By Randall Osborne

Ares Serono submitted a biologics license application (BLA) to the FDA for approval of Rebif, the Switzerland-based company's interferon beta-1a for relapsing-remitting and transitional multiple sclerosis (MS).

Another formulation of interferon beta-1a, Avonex, is already on the market, and Rebif — if approved — will compete with that drug, which generated $240 million last year for Biogen Inc., of Cambridge, Mass.

That's a big "if," said David Stone, an analyst with Cowen & Co., in Boston

"In the U.S., it's going to be pretty tough sledding [for Serono]," Stone concluded. "Rebif could become the third orphan drug for MS, but it's more likely the FDA will consider Serono's product the same as Biogen's, and not let it on the market."

Orphan drug status permits market exclusivity for seven years.

The other drug, Betaseron (interferon beta 1-b), is sold by Berlex Laboratories Inc., of Wayne, N.J., a subsidiary of Schering AG, of Berlin, and manufactured by Chiron Corp., of Emeryville, Calif.

Berlex, claiming that marketing approval for Avonex would violate Berlex's rights under the Orphan Drug Act, filed a lawsuit to stop the approval. A U.S. District Court judge ruled Avonex was clinically superior to Betaseron, and therefore the Orphan Drug Act did not apply. (See BioWorld Today, Oct. 11, 1996, p. 1.)

Gina Cella, spokesperson for Serono Laboratories, the Norwell, Mass.-based division of Ares-Serono, declined to contrast the drugs. Serono, of Geneva, Switzerland, last September reported positive results from its Phase III trial of Rebif. (See BioWorld Today, Oct. 2, 1997, p. 1.)

"The trial is something we're extremely proud of, the most comprehensive trial ever completed in MS," Cella said. "The data are compelling."

Rebif, Avonex Almost Same Molecule

Determining differences between drugs can be tricky, anyway, Stone said.

"If it were possible to look at a protein molecule atom by atom, you'd see differences, but those differences don't affect the action of the protein," he said.

Still, Rebif and Avonex — unlike Avonex and Betaseron — are practically the same, Stone said.

"The formulation is going to be some mixture of water and salt, and carrier proteins are sometimes used," he said, and other differences are unlikely to matter, if they exist. Stone characterized clinical results with Rebif as "somewhere between the same [as Avonex] and not quite as good."

To gain approval, Serono will have to show that it's formulation is "dramatically more convenient" by subcutaneous injection or has some other strong advantage, Stone said.

"Subcutaneous is theoretically a little easier, but having to do it more often takes that away," he added.

Cella said Serono might have a regulatory advantage in the fact that the Phase III trial of Rebif evaluated not only relapsing-remitting MS patients (the most common kind), but transitional patients — who are more disabled, and who tend to decline rapidly.

"We looked at that population specifically," Cella said.

In Europe, Serono has filed for registration of Rebif with the European Medicines Evaluation Agency and expects approval in the first half of this year. Stone said the company's approval chances seem better there.

"They'll probably be able to get on the market [in Europe] and stay on, until patent lawsuits do or don't prevent them," Stone said. "But there are both patent and orphan-product reasons why they won't get on the market here." *

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