October 13, 2000
Summary:
The U.S. Food and Drug Administration has approved marketing of Novantrone®
(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."
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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.
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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.
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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
NovantroneŇ (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.
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