FDA APPROVES NOVANTRONEĀ® TO TREAT PROGRESSION IN MS

October 13, 2000

Summary: The U.S. Food and Drug Administration has approved marketing of NovantroneĀ® (mitoxantrone for injection concentrate) "for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary-progressive, progressive-relapsing or worsening relapsing-remitting MS."

  • This is the first therapy approved in the U.S. for secondary-progressive MS, and also offers new treatment options for others experiencing worsening of the disease.
  • Approval of the immune-suppressing drug, given by intravenous (into the vein) infusion, was based on results from European studies demonstrating benefit in slowing progression of disability, delaying and reducing frequency of relapses, and reducing accumulation of new lesions in the brain.
  • Short-term side effects and toxicity appear manageable. However, FDA approval criteria indicate that Novantrone should only be used in those with normal heart function. After a total of about 8 to 12 doses over 2 to 3 years, no more drug should be taken because of possible cumulative cardiac toxicity.
  • Novantrone is currently available. According to Immunex sources, the annual price of Novantrone will be approximately $3,000.
  • For more information, individuals can contact their physicians, or call Immunex at 1-800-5-NOVANTRONE (1-800-566-8268). Full prescribing information also is available on the company's Web site at www.immunex.com.

Details: The U.S. Food and Drug Administration has approved the marketing of NovantroneÒ (mitoxantrone for injection concentrate, distributed by Immunex Corporation, Seattle, WA) for "for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary-progressive, progressive-relapsing or worsening relapsing-remitting MS." The drug is administered via intravenous (into the vein) infusion, once every three months. This is the first therapy approved in the U.S. for secondary-progressive MS, and also offers new treatment options for others experiencing worsening of the disease.

(Secondary-progressive MS evolves in many individuals whose disease begins with clearly defined flare-ups, or relapses, with recovery, and is characterized by progression of disability with or without occasional relapses. Progressive-relapsing disease involves progression of disability from onset, with subsequent occasional disease relapses with or without full recovery. Relapsing-remitting MS involves clearly defined disease relapses with full recovery or with residual deficit upon recovery.)

Novantrone is a potent immune-suppressing agent that was previously approved only for use in acute nonlymphocytic leukemia and for pain associated with certain forms of prostate cancer. It acts by inhibiting the proliferation (division) of cells, suppressing immune-system B cells and helper T cells, and modulating other immune cells and substances. Researchers believe that MS results when such components of the immune system attack both myelin, the fatty substance that insulates nerve fibers, and the nerve fibers themselves.

Background Studies: Investigation of Novantrone for MS began in the late 1980s with studies, supported in part by the National MS Society, in animal models suggesting the drug could improve MS-like disease. The FDA based its decision on a series of clinical studies on Novantrone conducted over the past 10 years in Europe, which demonstrated benefit in slowing progression of disability, delaying and reducing frequency of relapses, and reducing accumulation of new lesions in the brain, detected by magnetic resonance imaging.

Safety and Side Effects: Short-term safety and tolerability of Novantrone in MS appear to be manageable. Common side effects include nausea, hair loss, urinary tract infections, and menstrual disorders (in females). Novantrone can increase the risk for infection, because it decreases the number of protective white blood cells. Prior to each dose of Novantrone, blood samples should be taken to check blood counts and liver function.

The longer-term safety of Novantrone in MS, particularly its impact on cardiac (heart) function, may be problematic. Dose-related cardiac toxicity has been reported with Novantrone in cumulative doses exceeding 140 mg/m2, primarily in cancer patients. Although no clinically significant cardiac toxicity was seen in the relatively short MS trials, these studies have been only 2 years or less in duration and the cumulative dose of Novantrone has been less than 100 mg/m2.

According to criteria laid out in the FDA's approval of Novantrone for MS, the drug should only be used in those with normal cardiac function, once every three months at a dose of 12mg/m2. Cardiac monitoring is required. The lifetime cumulative dose is limited to 140 mg/m2. For most, this would mean that after about 8 to 12 doses over 2 to 3 years, no more drug should be taken because of possible cardiac toxicity.

Availability/Cost: Novantrone is available now. According to Immunex sources, the annual price of Novantrone infusions will be approximately $3,000 for the drug alone, which does not include fees associated with its administration by a health professional.

Conclusions: The approval of Novantrone offers new treatment options for people with secondary-progressive, progressive-relapsing MS, and worsening relapsing-remitting MS, although potential heart toxicity limits the dosage of drug an individual will be able to take in his or her lifetime. Further research, which is ongoing, and clinical experience will help define how Novantrone will be used in the context of other treatments available for people with MS.

Individuals interested in the use of Novantrone in MS should consult their personal physicians or contact Immunex Corporation at 1-800-5-NOVANTRONE (1-800-566-8268). Full prescribing information also is available on the company's Web site, at www.immunex.com.

-- Research Programs Department
Ā© 2000 The National Multiple Sclerosis Society