FDA advisory committee votes in favor of investigational anti-epileptic drug ezogabine

GlaxoSmithKline (NYSE: GSK) and Valeant Pharmaceuticals International (NYSE: VRX) announced today that a U.S. Food and Drug Administration (FDA) advisory committee voted unanimously that clinical studies had provided substantial evidence of the effectiveness of ezogabine as adjunctive treatment for adults with partial-onset seizures.

After a review of the safety data, including urinary retention, infection and kidney stones, the majority of Committee members voted that urinary retention could be mitigated by patient monitoring and discussed how this could be addressed. The Committee also voted unanimously that monitoring should not be instituted for infection and kidney stones.  

"We are encouraged by the Advisory Committee's assessment of the efficacy and safety of ezogabine and await a decision by the FDA," said Atul Pande, MD, senior vice president, Neurosciences Medicines Development Center, North America Pharmaceuticals, GlaxoSmithKline. "For appropriate patients, we believe ezogabine could offer an important adjunctive treatment option for partial-onset seizures that are not well-controlled."

The Peripheral and Central Nervous System Drugs Advisory Committee reviewed efficacy data from three pivotal studies of ezogabine and an integrated safety data base including all patients who had at least one dose of ezogabine. Overall, ezogabine, as adjunctive therapy at a daily dose of 600, 900 or 1200 mg, reduced the median number of partial-onset seizures in adults with epilepsy not adequately controlled on one to three concomitant anti-epileptic drugs compared to placebo (standard therapy).

"We are pleased with the Advisory Committee's evaluation of ezogabine," said Susan Hall, PhD, Head of Neurology Research and Development at Valeant. "There is a significant need for additional anti-epileptic drugs because approximately one-third of patients with epilepsy continue to experience seizures despite treatment."

The FDA specifically asked the Committee to comment on risks associated with urinary retention. In the pivotal trials, urinary retention occurred at a rate of 0.9 percent in patients receiving ezogabine compared to 0.5 percent on placebo. In all studies of patients with partial-onset seizures, including open-label studies, five patients required catheterization (four on ezogabine and one on placebo).  The Committee recommended that patient monitoring for these events would be appropriate, with special attention given to specific groups that may be predisposed to urinary retention.

In the pivotal trials, the most frequently reported adverse events with the use of ezogabine 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 ezogabine compared to 12 percent on placebo.

The FDA does not have to follow the advice of the Advisory Committee, though it usually does.  The Prescription Drug User Fee Act goal date for the FDA to complete its review of the ezogabine application is August 30, 2010. The product, known as retigabine outside the U.S., also is under review by the European Medicines Agency.

SOURCE GlaxoSmithKline