XenoPort, Inc. (Nasdaq: XNPT) announced today the inclusion of gabapentin enacarbil, the active ingredient in HORIZANT ® (gabapentin enacarbil) Extended-Release Tablets, as an initial therapy for chronic persistent restless legs syndrome/Willis-Ekbom disease (RLS/WED) in an updated treatment algorithm for patients with RLS/WED. The WED Foundation’s algorithm, published in the current issue of Mayo Clinic Proceedings, provides information for physicians determining treatment choices for RLS/WED based on disease severity, existing comorbidities and the long-term benefits and risks of each major class of medications. The algorithm, first published in 2004, was updated to accommodate several changes in the RLS/WED treatment landscape, including additional knowledge of treatment with nonergot dopamine agonists, increased experience with calcium channel alpha-2-delta ligands and the fact that several long-acting drugs have become available. According to the revised algorithm, either non-ergot dopamine agonists or the calcium channel alpha-2-delta ligands are recommended as initial treatment for patients with chronic persistent RLS/WED, and the choice of the initial treatment should be based on the individual clinical features of RLS/WED in a given patient. “This is the second publication of clinical guidance in two months that addresses treatment and disease management considerations for RLS/WED, indicating the urgency with which the neuroscience and broader physician communities are seeking to better treat this condition,” said Mark Buchfuhrer, M.D., Medical Director of the Southern California Restless Legs Syndrome Support Group, attending physician at Downey Regional Medical Center in Downey, Calif., and member of the WED Foundation’s Medical Advisory Board and the International RLS Study Group. “This algorithm reflects evidence-based assessments and expert opinion from practical experience, and hopefully will serve as a much needed tool for physicians treating the estimated five million moderate-to-severe RLS/WED patients nationwide.” “Gabapentin enacarbil is the only non-dopamine agonist and member of the calcium channel alpha-2-delta-ligand class that is approved by the FDA for the treatment of moderate-to-severe primary RLS. We are excited that the updated algorithm recognizes gabapentin enacarbil as an appropriate initial treatment option for patients with chronic persistent RLS/WED,” stated Ronald W. Barrett, Ph.D., chief executive officer of XenoPort, Inc. “XenoPort recognizes that many RLS/WED patients have their disease for life and is committed to understanding the long-term needs of these patients.”
About HORIZANT (gabapentin enacarbil) Extended-Release TabletsGabapentin 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 the only non-dopamine agonist and calcium channel alpha-2-delta-ligand approved by the U.S. Food and Drug Administration (FDA) for the treatment of moderate-to-severe primary RLS in adults. (HORIZANT is not interchangeable with other gabapentin products). About Restless Legs Syndrome/Willis-Ekbom Disease RLS/WED is a common disorder, occurring at least twice a week and causing at least moderate distress in approximately 2 to 3% of the population. It 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 RLS may cause exhaustion, daytime fatigue, inability to concentrate and impaired memory. 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 GabapentinHORIZANT 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 REACTIONS 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. 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 ImpairmentIn 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. For HORIZANT Prescribing Information/Medical Guide, please see the following Websites: http://www.HORIZANT.com/docs/HORIZANT_PrescribingInformation.pdf http://www.HORIZANT.com/docs/HORIZANT_MedGuide.pdf 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. XenoPort is currently commercializing HORIZANT in the United States and developing its novel fumaric acid ester product candidate, XP23829, as a potential treatment for relapsing-remitting multiple sclerosis and/or psoriasis. 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. To learn more about XenoPort, please visit the company Website at www.XenoPort.com. Forward-Looking Statements This press release contains “forward-looking” statements, including, without limitation, all statements related to HORIZANT as a potential initial treatment option for patients with chronic persistent RLS/WED, future treatment decisions involving the potential use of HORIZANT and any further development plans of XenoPort. 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,” “potential,” “should,” “will” 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 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 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 June 30, 2013, filed with the Securities and Exchange Commission on August 7, 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, Transported Prodrug and XENOPORT are trademarks of XenoPort, Inc.