By Lisa Seachrist
WASHINGTON — Preliminary Phase III clinical trial results with Immunex Corp.'s chemotherapy agent Novantrone (mitoxantrone concentrate for injection) indicate the drug can significantly reduce the incidence of relapse and disease progression in patients with progressive multiple sclerosis (MS).
Quarterly infusions of the drug not only decreased the relapse rate, but improved neurologic function and mobility as measured by disease progression scales. In addition, magnetic resonance imaging (MRI) showed Novantrone prevented new brain lesions.
"We have a meeting in the late fall with FDA to discuss what is needed to expand the label," said Lisa Crisera, spokeswoman for Seattle-based Immunex.
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.
MS, an autoimmune disease of the central nervous system, affects more than 300,000 Americans and more than a million people worldwide. In the disease, the myelin sheath — the fatty insulation surrounding nerve fibers — is damaged, causing electrical nerve signals to be distorted and blocked. Symptoms include muscle stiffness, spasms, vision problems, incontinence and memory and speech problems.
Severity ranges from a relapsing-remitting form, characterized by episodes of disability followed by relatively normal functioning, to a relentlessly progressive disability. About half of all patients who have the relapsing-remitting form eventually develop progressive MS.
Substantial Benefit Seen In Higher-Dose Group
The Phase III study was conducted in Belgium and Germany and included 194 patients with progressive MS. It compared a 12 milligram per square meter infusion or a 5 milligram per square meter infusion of Novantrone, given once every three months for two years, to a placebo.
Preliminary results were presented at the 14th Congress of the European Community for Treatment and Research in Multiple Sclerosis, in Stockholm, Sweden, by investigators from Wyeth-Ayerst Laboratories. The data showed the 12 milligram dose provided substantial benefit to MS patients, while the 5 milligram dose was somewhat less beneficial.
The median time to first relapse, a new symptom or a worsening of an existing symptom requiring treatment with corticosteriods was not reached after 24 months of treatment with either dose of Novantrone. Patients in the placebo group had a median time to first relapse of 15 months.
For the 12 milligram dose, the annual relapse rate was 21 percent. The rate for the 5 milligram dose was 36 percent, and 60 percent for the placebo group. Patients treated with either dose of Novantrone had almost no additional brain lesions as detected by MRI, while placebo patients experienced a continual increase in lesions.
Patients on both doses of Novantrone showed improvement in neurologic functions compared to placebo patients, and experienced less deterioration of mobility.
"We see the 12 milligram per meter squared dose as the optimal dose for these patients," Crisera said.
Novantrone's side effects are well established, and include nausea during and immediately after administration, neutropenia (a decrease in white blood cells), infection and hair loss.
Crisera said that, when the company meets with the FDA later this fall, it will evaluate whether the current data is sufficient to support a supplemental application for the product or additional trials will be needed. Should more trials be required, Crisera noted that Immunex is likely to continue to study patients with progressive MS, but those studies will not contain a placebo arm.
Currently in the U.S., three treatments are approved for relapsing-remitting MS: Avonex (interferon beta-1a), produced by Cambridge, Mass.-based Biogen Inc.; Betaseron (interferon beta-1b), manufactured by Chiron Corp. of Emeryville, Calif.; and Copaxone, from Teva Pharmaceutical Industries Ltd., of Jerusalem. Chiron and its marketing partner, Berlex Laboratories Inc., of Wayne, N.J., have filed for a supplemental indication in progressive MS. Biogen is conducting studies to test Avonex for that indication.
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 Thursday at $59.50, up $3.625. *