Data Presented at the American Academy of Neurology Show XP13512/GSK1838262 Significantly...

Data Presented at the American Academy of Neurology Show XP13512/GSK1838262
Significantly Improved Symptoms of Moderate-to-Severe Primary Restless Legs
Syndrome
Additional Data Demonstrate Predictable, Extended Exposure with Sustained-
Release Formulation

CHICAGO, April 17 /PRNewswire/ -- Data from the first pivotal study of
XP13512/GSK1838262, a sustained-release investigational compound to treat
Restless Legs Syndrome (RLS), showed that it significantly improved the
symptoms of moderate-to-severe primary RLS compared to placebo, and was
generally well-tolerated when administered once-daily for 12 weeks.
Data from the PIVOT RLS I (Patient Improvement in Vital Outcomes following
Treatment for RLS) clinical trial, formerly designated as study XP052, were
presented today at the 60th annual meeting of the American Academy of
Neurology (AAN). The investigational compound is being developed by XenoPort
(Nasdaq: XNPT) and GlaxoSmithKline (NYSE: GSK).
"This novel compound is the first non-dopaminergic agent to demonstrate
efficacy in treating the symptoms of RLS in large controlled clinical trials,"
said Clete Kushida, M.D., director of the Stanford Center for Human Sleep
Research and a clinical investigator in the PIVOT RLS I clinical trial.
Additional data presented at the meeting compared the pharmacokinetic
profiles of an immediate-release formulation of XP13512, a sustained-release
formulation of XP13512, and commercially-available gabapentin. The sustained-
release formulation of XP13512, used in the PIVOT RLS I clinical trial
presented at AAN, provided predictable and extended exposure in healthy
volunteers compared with commercially-available gabapentin.
Absorption of commercially-available gabapentin is limited to a narrow
region in the intestinal tract and can saturate at normal clinical doses.
Once saturation occurs, additional gabapentin can not be absorbed. In
addition, absorption rates can vary from patient to patient. In contrast,
studies with both the immediate-release and the sustained-release formulations
indicated that XP13512 was well-absorbed, converted rapidly to gabapentin and
provided high bioavailability (>70 percent) and dose-proportional exposure.
"XP13512 is absorbed by high-capacity nutrient transporters located
throughout the intestinal tract," said Ken Cundy, Ph.D., senior vice
president, Preclinical Development for XenoPort. "The unique absorption
mechanism of this compound overcomes the pharmacokinetic limitations of
commercially-available gabapentin and allows for sustained, dose-proportional
exposure to gabapentin."
About PIVOT RLS I (Study XP052)
PIVOT RLS I, a 12-week, multicenter, randomized, double-blind, placebo-
controlled clinical trial of XP13512 was designed to assess efficacy and
tolerability in adults with moderate-to-severe primary RLS. The study
included 220 patients randomized to receive either XP13512 1200 mg (n=112) or
placebo (n=108) once-daily at 5:00 p.m. with food. Co-primary endpoints in
the study were mean change from baseline in the International Restless Legs
Syndrome (IRLS) Scale total score and the proportion of responders (defined as
ratings of 'very much improved' or 'much improved') on the investigator-rated
Clinical Global Impression of Improvement (CGI-I) Scale at Week 12. Adverse
events, vital signs and laboratory tests were used to assess tolerability.
Study results showed that the unadjusted mean change from baseline in IRLS
Scale total score at Week 12 was significantly greater for XP13512 (-13.2)
compared to placebo (-8.8) with an adjusted mean treatment difference of -4.0,
95% CI: (-6.2, -1.9) (P=0.0003). In addition, a significantly greater
proportion of patients treated with XP13512 (76.1 percent) was rated as
responders on the CGI-I Scale compared to placebo (38.9 percent; P<0.0001).
Sleep disturbance is often associated with RLS. In this clinical trial,
patients completed the Medical Outcomes Study (MOS) Sleep Scale to assess the
impact of XP13512 treatment on sleep. At Week 12, XP13512-treated patients,
compared to placebo-treated patients, had statistically significant
improvements in sleep quantity and sleep adequacy, as well as statistically
significant reductions in sleep disturbance and daytime somnolence.
The PIVOT RLS I clinical trial used a 24-hour diary to collect the
presence and severity of RLS symptoms every 30 minutes starting at 8:00 a.m.
At the end of the study, more than half of patients treated with XP13512 were
symptom-free for the 24-hour assessment period compared to 18 percent of
placebo-treated patients.
The two most commonly reported adverse events in the study were somnolence
(27 percent, XP13512 vs. 7 percent, placebo) and dizziness (20 percent,
XP13512 vs. 5 percent, placebo), with the majority reported as mild-to-
moderate in intensity. Nine patients (8 percent) who received XP13512
withdrew from study participation due to adverse events compared to three
patients (3 percent) who received placebo. No clinically meaningful changes
in vital signs or laboratory parameters were observed.
In addition, the Epworth Sleepiness Scale (ESS), a reliable tool designed
