XP19986 Monotherapy Generally Well Tolerated and Effective in Reducing Heartburn in GERD Subjects Previously Treated with Proton Pump Inhibitors
SANTA CLARA, Calif.--(BUSINESS WIRE)--Dec. 2, 2008--XenoPort, Inc. (Nasdaq:XNPT) announced today top-line results from a
Phase 2 clinical trial that examined the ability of XP19986 (arbaclofen
placarbil) extended-release tablets to reduce symptoms experienced
by subjects with gastroesophageal reflux disease, or GERD. The primary
analysis comparing XP19986 to placebo did not reach statistical
significance. However, pre-defined subgroup analyses showed
statistically significant benefits of XP19986 on a number of important
parameters. XP19986 was generally well tolerated at all dose levels.
Ronald W. Barrett, Ph.D., XenoPort's chief executive officer, stated,
"While we are disappointed that statistical significance in the primary
analysis of this trial was not met, we are pleased that the subgroup
analyses showed that XP19986 monotherapy was effective in reducing
heartburn in GERD subjects who have previously experienced at least a
partial response to proton pump inhibitors (PPIs). We are particularly
encouraged by the results indicating that XP19986 appears to have
acceptable tolerability for the GERD patient population. Effective
treatment for GERD patients who remain symptomatic despite PPI therapy
represents an important unmet medical need."
The randomized, parallel-group, double-blind, placebo-controlled Phase 2
clinical trial enrolled 156 subjects at 16 sites in the United States.
Enrolled subjects had reflux symptoms occurring at least three days a
week and had either no history of taking PPIs (PPI Naive) or a history
of at least a partial symptom response to PPI therapy (PPI Experienced).
Enrolled subjects discontinued prior therapy for GERD other than rescue
antacids. During the second week of a two-week washout period, baseline
data regarding frequency and severity of GERD symptoms were recorded in
an electronic diary as they occurred. Each subject who met the entry
criteria was randomized to one of five treatment arms: placebo; three
dose levels of XP19986 (20 mg, 40 mg or 60 mg) administered once a day
in the morning; or XP19986 (30 mg) administered twice daily. PPI history
was used as a stratification criterion during randomization. The
treatment period was four weeks, which included an up-titration period.
At the end of four weeks, subjects were tapered off treatment.
The primary efficacy analysis involved the difference in the change in
total number of weekly heartburn episodes between the XP19986 dose
groups and placebo through four weeks of treatment. Change in the total
number of weekly heartburn episodes was analyzed using a repeated
measures ANCOVA model. The primary efficacy analysis compared pooled
XP19986 treatment groups (60 mg dosed once a day and 30 mg dosed twice a
day; and 60 mg and 40 mg dosed once a day) with the placebo group and
included both PPI Experienced and PPI Naive subjects. This analysis did
not reach statistical significance.
The primary ANCOVA analysis indicated that the status of a subject as
either PPI Naive or PPI Experienced had a significant impact on the
outcome of the analysis (PPI history status by treatment group
interaction term (p=0.02)). The prospective statistical analysis plan
specified separate analyses of the PPI Naive and the PPI Experienced
populations. In the PPI Experienced population, which represented 63% of
all subjects, XP19986 demonstrated a significantly greater reduction in
heartburn episodes compared to placebo for the 60 mg once-daily and the
30 mg twice-daily dosage groups using the repeated measures ANCOVA
analysis (p=0.04 for both).
A number of pre-defined secondary analyses were conducted on subjects in
the PPI Experienced population who completed four weeks of treatment.
All XP19986 dose groups showed a greater adjusted mean percent reduction
from baseline at week four in weekly heartburn episodes that was
statistically significant compared to placebo. The adjusted mean percent
change from baseline measured at week four for placebo, 20 mg, 40 mg and
60 mg dosed once daily and 30 mg of XP19986 dosed twice daily was -28%,
-75%, -65%, -68% and -79%, respectively (p<0.01 for all XP19986 dose
groups compared to placebo except for 40 mg (p=0.02); no correction for
In addition, a dose-dependent effect on the complete relief of heartburn
symptoms during the last seven days of the four-week treatment period
was observed for subjects in the PPI Experienced population (7%, 21%,
24%, 33% and 60% for placebo, 20 mg, 40 mg and 60 mg dosed once daily
and 30 mg of XP19986 dosed twice daily, respectively). The comparison of
the 30 mg twice-daily group with the placebo group was statistically
significant (p=0.03; no correction for multiple comparisons).
