By Randall Osborne

Planning to eventually take on Biogen Inc. with its formulation of interferon beta-1a for multiple sclerosis, Switzerland-based Ares-Serono has released results from the largest-ever controlled study of the drug.

Christophe Lamps, vice president of corporate affairs and investor relations for Ares-Serono, said the Phase III double-blind, placebo-controlled trial showed the effectiveness of the company's drug, Rebif, in slowing the progress of multiple sclerosis, relieving its exacerbation and reducing its activity as shown in magnetic resonance imaging.

"It's the first study to show efficacy on all three major aspects of the disease," Lamps said. Over a two-year period, the study examined 560 patients with relapsing-remitting multiple sclerosis, the most common form. Trials for Avonex, the interferon beta-1a drug launched in May 1996 by Biogen, lasted six months, Lamps noted. Of the Rebif subjects, 205 underwent monthly scans for the first nine months.

Dosages of Rebif were higher than doses given to Avonex subjects. At 66 mcg to 132 mcg per week, they were almost twice the Avonex trial dosages. "The study shows more is better," Lamps said. The Rebif study used subjects more disabled by the disease than those in the Avonex trial, as measured by a widely accepted disability status scale.

Administration of Rebif was subcutaneous. Avonex is injected into the muscle. "Biogen showed intramuscular [injection] is more effective than subcutaneous," Lamps said. "Our results showed there's no difference." The subcutaneous injection, using pre-filled syringes, makes the drug more convenient for users, Lamps noted.

More than 1 million people suffer with multiple sclerosis, about 350,000 of them in the U.S. The disease, which affects young adults, attacks the central nervous system.

Rebif's formulation of interferon beta-1a is not the same as Avonex, said Kathryn Bloom, spokeswoman for Biogen, of Cambridge, Mass.

For the first half of this year, Biogen reported $109 million in revenues from the sale of Avonex, which was the market leader for multiple sclerosis seven months after it was approved and now holds 60 percent of the market, Bloom said.

Another multiple sclerosis drug, Betaseron, which is interferon beta-1b, was on the market three years before Avonex arrived. Betaseron is sold by Berlex Laboratories Inc., of Wayne, N.J., a subsidiary of Berlin-based Schering A.G. Biogen and Berlex are involved in a patent dispute over Avonex.

A third drug for multiple sclerosis is Jerusalem-based Teva Pharmaceutical Industries Ltd.'s Copaxone, made up of synthetic polypeptides composed of four amino acids. "You don't hear much about Copaxone," Bloom said.

Ares-Serono's trial results, released at the annual meeting of the American Neurological Association, in San Diego, "confirmed the value of interferon beta-1a, but we certainly have better results than they do," Bloom said. Rebif's results against disability were about half as good as Avonex's results, she said. Sixty-five percent of Rebif subjects, who must be injected three times per week with Rebif as compared with Avonex's once a week, reported injection site reactions. Antibody levels were much higher, Bloom said.

Gina Cella, spokeswoman for Serono Laboratories, the Norwell, Mass.-based division of Ares-Serono, said, "The data speaks for itself, and I think it does that very well."

Ares-Serono, in Basel, Switzerland, has filed for registration with the European Medicines Evaluation Agency and expects approval in the first half of next year. "Certainly, that would impact the timing" of the new drug application, yet to be filed with the FDA, Cella said. *