to measure daytime drowsiness, was used to evaluate the likelihood of patients
dozing or falling asleep in common situations of daily living, such as sitting
and reading or watching TV. At Week 12, the ESS scores for patients in the
XP13512 group were lower than patients in the placebo group, indicating that
XP13512 treatment was associated with less daytime drowsiness. The findings
on the ESS scale are consistent with the reduction in daytime somnolence
associated with XP13512 treatment as assessed by the MOS Sleep scale.
About RLS
According to the National Institutes of Health, up to 12 million people in
the U.S. are afflicted with RLS across a range of severity from mild to
severe. RLS was identified in the early 1940's by neurologist Dr. Karl Ekbom,
and is characterized by a compelling urge to move the legs and by
uncomfortable and unpleasant sensations in the legs often described as
creeping-crawling, throbbing, pulling or tightening. Symptoms of RLS
generally occur at rest, such as when sitting, lying or sleeping, and are
temporarily relieved by movement. These symptoms can significantly disrupt a
patient's sleep and daily activities. People with RLS often have difficulty
falling asleep and can feel tired during the day. RLS symptoms can be
debilitating -- published data suggest that RLS can have an impact on quality
of life equivalent to, or worse than, major chronic medical disorders such as
diabetes and osteoarthritis.
About XenoPort
XenoPort, Inc. is a biopharmaceutical company focused on developing a
portfolio of internally discovered product candidates that utilize the body's
natural nutrient transport mechanisms to improve the therapeutic benefits of
existing drugs. Its development and commercialization efforts are currently
focused on potential treatments of central nervous system disorders.
XenoPort's most advanced product candidate, XP13512, has successfully
completed three pivotal trials in its Phase 3 clinical program for the
treatment of moderate-to-severe primary RLS, and has successfully completed a
Phase 2a clinical trial for the management of post-herpetic neuralgia.
XenoPort has also reported positive results from a Phase 2a clinical trial of
its second product candidate, XP19986, in patients with gastroesophageal
reflux disease. To learn more about XenoPort, please visit the web site at
www.XenoPort.com.
About GlaxoSmithKline
GlaxoSmithKline is one of the world's leading research-based
pharmaceutical and healthcare companies and is committed to improving the
quality of human life by enabling people to do more, feel better and live
longer. For more information, visit GlaxoSmithKline at www.gsk.com.
XenoPort Forward-Looking Statement
This press release contains "forward-looking" statements, including,
without limitation, all statements related to the therapeutic and commercial
potential of XP13512. Any statements contained in this press release that are
not statements of historical fact may be deemed to be forward-looking
statements. Words such as "believes", "plans", "expected", "will", "potential"
and similar expressions are intended to identify forward-looking statements.
These forward-looking statements are based upon XenoPort's current
expectations. Forward-looking statements involve risks and uncertainties.
XenoPort' s actual results and the timing of events could differ materially
from those anticipated in such forward-looking statements as a result of these
risks and uncertainties, which include, without limitation, the ability of the
company to successfully conduct the clinical trials for XP13512, and the
results thereof; the uncertainty of the FDA approval process and other
regulatory requirements; XenoPort' s dependence on its current and additional
collaborative partners; and the therapeutic and commercial value of the
company' s compounds. These and other risk factors are discussed under the
heading "Risk Factors " in XenoPort' s Annual Report on Form 10-K for the year
ended December 31, 2007, filed with the Securities and Exchange Commission on
February 22, 2008. XenoPort expressly disclaims any obligation or undertaking
to release publicly any updates or revisions to any forward-looking statements
contained herein to reflect any change in the company' s expectations with
regard thereto or any change in events, conditions or circumstances on which
any such statements are based.
GlaxoSmithKline Forward-Looking Statement
Under the safe harbor provisions of the U.S. Private Securities Litigation
Reform Act of 1995, GSK cautions investors that any forward-looking statements
or projections made by GSK, including those made in this announcement, are
subject to risks and uncertainties that may cause actual results to differ
materially from those projected. Factors that may affect GSK' s operations are
described under 'Risk Factors' in the 'Business Review' in the company' s
Annual Report on Form 20-F for 2007.
XenoPort is a registered U.S. trademark.
SOURCE GlaxoSmithKline

XenoPort Analyst/Investor, Jackie Cossmon, +1-408-616-7220, or US Media, Holly
Russell of GlaxoSmithKline, +1-919-483-2839, or Mariesa Kemble of Sam Brown
Inc., +1-608-850-4745, for GlaxoSmithKline, GSK US Analyst/Investor, Frank
Murdolo, +1-215-751-7002, or Tom Curry, +1-215-751-5419