SEATTLE, Dec. 6 Results from RESTORE 2, aplacebo-controlled, Phase III study demonstrated that the investigationalcompound retigabine significantly reduced the number of seizures in adultpatients with refractory partial-onset epilepsy when a 600 mg or 900 mg dosewas added to a patient's current anti-epileptic drug (AED) therapy. Prior toenrollment in the retigabine clinical trials, patients were experiencingseizures despite taking stable doses of up to three AEDs.
Retigabine has a different mechanism of action than currently approvedAEDs. Retigabine is a neuronal potassium channel opener, which helps controlneuronal excitability. In epilepsy patients, brain cells can become overlyexcited, disrupting normal brain activity and causing seizures.
"Approximately 30 percent of epilepsy patients are not well-controlleddespite treatment with existing anti-epileptic drugs," said Jacqueline A.French, M.D., Professor of Neurology, New York University Medical Center andan investigator in the study. "Many of the currently available AEDs regulatesodium channels or calcium channels in the brain to help reduce seizures.Given the unmet medical need, it is hoped that medications with novelmechanisms of action, like retigabine, will improve outcomes in patients withrefractory epilepsy."
The RESTORE 2 study results were presented at the 62nd Annual Meeting ofthe American Epilepsy Society in Seattle on Saturday December 6, 2008. Inaddition to the Phase III results, five other studies of retigabine werepresented at AES.
About the Clinical Trials
The Phase III program for retigabine consisted of two randomized, double-blind, placebo-controlled, multi-center, parallel-group studies that assessedthe efficacy, safety and tolerability of retigabine as an adjunctive treatmentfor adult epilepsy patients with refractory partial-onset seizures. Theprogram, called RESTORE (Retigabine Efficacy and Safety Trial for Partial-Onset Epilepsy) 1 and 2, involved approximately 120 sites in more than 17countries worldwide.
RESTORE 1 evaluated a 1200 mg daily dose of retigabine (the highest dosein the Phase III program) versus placebo, while RESTORE 2 evaluated 600 mg and900 mg daily doses of retigabine versus placebo. In these studies, retigabinedemonstrated a statistically significant reduction in seizures compared toplacebo at all three doses when added to patients' current AED therapy.Additionally, RESTORE 2 showed a dose-dependent response when the dose ofretigabine was increased from 600 mg to 900 mg daily.
Tolerability of retigabine was generally dose-dependent. The most commonside effects associated with retigabine in the RESTORE trials occurring ingreater than or equal to 10 percent of patients included dizziness,somnolence, fatigue, confusion, dysarthria (slurred speech), ataxia (loss ofmuscle coordination), urinary tract infection, blurred vision, tremor, andnausea. Urinary bladder effects, while monitored during the studies, wereuncommonly reported.
GlaxoSmithKline (NYSE: GSK) (LSE: GSK) and Valeant PharmaceuticalsInternational (NYSE: VRX) entered into an exclusive worldwide collaborationagreement for retigabine earlier this year. The companies plan to file a NewDrug Application in the United States and a Marketing AuthorizationApplication in Europe in 2009.
Epilepsy, defined by recurrent, unprovoked seizures, is a change insensation, awareness or behavior caused by an electrical disturbance in thebrain. The kind of seizure a person has depends on which part and how much ofthe brain is affected by the disturbance. Primary generalized seizures involvethe entire brain from the outset, while partial-onset seizures begin in afocal area of the cerebral cortex. In most cases, however, the cause ofepilepsy is unknown.
Epilepsy affects more than 50 million people worldwide, including3 million Americans. Approximately 30 percent of epilepsy patients are notadequately controlled with currently prescribed AEDs.
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Valeant Pharmaceuticals International is a multinational specialtypharmaceutical company that develops, manufactures and markets a broad rangeof pharmaceutical products primarily in the areas of neurology anddermatology. More information about Valeant can be found athttp://www.valeant.com.
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Valeant Pharmaceuticals forward-looking statements
This press release contains forward-looking statements, including, but notlimited to, statements regarding expectations or plans of development programfor retigabine and the potential role retigabine could play in managingepilepsy and in treating other indications, and the commercial opportunityretigabine may present for Valeant. These statements are based upon thecurrent expectations and beliefs of Valeant's management and are subject tocertain risks and uncertainties that could cause actual results to differmaterially from those described in the forward-looking statements. These risksand uncertainties include, but are not limited to, risks and uncertaintiesrelated to the clinical development of retigabine, the fact that adverseevents are not always immediately apparent even in well designed clinicaltrials, regulatory approval processes, the potential that competitors maybring to market drugs or treatments that are more effective of morecommercially attractive than retigabine, and other risks and uncertaintiesdiscussed in the company's filings with the SEC. Valeant wishes to caution thereader that these factors are among the factors that could cause actualresults to differ materially from the expectations described in the forward-looking statements. Valeant also cautions the reader that undue relianceshould not be placed on any of the forward-looking statements, which speakonly as of the date of this release. The company undertakes no obligation toupdate any of these forward-looking statements to reflect events orcircumstances after the date of this release or to reflect actual outcomes.Inquiries: GSK US Media inquiries: Robin Gaitens (919) 483 2839 Holly Russell (919) 483 2839 GSK US Analyst/ Investor inquiries: Tom Curry (215) 751 5419 Valeant Media and Investor inquiries: Laurie W. Little (949) 461 6002
SOURCE GlaxoSmithKline; Valeant Pharmaceuticals International