XP19986 was generally well tolerated at all dose levels. There were no
treatment emergent serious adverse events. Among all subjects receiving
study medication, the most common adverse events for placebo, 20 mg, 40
mg and 60 mg dosed once daily and 30 mg of XP19986 dosed twice daily
were somnolence, at rates of 3%, 3%, 12%, 16% and 13%, respectively, and
dizziness, at rates of 10%, 10%, 6%, 13% and 20%, respectively. Most
reported adverse events were mild or moderate in severity. Withdrawals
due to adverse events were 6%, 0%, 3%, 9% and 10%, respectively.
"GERD is a common digestive system disorder that develops when the
reflux of stomach contents causes troublesome symptoms and/or
complications. Conventional treatments for GERD are not effective in all
patients, and can lead to serious medical consequences in some
patients," said Nimish B. Vakil, M.D., FACG, Clinical Professor of
Medicine at the University of Wisconsin Medical School and a principal
investigator of the Phase 2 clinical trial. "This trial shows the
potential of XP19986 in reducing heartburn in GERD patients who have
previously taken PPIs. The favorable tolerability of XP19986 in this
patient population is an important finding."
Ronald W. Barrett, Ph.D., XenoPort's chief executive officer, added, "A
primary goal of this trial was to advance our understanding of factors
that may influence responsiveness to XP19986, since its mechanism of
action differs from that of acid-suppressive agents. Based on the data
we have reviewed to date, we believe we have already gained insights
that will inform the design of our next trial, which will examine
XP19986 in GERD subjects who continue to experience symptoms despite PPI
therapy. We expect to provide an update on the next steps for the GERD
development program in the first quarter of next year and to present
additional results from this trial at a future medical conference."
XP19986 (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. XP19986 is then rapidly converted by
high-capacity enzymes to the parent compound and natural substances with
favorable safety characteristics. The current sustained-release tablet
formulation of XP19986 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). A GABA(B) agonist 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 GERD
and acute back spasms
GERD is a digestive system disorder affecting approximately 25% of the
U.S. population. Normally, the lower esophageal sphincter (LES), a
muscle that is located between the stomach and esophagus, prevents the
reflux of stomach contents into the esophagus. In patients suffering
from GERD, excessive transient LES relaxations (TLESRs) or a weak LES
allow frequent passage of stomach contents into the esophagus, thereby
causing the typical symptoms of heartburn and regurgitation. While GERD
can cause discomfort and a diminished quality of life, inadequate
treatment can lead to esophageal erosion, bleeding and potentially even
cancer. Current treatment of GERD primarily involves suppression of acid
secretion through the use of antacids and prescriptions drugs such as
PPIs and H2 receptor antagonists. PPI therapy is the most efficacious
and commonly used therapy to treat GERD. According to IMS Health, IMS
Midas, over $25 billion worldwide was spent in 2007 on PPI therapeutics.
While PPI therapy improves symptoms in the majority of GERD patients, an
estimated 40% of patients on once-daily PPI therapy continue to
experience breakthrough symptoms. There are no drugs currently approved
to treat patients with PPI-refractory GERD.
Conference Call and Webcast Information
XenoPort will host a conference call at 8:30 a.m. Eastern Time today to
discuss the Phase 2 clinical trial results. 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 706-679-1417.
The reference number to enter the call is 76269111.
The replay of the conference call may be accessed after 11:30 a.m.
Eastern Time today via the Internet, at www.XenoPort.com,
or via phone at 1-800-642-1687 for domestic callers, or 706-645-9291 for
international callers. The reference number to enter the replay of the
call is 76269111. Dial-in access to the replay of the call will be
available for approximately one week, and the Internet replay of the
call will be available for approximately one month following the live
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 in partnership with Astellas Pharma Inc. and GlaxoSmithKline.
GlaxoSmithKline is in the process of resubmitting to the FDA an NDA for
this product candidate, known as Solzira(TM) in the United States,
for the treatment of 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 chord
injury, acute back spasms and Parkinson's disease.
To learn more about XenoPort, please visit the Web site at www.XenoPort.com.
This press release contains "forward-looking" statements, including,
without limitation, all statements related to our future clinical
development program for XP19986 and the timing thereof; the therapeutic
and commercial potential of XP19986; and the resubmission of the NDA for Solzira.
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 "plan," "will," "expect," "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, risks related to the uncertain results of future
clinical trials; XenoPort's ability to successfully conduct future
clinical trials for XP19986; the uncertainty of the FDA approval process
and other regulatory requirements; XenoPort's dependence on its current
and additional collaborative partners; and the uncertain therapeutic and
commercial value of its 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, 2008, filed with
the Securities and Exchange Commission on November 6, 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.
XenoPort and Transported Prodrug are trademarks of XenoPort, Inc.
Solzira is a U.S. trademark of GlaxoSmithKline.
Jackie Cossmon, 408-616-7220
Source: XenoPort, Inc.