XenoPort Announces Inclusion of Horizant (Gabapentin Enacarbil) in
Guidelines for Long-Term Treatment of Restless Legs Syndrome/Willis-Ekbom
SANTA CLARA, Calif. -- July 23, 2013
XenoPort, Inc. (Nasdaq: XNPT) announced today the inclusion of gabapentin
enacarbil, the active ingredient in Horizant^® (gabapentin enacarbil)
Extended-Release Tablets, as a first-line therapy in new treatment guidelines
created by the Task Force of the International Restless Legs Syndrome Study
Group (IRLSSG). The manuscript, published in the current issue of Sleep
Medicine, provides information for physicians determining treatment choices
for restless legs syndrome/Willis-Ekbom Disease (RLS/WED) based on the
long-term benefits and risks of each major class of medications. Horizant is
the only non-dopamine agonist and the only alpha-2-delta ligand approved by
the U.S. Food and Drug Administration (FDA) for the treatment of
moderate-to-severe primary restless legs syndrome in adults.
“The last few years have seen tremendous advances in our knowledge of both the
etiology of RLS/WED and its effective treatment,” stated Diego
Garcia-Borreguero, M.D., Chair, International Restless Legs Study Group and
Director, Sleep Research Institute, Madrid, Spain. “These guidelines are an
important tool for guiding physicians in the choice for pharmacotherapy of
patients requiring long-term treatment of RLS/WED symptoms.”
The guidelines state that either dopamine-receptor agonists or the
alpha-2-delta ligands, which include gabapentin enacarbil, are the first-line
treatment for patients with RLS/WED, and that the choice of the initial
treatment should be based on the individual clinical features of RLS/WED in a
given patient. The guidelines indicate that alpha-2-delta ligands should be
considered for initial treatment in patients with severe sleep disturbance
(disproportionate to other RLS/WED symptoms), comorbid insomnia or anxiety,
RLS/WED-related or comorbid pain, or a history of an impulse control disorder
(ICD) or anxiety. In addition, the guidelines recommend that patients with
clinically significant daytime symptoms should be treated with a long-acting
agent. The published guidelines are available at www.IRLSSG.org.
“We are happy to see that Horizant, the only non-dopamine agonist and the only
alpha-2-delta ligand approved by the FDA, is being recognized as an important
treatment option for patients with RLS/WED,” stated Ronald W. Barrett, Ph.D.,
chief executive officer of XenoPort, Inc. “There is growing recognition that
the dopamine agonists are not appropriate or sufficient for long-term
treatment of all RLS/WED patients. We are proud to contribute an alternative
first-line treatment to the RLS/WED community.”
About Restless Legs Syndrome
RLS/WED is a neurological condition that causes an irresistible urge to move
the legs. This urge is usually caused or accompanied by unpleasant sensations
of burning, creeping, tugging or tingling inside the patients’ legs, ranging
in severity from uncomfortable to painful. These RLS-related symptoms
typically begin or worsen during periods of rest or inactivity, particularly
when lying down or sitting, and may be temporarily relieved by movement such
as walking or massaging the legs. Symptoms often worsen at night, and
disturbed sleep is a common result of RLS. Left untreated, moderate-to-severe
primary restless legs syndrome may cause exhaustion, daytime fatigue,
inability to concentrate and impaired memory.
About Horizant (gabapentin enacarbil)
Gabapentin enacarbil is a patented molecule that was discovered and developed
by XenoPort. It utilizes XenoPort’s Transported Prodrug technology that was
designed to take advantage of high-capacity transport mechanisms in the
gastrointestinal tract to offer efficient absorption and extended exposure of
gabapentin. (Horizant is not interchangeable with other gabapentin products).
IMPORTANT SAFETY INFORMATION
Effects on Driving
Horizant may cause significant driving impairment. Patients should not drive
until they have enough experience on Horizant to know if it impairs their
driving. Patients’ ability to assess their driving competence and degree of
somnolence caused by Horizant can be imperfect.
Somnolence/Sedation and Dizziness
Horizant causes somnolence/sedation and dizziness. Patients should not drive
or operate other complex machinery until they have enough experience on
Horizant to know if it impairs their ability to perform these tasks.
Lack of Interchangeability With Gabapentin
Horizant is not interchangeable with other gabapentin products because of
differing pharmacokinetic profiles. The same dose of Horizant results in
different plasma concentrations of gabapentin relative to other gabapentin
products. The safety and effectiveness of Horizant in patients with epilepsy
have not been studied.
Suicidal Behavior and Ideation
Horizant is a prodrug of gabapentin, an antiepileptic drug (AED). AEDs
increase the risk of suicidal thoughts or behavior in patients taking these
drugs for any indication. As a prodrug of gabapentin, Horizant also increases
this risk. Patients treated with any AED for any indication should be
monitored for new or worsening depression, suicidal thoughts or behavior,
and/or any unusual changes in mood or behavior. Anyone considering prescribing
Horizant must balance the risk of suicidal thoughts or behavior with the risk
of untreated illness.
