's roving guardians against infection, view the fatty sheath surrounding nerve fibers as a threat. The cells promptly begin to digest bits of the nerves' insulating coating. Like frayed wires, the damaged nerves short-circuit, blocking communication between brain and muscles.

 Fascinated with such processes, Ruth Arnon, Michael Sela, and Dvora Teitelbaum at the Weizmann Institute of Science in Rehovot, Israel, set out 27 years ago to create synthetic molecules capable of provoking an immune response. They ended up developing an entirely new way of treating MS -- and perhaps other autoimmune diseases as well.

 The pivotal step involved making a replica of a protein from the sheath of human nerve cells. This protein triggers an MS-like response when injected into guinea pigs, and the researchers had hoped that their replica would do the same. Instead, they found, it appears to act as a decoy, diverting the immune onslaught from nerve tissue.

"It is a new approach to the treatment of autoimmune diseases," Sela asserts. Although it will not prevent the disease, he says he thinks of the new treatment as "a synthetic 'vaccine' against MS."

 The research achieved a practical milestone on Sept. 19. A Food and Drug Administration advisory committee recommended that the agency approve one of the group's decoys, copolymer 1, as a treatment for MS. The FDA typically follows its advisory committees' advice.

 If approved, copolymer 1 would be the third drug in 3 years okayed for the treatment of MS, an incurable disease known for intermittent and progressively more severe episodes of pain and paralysis.

 Until recently, all doctors could do to slow the steady slide into paraplegia was prescribe steroids. They hoped that the anti-inflammatory drugs would hamper the immune system, forcing it to leave the nerves alone. That solution rarely worked for long.

 The two other new remedies for MS are Avonex and Betaseron, genetically engineered versions of the immune modulator interferon. Both cause unpleasant, flulike side effects.

 Copolymer 1, which patients must inject daily, appears to be free of major side effects other than a temporary inflammation at the injection site and a fleeting tightness in the chest. Like the interferons, copolymer 1 cuts the number of MS episodes by about one-third.

"Two well-controlled, double-blind studies indicate that the drug reduces the rate of relapses of MS," says Sid Gilman, chairman of the FDA advisory committee and a neurologist at the University of Michigan Medical Center in Ann Arbor.

 Made of a combination of four amino acids, copolymer 1 was developed for clinical use by Israeli chemical giant Teva Pharmaceutical Industries. The company trade-named the new drug Copaxone and designed the larger of the two trials that demonstrated its effectiveness.

 This study, carried out at 11 medical centers in the United States, involved approximately 250 patients. Half of them received the drug; the other half were given a placebo.

 Completed in 1994, the study found that people taking copolymer 1 for 35 months had 32 percent fewer relapses than those taking the placebo. People in the drug treatment group were also more likely to improve or retain the nerve function they had when entering the study, whereas those taking the placebo tended to get worse, says Teva Vice-President Carole Ben-Maimon, who presented the company's case to the FDA committee. An earlier study of just 50 patients yielded similar results, she says.

 After the committee's vote, Ben-Maimon expressed delight that the members were convinced by the firm's evidence. "We're happy for patients as well as ourselves."