SANTA CLARA, Calif.--(BUSINESS WIRE)--Jun. 30, 2009--
XenoPort, Inc. (Nasdaq:XNPT) announced today positive preliminary
results from a Phase 2 clinical trial of arbaclofen placarbil
(AP), also known as XP19986, for the treatment of patients with
spasticity due to spinal cord injury (SCI). Doses of 20 and 30 mg of AP,
given twice daily (BID), demonstrated statistically significant
improvements compared to placebo for the primary endpoint of the study.
AP was well tolerated during the trial.
“Currently available medications for treating spasticity are often
limited by their short duration of action and significant central
nervous system side effects,” said David A. Stamler, M.D., XenoPort’s
chief medical officer. “The efficacy and tolerability of AP that were
observed in this trial was encouraging, and we believe that AP offers
the potential to address important medical needs for SCI patients.”
This Phase 2 clinical trial was a randomized, double-blind,
placebo-controlled, crossover study that enrolled 37 subjects at ten
sites in the United States and Canada. Subjects with SCI between C-5 and
T-12 discontinued spasticity therapy during a one-week washout period
prior to a one-week placebo run-in period, at the end of which baseline
assessments were conducted. Subjects had an Ashworth Scale score of at
least 2 in one of six assessed muscle groups (hip abductors/adductors,
knee flexors/extensors and ankle flexors/extensors) on the most affected
leg. Subjects received either AP (10, 20 or 30 mg BID) or placebo in the
first treatment segment of the two-segment crossover design. Each
treatment segment included a titration period, followed by at least one
week at the target dose, at which time efficacy assessments were
performed (day 17 of each treatment segment). Each treatment segment
also included a down-titration period, and there was a three-day washout
between treatment segments.
The primary endpoint in this study was the difference in Ashworth Scale
score during the placebo and AP treatment segments for the muscle group
with the highest Ashworth Scale score at baseline. Ashworth Scale scores
were determined by the investigator prior to dosing, and again two, four
and six hours after the morning dose. The primary analysis used a
repeated-measures analysis of variance model and included data from the
35 subjects who completed both treatment segments.
Mean maximum baseline Ashworth Scale scores were 3.2 (n=10), 3.1 (n=12)
and 3.1 (n=13) for the 10, 20 and 30 mg BID AP dose cohorts,
respectively. For the primary endpoint, the overall adjusted mean
differences between placebo and AP over the six-hour assessment period
for these cohorts were -0.17 (not significant), -0.60 (p=0.0059) and
-0.88 (p=0.0007), respectively. AP treatment was associated with
statistically significant differences from placebo at all time points in
the 20 and 30 mg BID AP dose cohorts, indicating a treatment effect over
the 12-hour dosing interval. In a secondary analysis, 20 and 30 mg BID
of AP also showed a statistically significant difference from placebo in
the average Ashworth Scale score for all six muscle groups.
AP was well tolerated at all dose levels. There were no withdrawals due
to adverse events during the trial. The most commonly reported adverse
events while on any AP dose were urinary tract infection (11% AP; 9%
placebo), pain in extremity (8% AP; 0% placebo), insomnia (8% AP, 0%
placebo) and nasopharyngitis (8% AP; 3% placebo). Side effects were
generally mild to moderate in intensity. There were no drug-related
serious adverse events.
“These results add to a growing body of evidence suggesting the efficacy
and safety of AP in multiple indications,” said Ronald W. Barrett,
Ph.D., XenoPort’s chief executive officer. “We believe AP offers the
potential for a differentiated treatment of spasticity in SCI patients.
We intend to seek guidance from regulatory authorities regarding future
trial designs and safety database requirements for a clinical program
leading to a new drug application for AP as a potential treatment of
spasticity in SCI patients and possibly other spasticity populations.”
Conference Call
XenoPort will host a conference call at 9:00 a.m. Eastern Time today. To
access the conference call via the Internet, go to www.XenoPort.com.
To access the live conference call via phone, dial 1-888-275-3514.
International callers may access the live call by dialing 1-706-679-1417.
The replay of the conference call may be accessed after 12:00 p.m.
Eastern Time today via the Internet, 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 18012057.
About AP
AP (arbaclofen placarbil) is a Transported Prodrug of R-baclofen
that is designed to engage natural nutrient transport mechanisms found
on intestinal cell membranes, thereby gaining efficient entrance into
the bloodstream. AP is then rapidly converted by high-capacity enzymes
to R-baclofen and natural substances that have well-studied, favorable
safety characteristics. The current sustained-release tablet formulation
of AP could enable convenient once- or twice-daily dosing of subjects in
future clinical trials.
R-baclofen is an agonist of the target known as gamma amino-butyric
acid(B), or GABA(B), receptor. Racemic baclofen (a mixture of R and S
isomers) has been approved for the treatment of spasticity and has been
shown in clinical studies to have efficacy in a number of other
therapeutic indications, including gastroesophageal reflux disease
(GERD) and acute back spasms.
About Spasticity
Spasticity is a debilitating condition that is associated with some
common neurological disorders, such as multiple sclerosis, stroke and
cerebral palsy, as well as spinal cord injury. Spasticity is a condition
in which certain muscles are continuously contracted, interfering with
movement or speech. According to data from Wolters Kluwer Health, Source®
Pharmaceutical Audit Suite, for the 12 months ended December 31, 2008,
there were approximately 7.0 million prescriptions written in the United
States for the two most widely prescribed drugs for the treatment of
spasticity, racemic baclofen and tizanidine.
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. XenoPort is developing its lead product
candidate, XP13512, in collaboration with Astellas Pharma Inc. and
GlaxoSmithKline. The Food and Drug Administration is currently reviewing
the new drug application for this product candidate as a potential
treatment for moderate-to-severe primary restless legs syndrome.
XenoPort’s product candidates are also being studied for the potential
treatment of GERD, migraine headaches, neuropathic pain, spasticity
related to spinal cord injury, acute back spasms and Parkinson’s disease.
To learn more about XenoPort, please visit the Web site at www.XenoPort.com.
Forward-Looking Statements
This press release contains “forward-looking” statements, including,
without limitation, all statements related to our future clinical
development program for AP and the timing thereof; the therapeutic and
commercial potential of AP; the suitability of AP as a treatment for
spasticity; and our future clinical trials and the timing thereof. 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 “believe,” “could,” “intend,” “potential,” “suggesting” 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, risks related to the uncertain results of future
clinical trials; XenoPort’s ability to successfully conduct future
clinical trials for AP; the uncertainty of the FDA approval process and
other regulatory requirements; and the uncertain therapeutic and
commercial value of AP. 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 March 31, 2009, filed with the Securities and
Exchange Commission on May 7, 2009. 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.
XenoPort and Transported Prodrug are trademarks of XenoPort, Inc.
XNPT2C
Source: XenoPort, Inc.
XenoPort, Inc.
Jackie Cossmon, 408-616-7220
ir@xenoport.com
