NewsRx.com, October 17, 2004
Xyrem with modafinil (Provigil) approved for the treatment
of EDS
Orphan Medical, Inc., announced positive results from a phase III (b)
trial designed to evaluate the improvement of excessive daytime sleepiness
(EDS) associated with narcolepsy when Xyrem (sodium oxybate) oral solution
is used alone or with modafinil (Provigil), a wakefulness
promoting agent approved for the treatment of EDS.
The primary endpoint of the trial was EDS as measured by the objective
Maintenance of Wakefulness Test (MWT). The secondary endpoint also measured
EDS using the Epworth Sleepiness Score. The trial demonstrated that Xyrem
monotherapy is effective in the treatment of EDS associated with narcolepsy
as measured by objective response in the MWT.
The combined use of Xyrem and modafinil showed a greater response than
either agent alone. EXCEEDS (Evaluation of Xyrem to Check Efficacy in
Excessive Daytime Sleepiness) was a double-blind, placebo-controlled,
parallel group multicenter randomized study.
This data follows the June announcement of positive clinical results
from the company's SXB-15 trial which evaluated the benefits of Xyrem
in EDS associated with narcolepsy where the use of Xyrem was incremental
to the use of stimulants or wakefulness-promoting drugs. In that trial,
adding Xyrem resulted in statistically significant improvement in EDS
as measured by The Epworth sleepiness score (ESS), the Clinical Global
Impression of Change (CGIc) and the MWT.
Bill Houghton, MD, Orphan Medical chief medical and scientific officer,
said, "Together, these two trials now demonstrate that Xyrem can
be proposed as first-line therapy in narcolepsy, since Xyrem data has
been produced to show efficacy in treating the symptoms of EDS, cataplexy
and fragmented nighttime sleep."
John H. Bullion, Orphan Medical chief executive officer, stated, "The
results of EXCEEDS further support our belief that Xyrem represents the
foundation for the treatment of narcolepsy. We intend to file a Supplemental
New Drug Application (sNDA) incorporating the results of both EDS trials
with the U.S. Food and Drug Administration (FDA) by the end of the year.
The sNDA timing will position the company for an FDA decision in 2005
that could allow us to expand the use of Xyrem to all of narcolepsy."
Narcolepsy is a chronic, debilitating neurological disease characterized
by symptoms of excessive daytime sleepiness, cataplexy (sudden loss of
muscle tone) and fragmented nighttime sleep. Excessive daytime sleepiness
is experienced by all narcolepsy patients and is usually treated with
stimulants during the day to help keep patients awake. Xyrem is currently
the only approved medication for the treatment of cataplexy.
The trial was conducted in narcoleptic patients with established EDS
for which they were treated with modafinil at doses of 200-600 mg daily.
After meeting entry criteria, and following 2 weeks of blinded randomized
treatment with modafinil and Xyrem placebo, they were randomized to four
evenly distributed groups in the trial with one group receiving active
Xyrem only, another with active modafinil alone, a third group with both
active medications, and a final group receiving both Xyrem and modafinil
placebo.
As expected, the group receiving both active medications saw the greatest
mean change of 2.7 minutes from baseline while maintained in blinded fashion
on unchanged dose of modafinil. It is not yet known if the two products
are additive or synergistic in their benefit. The Xyrem, modafinil and
combined drug treatment groups were highly statistically significant compared
to the placebo group. Changes in the Epworth Sleepiness Score (ESS) were
also measured and those results further support the MWT data.
The safety profile seen in this study was consistent with other controlled
clinical trials, with a relatively uniform distribution across all groups.
The side effect of nausea occurred more often for groups receiving Xyrem
and both Xyrem and modafinil together, as did vomiting which had a markedly
lower rate of incidence.
Headache was a common symptom in all groups, including placebo, but dizziness
and tremor were more common in the group on both drugs, as was anxiety.
The incidence of sleep walking and enuresis, previously reported in our
studies as associated with Xyrem showed a very low incidence in this study
that was not significantly different between groups.
Narcolepsy is a chronic, debilitating neurological disease. Cataplexy,
a sudden loss of muscle tone, is usually triggered by strong emotions
such as laughter, anger, or surprise.
As such, patients often selectively isolate themselves from interaction
with others resulting in a dramatic effect on a patient's quality of life.
Narcolepsy afflicts approximately 100,000 to 140,000 Americans with about
50,000 to 75,000 patients receiving some form of treatment for their symptoms.
An estimated 60-90% of those with narcolepsy suffer from cataplexy. All
patients with narcolepsy suffer from excessive daytime sleepiness.
Orphan Medical acquires, develops, and markets pharmaceuticals of high
medical value for inadequately treated and uncommon CNS diseases treated
by specialist physicians.
Copyright 2004, Medical Letter on the CDC & FDA via NewsRx.com
& NewsRx.net.
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