Study Highlights Safety and Efficacy of XP13512 in Primary
Restless Legs Syndrome Patients Treated for Nine Months
SANTA CLARA, Calif. & RESEARCH TRIANGLE PARK, N.C.--(BUSINESS
WIRE)--Jan. 15, 2008--XenoPort, Inc. (Nasdaq:XNPT) and GlaxoSmithKline
(NYSE:GSK) today announced positive top-line results from a
placebo-controlled Phase 3 clinical trial designed to evaluate the
potential of XP13512 (GSK1838262) to maintain efficacy over the course
of nine months in patients with moderate-to-severe primary Restless
Legs Syndrome, or RLS. Data from this randomized withdrawal trial
showed that XP13512 was generally well-tolerated and that there was a
statistically significant difference between the percentage of
patients treated with XP13512 and placebo who met a pre-specified
relapse criteria during the randomized phase of the study.
"The results of this study strengthen our belief that XP13512 has
the potential to be a safe and effective treatment for primary RLS.
Our first placebo-controlled Phase 3 efficacy trial of XP13512, with
results announced in April 2007, demonstrated statistically
significant benefits of XP13512 in treating RLS symptoms over 12
weeks. We are encouraged by the results of this new placebo-controlled
Phase 3 clinical trial, which demonstrated that XP13512 was effective
and generally well-tolerated when administered to primary RLS patients
for nine months," said Ronald W. Barrett, Ph.D., chief executive
officer of XenoPort.
"This study is an important next step in moving toward the
submission of the NDA for XP13512, a potential new treatment for
patients with primary RLS. XenoPort and GSK are committed to
continuing research in this important area where there is still
significant unmet medical need," said Atul Pande, M.D., senior vice
president, GlaxoSmithKline Neurosciences Medicines Development Center.
This multi-center, randomized, placebo-controlled clinical trial
enrolled 327 patients diagnosed with moderate-to-severe primary RLS.
In the first phase of the trial, all patients were administered 1200
mg of XP13512, taken at approximately 5:00 p.m., for 24 weeks.
Patients were assessed to determine treatment response at the end of
this single-blind phase of the clinical trial. Responders were defined
as those patients who met three criteria: a decrease in total
International RLS (IRLS) rating scale score of six or more points
compared to baseline score, a decrease in IRLS score to less than 15
and an assessment of "much improved" or "very much improved" on the
Investigator Clinical Global Impression of Improvement (CGI-I).
Responders were required to have been stable on 1200 mg of XP13512 for
at least the last month of the 24-week treatment period.
After completing the single-blind phase, responders entered the
12-week, randomized, double-blind phase of the clinical trial.
Patients randomized to the placebo group received 600 mg of XP13512
for two weeks and then received placebo for an additional ten weeks.
Patients randomized to the XP13512 treatment group continued to
receive 1200 mg of XP13512 for the entire 12-week, double-blind
The primary endpoint of the trial was the proportion of RLS
patients who "relapsed," or had their RLS symptoms worsen, during the
12-week, double-blind treatment period. Patients were considered to
have "relapsed" if either or both of the following occurred: 1) the
patient withdrew from the clinical trial due to lack of efficacy;
and/or 2) there were two consecutive study visits in which (a) the
patient's IRLS score worsened by at least six points compared to the
IRLS score at the point of randomization; (b) the patient achieved an
IRLS score of at least 15; and (c) the patient received an assessment
of "much worse" or "very much worse" as compared to the condition of
the patient at the point of randomization using an Investigator
Clinical Global Impression of Change (CGI-C).
Clinical Trial Results
Three-hundred twenty-seven patients were enrolled in the study,
and 221 patients completed the 24-week, single-blind portion of the
clinical trial, of which 194 (88%) met the responder criteria and were
randomized to double-blind treatment.
Analysis of the primary endpoint indicated that treatment with
XP13512 resulted in a statistically significant lower proportion of
relapses compared to placebo during the double-blind treatment period
(23% placebo compared to 9% XP13512; p= 0.0158).
