Brand Name: Novantrone
Active Ingredient: mitoxantrone
Indication: Treatment of patients with multiple sclerosis
Company Name: Immunex Corporation
Availability: FDA approval of Novantrone for multiple sclerosis on January 31, 2000. Novantrone is already marketed for the treatment patients with pain related to advanced hormone-refractory prostate cancer (when used with corticosteroids) and as part of initial combination treatment of acute nonlymphocytic leukemia in adults.
Multiple sclerosis afflicts as many as 350,000 Americans and more than a million people worldwide. Approximately half of these patients will develop an active progressive form of the disease that significantly impacts functioning. Fifteen years after diagnosis, nearly 50% of secondary progressive MS patients require walking aids, and 10% need to use a wheelchair.
The drugs that are currently available to treat multiple sclerosis are given as subcutaneous or intramuscular injections on a daily or weekly basis. Now a drug that has already been used to treat prostate cancer and leukemia patients is nearing FDA approval for MS: Novantrone (mitoxantrone for injection concentrate), which is administered every three months. Manufactured by Immunex Corporation, Novantrone was unanimously recommended for approval by the FDA Peripheral and Central Nervous System Drugs Advisory Panel on January 31. Clinical results show that Novantrone reduces the number and severity of relapses in multiple sclerosis patients and improves the presentation of brain lesions on MRI. Novantrone is given at a dose of 12 mg/m2 via short IV infusion once every three months for up to two years.
How It Works
Novantrone suppresses the activity of the T cells, B cells, and macrophages that are believed to lead the attack on the myelin sheath in the central nervous system of MS patients.
Clinical Study Results
In a two-year phase III placebo-controlled trial in MS patients – the results of which were presented by Immunex on January 31, 2000 – those who received Novantrone experienced a 65% reduction in the annual relapse rate compared to placebo, and a 64% reduction in one-point Expanded Disability Status Scale (EDSS) deterioration confirmed at 6 months. These data were corroborated by MRI data showing that the number of new brain lesions decreased in MS patients receiving Novantrone.
Previous phase II results were presented in April 1999 at the annual meeting of the American Academy of Neurology. Novantrone (12 mg/m2 and 5 mg/m2 doses) was compared to placebo in 194 patients with secondary multiple sclerosis treated for two years (via short IV infusion every three months) and followed for an additional year. Only 17% of patients in the 12 mg/m2 arm and 24% of patients in the 5 mg/m2 arm experienced a one-point EDSS deterioration, compared to 44% of patients in the placebo group. During the one-year follow-up period, more patients remained without relapse in the Novantrone groups (66% for the 12 mg/m2 group and 69% for the 5 mg/m2 group) than in the placebo group (51%). Among those who did experience relapse during this period, the mean number of relapses was 0.48 in the 12 mg/m2 group, 0.42 in the 5 mg/m2 group, and 0.74 in the placebo group.
What the Patient Should Know
Adverse effects reported by patients taking Novantrone include nausea, hair loss, urinary tract infection, menstrual disorders, upper respiratory tract infections, temporarily decreased white blood cell counts, and altered liver function tests. Functional cardiac changes including decreases in left ventricular ejection fraction and irreversible congestive heart failure can occur with Novantrone. Because of the potential for functional cardiac changes, multiple sclerosis patients receiving Novantrone should have cardiac monitoring, and treatment should be discontinued at a cumulative dose of 140 mg/m2.
Novantrone may cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.
Novantrone may impart a blue-green color to the urine for 24 hours after administration, and patients should be advised to expect this during therapy. Bluish discoloration of the sclera may also occur.