Patients, caregivers, and families should be informed that Horizant increases
the risk of suicidal thoughts and behavior and should be advised of the need
to be alert for new or worsening signs of and symptoms of depression, any
unusual changes in mood or behavior, or the emergence of suicidal thoughts,
behavior, or thoughts of self-harm. Behaviors of concern should be reported
immediately to healthcare providers.
Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as
multiorgan hypersensitivity, has been reported in patients taking
antiepileptic drugs, including gabapentin. Horizant is a prodrug of
gabapentin. Some of these events have been fatal or life-threatening. DRESS
typically, although not exclusively, presents with fever, rash, and/or
lymphadenopathy, in association with other organ system involvement, such as
hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis
sometimes resembling an acute viral infection. Eosinophilia is often present.
Because this disorder is variable in its expression, other organ systems not
noted here may be involved.
It is important to note that early manifestations of hypersensitivity, such as
fever or lymphadenopathy, may be present even though rash is not evident. If
such signs or symptoms are present, the patient should be evaluated
immediately. Horizant should be discontinued if an alternative etiology for
the signs or symptoms cannot be established.
Discontinuation of Horizant
When discontinuing Horizant, patients with RLS receiving 600 mg or less once
daily can discontinue the drug without tapering. If the recommended dose is
exceeded, the dose should be reduced to 600 mg daily for 1 week prior to
discontinuation to minimize the potential of withdrawal seizure.
In an oral carcinogenicity study, gabapentin enacarbil increased the incidence
of pancreatic acinar cell adenoma and carcinoma in male and female rats. The
clinical significance of this finding is unknown.
The most common adverse reactions for patients with RLS receiving Horizant 600
mg, 1,200 mg, and placebo, respectively, were somnolence/sedation (20%, 27%,
and 6%), dizziness (13%, 22%, and 4%), headache (12%, 15%, and 11%), nausea
(6%, 7%, and 5%), and fatigue (6%, 7%, and 4%). A daily dose of 1,200 mg
provided no additional benefit compared with the 600-mg dose, but caused an
increase in adverse reactions.
Gabapentin enacarbil is released faster from Horizant Extended-Release tablets
in the presence of alcohol. Consumption of alcohol is not recommended when
taking Horizant. Horizant taken in conjunction with morphine causes increased
somnolence/sedation, dizziness, and nausea.
USE IN SPECIAL POPULATIONS
Pregnancy and Lactation
Based on animal data, Horizant may cause fetal harm. There are no adequate and
well-controlled studies of Horizant in pregnant women. Horizant should be used
during pregnancy only if potential benefit justifies potential risk to fetus.
Horizant is converted to gabapentin, which is secreted into human milk.
Discontinue nursing or discontinue Horizant, taking into account the
importance of Horizant to the mother, due to potential for adverse reactions
in nursing infants.
In patients with RLS who have compromised renal function, Horizant should be
dosed based upon creatinine clearance (CrCl): 30 to 59 mL/min, start with 300
mg per day and increase to 600 mg as needed; 15 to 29 mL/min, use 300 mg per
day; <15 mL/min, use 300 mg every other day. Horizant is not recommended for
use in patients receiving hemodialysis.
XenoPort, Inc. is a biopharmaceutical company focused on developing and
commercializing a portfolio of internally discovered product candidates for
the potential treatment of neurological disorders. We are currently
commercializing Horizant, our first approved product, and developing our novel
fumaric acid ester product candidate, XP23829, as a potential treatment for
relapsing-remitting multiple sclerosis and/or psoriasis. Horizant is being
marketed by XenoPort in the United States. Regnite® (gabapentin enacarbil)
Extended-Release Tablets is being marketed in Japan by Astellas Pharma Inc.
XenoPort's pipeline of product candidates also includes potential treatments
for patients with spasticity related to spinal cord injury and Parkinson's
This press release contains “forward-looking” statements, including, without
limitation, all statements related to Horizant as a potential treatment for
patients with RLS and future treatment decisions involving the potential use
of Horizant. 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 “may,” “should” 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,
XenoPort’s lack of commercialization experience and its ability to
successfully market and sell Horizant, including its ability to obtain
uninterrupted drug supply and appropriate pricing and reimbursement for
Horizant in an increasingly challenging environment; XenoPort’s ability to
comply with applicable regulatory guidelines and requirements with respect to
the marketing and manufacturing of Horizant or with Horizant post-marketing
commitments or requirements mandated by the U.S. Food and Drug Administration
(FDA); and the uncertain therapeutic and commercial value of XenoPort’s
product candidates. 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, 2013, filed with the Securities and Exchange
Commission on April 24, 2013. 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.
Horizant, Regnite and XENOPORT are registered trademarks of XenoPort, Inc.
Jackie Cossmon, 408-616-7220
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