During the single-blind phase of the trial, 7% and 2% of
XP13512-treated patients withdrew from the clinical trial due to
adverse events or lack of efficacy, respectively. The most commonly
reported adverse events during the single-blind phase of the clinical
trial were somnolence (30%) and dizziness (22%), which were generally
mild or moderate in intensity and transient in nature.
During the double-blind phase, 0% and 3% of XP13512- and
placebo-treated patients, respectively, withdrew from the trial due to
adverse events. The incidence of somnolence and dizziness in
XP13512-treated patients during the double-blind portion of the trial
were 3% and 2%, respectively.
During the trial, there was one death that was determined to be
unrelated to XP13512 treatment. There were five other serious adverse
events, only one of which was judged as possibly related to XP13512
"We are encouraged that XP13512 treatment was associated with a
statistically significant difference from placebo in this randomized
withdrawal study, particularly in light of the stringent criteria for
relapse used in this clinical trial," added Dr. Barrett. "We are also
pleased with the tolerability profile of XP13512 in this nine-month
study. We look forward to reporting the top-line results of the final
12-week Phase 3 efficacy study of XP13512 in RLS patients later this
quarter and the expected filing of the NDA for RLS treatment in the
third quarter of this year by GSK."
Conference Call and Webcast Information
XenoPort will host a conference call at 8:30 a.m. Eastern Time
today. To access the conference call via the Internet, go to
www.XenoPort.com. To access the conference call via phone, dial
1-888-275-3514. International callers may access the call by dialing
The replay of the conference call may be accessed via the
Internet, after 11:30 a.m. Eastern Time today, at www.XenoPort.com, or
via phone at 1-800-642-1687 for domestic callers or 1-706-645-9291 for
international callers. The reference number to enter the call and the
replay of the call is 31203493.
XP13512 is a patented, new chemical entity that is designed to
improve upon the clinical utility of gabapentin by taking advantage of
high-capacity transport mechanisms in the gastrointestinal tract to
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. The syndrome is characterized by disturbing,
unpleasant and sometimes painful sensations in the legs that result in
a compelling urge to move. The discomfort is often temporarily
relieved by movement. Because symptoms typically occur at night, RLS
patients often suffer from sleep disruption. 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 XP13512 Collaborations
In December 2005, XenoPort licensed to Astellas Pharma Inc. rights
to develop and commercialize XP13512 in Japan, Korea, the Philippines,
Indonesia, Thailand and Taiwan. Astellas is currently conducting Phase
2 clinical trials of XP13512 in painful diabetic neuropathy and RLS in
Japan. In February 2007, XenoPort entered into a collaboration with
GSK for the development and commercialization of XP13512 in all
countries of the world, excluding the Astellas territory. XenoPort is
completing RLS clinical trials in the U.S. in support of the
submission of the NDA by GSK, which is expected in the third quarter
of this year. GSK is responsible for all other clinical development
and commercialization of XP13512 outside the Astellas territory. In
December 2007, GSK announced plans to initiate clinical trials of
XP13512 in 2008 for treatment of sleep disturbance in patients with
moderate-to-severe primary RLS, management of post-herpetic neuralgia
and painful diabetic neuropathy and for migraine prophylaxis.
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. XenoPort's most
advanced product candidate, XP13512, has successfully completed two
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
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
This press release contains "forward-looking" statements,
including, without limitation, all statements related to XenoPort's
and its partners' clinical development programs for XP13512 and the
timing thereof; the release of additional XP13512 clinical trial data
and the timing thereof; the potential filing of an NDA for XP13512 and
the timing thereof; the therapeutic and commercial potential of
XP13512; and GSK's future clinical trials. 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
Quarterly Report on Form 10-Q for the quarter ended September 30,
2007, filed with the Securities and Exchange Commission on November 9,
2007. 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 operating and Financial Review and Prospects in the
company's Annual Report on Form 20-F for 2006.
XenoPort is a registered U.S. trademark.
CONTACT: XenoPort Analyst/Investor Inquiries:
Jackie Cossmon, 408-616-7220
GSK Analyst/Investor Inquiries:
Frank Murdolo, 215-751-7002
Tom Curry, 215-751-5419
US Media Inquiries:
Holly Russell, 919-483-2839
SOURCE: XenoPort, Inc.