GSK epilepsy drug delayed

The US Food and Drug Administration (FDA) has pushed back the date by which it is aiming to make a decision on the marketing application for GlaxoSmithKline's (GSK) experimental epilepsy drug ezogabine from August 30 to November 30.

Ezogabine, which GSK is developing through a partnership with the speciality pharma company Valeant Pharmaceuticals International, is a neuronal potassium channel opener intended for the adjunctive treatment of adults with partial onset seizures. The companies hope to sell the drug under the tradename Potiga.

The new target date is intended to give the FDA time to review the companies' Risk Evaluation and Mitigation Strategy (REMS) for the product, which was officially submitted on August 26. The original US marketing application was filed in late October of 2009; the FDA requested the addition of the REMS in correspondence dated August 16.

The FDA's request for a formal REMS came after its Peripheral and Central Nervous System Drugs Advisory Committee unanimously voted at an August 12 meeting that the drug was effective. At that meeting, the advisors debated the drug's safety, particularly its link to urinary retention, and eventually voted overwhelmingly that the issue could be adequately addressed through patient monitoring.

The risk management programme that GSK presented during the advisory meeting included a two-year post-marketing follow-up study to monitor side effects, specifically the urinary retention adverse event. Clinical studies submitted in the marketing application showed that 5 per cent of patients on the active drug experienced urinary retention, compared with 3 per cent of patients in the placebo group. The problem appeared to be reversible.

The Food and Drug Administration Amendments Act of 2007 gave the FDA the authority to require a REMS in cases in which a risk-management plan is deemed necessary to ensure that the benefits of a drug will outweigh its risks. REMS components generally include medication guides, patient package inserts, and a communication plan for healthcare providers.

The investigational epilepsy drug is also under review in the European Union, where the non-proprietary drug name is retigabine rather than ezogabine.

GSK and Valeant, which signed their exclusive worldwide development agreement for ezogabine in 2008, are also developing the drug for other indications, including pain. Valeant stands to receive up to 50 per cent of profits on the drug under the deal.