EC grants marketing authorization for GSK, Valeant's Trobalt to treat epilepsy

GlaxoSmithKline (GSK) and Valeant Pharmaceuticals International, Inc. (NYSE: VRX) (TSX: VRX) announced today that the European Commission has granted marketing authorisation for Trobalt™ (retigabine) as an adjunctive (add-on) treatment of partial onset seizures (a form of epilepsy where a seizure begins in a specific area in one side of the brain), with or without secondary generalisation in adults aged 18 years and above with epilepsy.

"The European authorisation of retigabine is very welcome as it will provide neurologists within Europe with a new therapeutic option for the management of appropriate patients with uncontrolled partial onset seizures," said Dr. Tony Hoos, Senior Vice President, European Medical Affairs, GSK.

This European licence was supported by the results of the pivotal phase III studies RESTORE 1 and 2, and Study 205, a phase IIb study. The results of these three studies showed that more patients with partial onset seizures saw a reduction of 50% or more in seizure frequency compared to placebo, when a 600mg, 900mg or 1200mg dose of retigabine was added to their current anti-epileptic drug (AED) therapy.

In controlled clinical studies with retigabine, urinary retention occurred at a rate of 0.9 percent in patients receiving the drug compared to 0.5 percent on placebo. Across the phase II/III safety population there were four (0.3%) serious adverse events of urinary retention, three of which were known to have resulted in withdrawal. The EU prescribing information therefore recommends that retigabine is used with caution in patients at risk of urinary retention.

Retigabine also caused a prolongation of the QT interval (electrical activity of the heart) when used at the highest dose in healthy volunteers in a thorough QT study. As a precaution, the EU prescribing information recommends that an ECG is recorded before the initiation of retigabine in patients who are taking any medication that may interfere with QT intervals or who may have congestive heart failure, ventricular hypertrophy, hypokalaemia or hypomagnesaemia and in patients initiating treatment who are 65 years of age and above.

In the pivotal trials, the most frequently reported adverse events with the use of retigabine in combination with other AEDs (occurring in at least 5 percent of subjects and at least twice the placebo rate) were dizziness (23 percent), fatigue (15 percent), confusion (9 percent), vertigo (8 percent), tremor (8 percent), abnormal coordination (7 percent), double vision (7 percent), disturbance in attention (6 percent), memory impairment (6 percent), and visual blurring (5 percent). In addition, somnolence occurred in 22 percent of patients on retigabine compared to 12 percent on placebo.

Retigabine, referred to as ezogabine in the U.S. and Canada, is being jointly developed by GSK and Valeant.

"We are very pleased to have reached such an important milestone in the development of retigabine," said Susan Hall, Ph.D., Head of Research and Development at Valeant.  "There is a significant need for new AEDs and retigabine could potentially play an important role in the management of partial onset seizures in appropriate patients."

This European authorisation represents the first licence for retigabine. Preliminary authorisation was granted by the Swiss Agency for Therapeutics Products in December 2010.  Applications for marketing authorisation have been submitted in six countries in addition to the EU.  In December 2010, GSK and Valeant announced receipt of a Complete Response letter from the U.S. Food and Drug Administration (FDA) for the New Drug Application for ezogabine, the U.S. generic name for retigabine, and are working to submit a response to the FDA as soon as possible in 2011.