Brand Name Drug: Novantrone
Active Ingredient Drug: mitoxantrone
Indication: Reduce the number of relapses and slow down disease progression in Multiple Sclerosis (MS)
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.
Immunex submitted an NDA – New Drug Application – for Novantrone (mitoxantrone) on June 7, 1999 for a new multiple sclerosis (MS) indication, and it was granted “priority review” status on July 17, 1999. Novantrone was initially indicated for the treatment of patients with pain due to advanced hormone-refractory prostate cancer. It can also be used as a component of combination therapy for 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 (mitoxantrone) slows disease progression in MS and lessens the number of relapses through its ability to suppress the activity of T cells and B cells. These white blood cells attack the myelin that protects nerve cells, and by doing so cause the symptoms of Multiple Sclerosis.
Novantrone (mitoxantrone): Clinical Study Results
A multi-center, placebo-controlled, randomized, observer-blind study was conducted to evaluate the effects of Novantrone 12 mg/m2 and 5 mg/m2 on attacks and disease progression. Disease progression was assessed using the Expanded Disability Status Scale (EDSS). Patients were administered 12 mg/m2, 5 mg/m2, or placebo as IV infusion once every three months for two years. Follow-up studies conducted one year after treatment demonstrate the efficacy of Novantrone in reducing the number of attacks and slowing disease progression.
17% (12 mg/m2 dose) and 24% (5 mg/m2 dose) of patients experienced a deterioration measured as one point on the EDSS scale compared to 44% of patients in the placebo group. The mean number of relapses were 0.48, 0.42, and 0.74 for patients who were administered 12 mg/m2 Novantrone, 5 mg/m2 Novantrone, and placebo, respectively. Compared to 51% of the placebo group, 66% and 69% of the 12 mg/m2 Novantrone and 5 mg/m2 Novantrone groups, respectively, remained without relapse one year after treatment.
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.