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 Hypersensitivity 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. Tumorigenic Potential 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.
ADVERSE REACTIONSThe 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. DRUG INTERACTIONS 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. Renal Impairment 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. About XenoPort 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 disease. Forward-Looking Statements 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.XNPT2G