By Lisa Seachrist

Washington Editor

Immunex Corp. will complete a supplemental new drug application at the end of this week for its chemotherapy agent Novantrone as a treatment for secondary progressive multiple sclerosis (MS).

The Seattle-based company will send data from a Phase III study as support for the new indication, showing that quarterly infusions of Novantrone (mitoxantrone concentrate for injection) decreased the relapse rate and improved neurologic function and mobility. The company plans to request priority review for the drug's use in secondary progressive MS, which will eventually affect approximately half of all the patients who develop MS.

"There are no other approved therapies for this stage of MS," said Lisa Crisera, communications specialist at Immunex. "And, Novantrone works by an entirely different mechanism."

Novantrone has been on the market in the U.S. since 1987 for the treatment of acute myelogenous leukemia. In 1997, the company received approval to expand the label to include the treatment of pain in late-stage prostate cancer.

Currently in the U.S., three treatments are approved for relapsing-remitting MS, the least severe form of the disease: Avonex (interferon beta-1a), produced by Cambridge, Mass.-based Biogen Inc.; Betaseron (interferon beta-1b), manufactured by Chiron Corp., of Emeryville, Calif.; and Copaxone, synthetic polypeptides comprised of four amino acids that stymie the degeneration caused by MS, from Teva Pharmaceutical Industries Ltd., of Jerusalem.

Chiron filed last year for a label expansion for Betaseron to include the more severe secondary progressive form of the disease. The FDA has yet to approve that change. Biogen is currently conducting a Phase III study to expand Avonex's label into the secondary progressive form.

Immunex conducted a Phase III study involving 194 patients with secondary progressive MS. The multicenter, placebo-controlled study compared two doses of Novantrone - 12 milligrams per meter squared and 5 milligrams per meter squared - to a placebo. The drug was administered by a short IV infusion once every three months for two years. Patients treated with the 12 milligram dose had an annual relapse rate of 21 percent. The rate for the 5 milligram dose was 36 percent, while the placebo group experienced a 60 percent relapse rate.

Three-year data from the study indicate that patients treated with Novantrone had a sustained reduction in the number of attacks and a delay in disability progression. Novantrone side effects include nausea, hair loss, upper respiratory tract infections, urinary tract infections, menstrual disorder and transient neutropenia - a reduced number of white blood cells.

MS, an autoimmune disease of the central nervous system, affects more than 300,000 Americans and more than 1 million people worldwide. Approximately 120,000 MS patients in the U.S. have the secondary progressive form of the disease.

In the disease, the myelin sheath - the fatty insulation surrounding nerve fibers - is damaged, causing electrical nerve signals to be distorted and blocked. Brain atrophy is an irreversible result of this malfunction and is associated with the symptoms of the disease, including memory loss, slurred speech and loss of muscular control.

"This drug could be very beneficial to patients who don't have any approved therapies for their disease," Crisera said.

In addition, Immunex is working on initiating a study testing Novantrone in combination with one of the other approved drugs for treatment of secondary progressive MS. The company has no plans to investigate Novantrone as a treatment for the less severe relapsing-remitting form of MS.

"We are looking at Novantrone in conjunction with [other MS drugs]," Crisera said. "Basically, we are trying to find out if combination therapy might be the future for MS therapy, especially in hard-to-treat cases."

Immunex acquired Novantrone from American Cyanamid Co., of Wayne, N.J., which purchased a majority interest in Immunex in 1993. American Home Products Corp. (AHP), of Madison, N.J., the parent company of Wyeth-Ayerst, bought Cyanamid in 1994. Immunex sells Novantrone in the U.S. and is responsible for any FDA regulatory filings. AHP, through Wyeth-Ayerst, sells the drug in Europe and will file for approval in Europe.

Immunex's stock (NASDAQ: IMNX) closed Wednesday at $127.75, up $5.125 a share.