By Lisa Seachrist

Washington Editor

A study of early treatment with high-dose Rebif, a recombinant interferon beta-1a produced by Ares-Serono International S.A., showed the drug delays the progression of multiple sclerosis (MS) in patients suffering from relapsing-remitting disease.

The Geneva, Switzerland-based company presented long-term data from a study of 560 patients receiving four years of Rebif therapy at a late-breaking news session Monday at the 52nd annual meeting of the American Academy of Neurology in San Diego. The four-year data indicate the higher dose is superior to the lower dose.

The company has already submitted the information to European regulatory authorities in order to change the drug's labeling information to recommend the higher dose. The company will submit the information to FDA shortly as part of an effort to get the drug approved in the U.S.

"I think this data is going to confirm the high dose is better than the low dose," said Hisham Samra, chief medical and regulatory officer for Ares-Serono. "It has raised our spirits very much that the four-year data is confirmatory. Delaying the disability caused by disease is what we believe is the advantage of our dosage."

Rebif, a subcutaneous injection, is approved in 50 countries, but is barred by provisions in the Orphan Drug Act from entering the U.S. marketplace. However, additional provisions in the law permit the FDA to approve therapies designed to treat orphan diseases if those therapies offer improved efficacy or safety over the protected therapy.

The agency barred Rebif from entering the market in March 1999 because the drug didn't offer clinical superiority to override orphan status held by existing MS drugs, most notably Biogen Inc.'s Avonex, a weekly intramuscular injection of interferon beta-1a. Cambridge, Mass.-based Biogen's exclusivity for Avonex under the Orphan Drug Act expires in May 2003. (See BioWorld Today, March 3, 1999, p.1.)

The data Ares Serono presented Monday are the long-term follow-up results from the PRISMS study (Prevention of Relapses and Disability by Interferon beta, Subcutaneously in Multiple Sclerosis). The two-year data from that study were used to support the approval of the drug in other countries. The study included 560 patients receiving either 22 micrograms of Rebif or 44 micrograms of Rebif three times a week. After two years of testing, the company proved the drug significantly reduced the number and severity of relapses, but failed to show a statistically significant difference between the two dosage groups. The four-year data show the higher dose is more effective at delaying the disability associated with the disease and the burden of disease as seen by magnetic resonance imaging.

"The dilemma for FDA is whether to delay access to this drug in light of this data," Samra said.

In order to prove Rebif offers a clinical benefit over Avonex, Ares-Serono has launched a head-to-head study between the two drugs. Samra said half of the necessary patients have been enrolled in the study to date, and he expects the agency will want to see data from the head-to-head study before agreeing to allow Rebif on the market. (See BioWorld Today, October 6, 1999, p. 1.)

In addition to Avonex, Betaseron (interferon beta-1b), a product of Chiron Corp., of Emeryville, Calif., and Berlex Laboratories Inc., a U.S. subsidiary of Berlin-based Schering AG, has Orphan Drug exclusivity protection.

Despite the encouraging data from the long-term data, Viren Mehta, founder and managing member of Mehta Partners LLC in New York, said it was far too soon to know whether Ares-Serono will be able to differentiate Rebif from Avonex.

"Prudence would suggest we should not count on it," Mehta said. "The company will be continuing to try to break through as much as possible. It is difficult to know what will happen and when it will happen."