GSK/Valeant's epilepsy drug Trobalt poised for EU approval
This article was originally published in Scrip
European experts have recommended that the novel anti-epileptic Trobalt (retigabine), being developed by GlaxoSmithKline and Valeant Pharmaceuticals, should win approval in its first major market, the European Union.
The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP), last week, gave a positive opinion for the drug be authorised as an adjunctive treatment of partial onset seizures with or without secondary generalisation in adults aged 18 years and above with epilepsy.
The filing was based on the RESTORE 1 and 2 trials. "The benefits with Trobalt are its ability to be effective in partial onset epilepsy as add-on therapy. In addition, there is a high medical need in the partial epilepsy patient population," said the CHMP.
RESTORE 1 and 2 were randomised, double-blind, placebo-controlled studies, which assessed the safety and efficacy of retigabine in adults who experienced four or more partial-onset seizures during a 28-day period and were refractory to other treatments. Patients had been taking 1 to 3 anti-epileptic drugs, and they could also have had vagus nerve stimulation as adjunctive treatment.
Trial participants were titrated to retigabine 600 or 900 mg per day in RESTORE 2 and to 1,200 mg per day in RESTORE 1, administered in 3 divided doses, or were given placebo TID. The multicentre study lasted 32 weeks, which included an eight-week baseline phase, a six-week titration phase, a 12-week maintenance phase, and a six-week transition phase.
Outcome measures included the percentage of responders -- patients with more than 50% of reduction in seizure frequency -- during the maintenance phase, as well as the percent change in partial seizure frequency in a 28-day period from baseline to maintenance. Patients were divided into two categories, based on seizure frequency at baseline (eight seizures or fewer/28 days and more than eight seizures/28-days).
Responder rate during maintenance was greater for retigabine versus placebo in both seizure frequency categories in RESTORE 1 (P < .001)="" and="" restore="" 2="">P < .001).="" a="" similar="" pattern="" was="" seen="" in="" median="" percent="" change="" from="" baseline="" to="" maintenance="" in="" total="" partial-seizure="" frequency/28-days.="" adverse="" events="" included="" dizziness,="" somnolence,="" headache,="" fatigue,="" and="">
Retigabine is a neuronal potassium channel agonist that acts to reduce neuron excitability and differs from other anti-epileptics, which act on sodium or calcium channels or various GABA receptors.
GSK has declined to comment on details of the product's launch until approval had been finalised.
Swissmedic, the Swiss regulatory agency gave the drug a preliminary approval in December 2010. However, the product has hit delays in the US. The FDA sent the two firms a complete response letter and failed to approve the NDA for the product in its current form for unspecified "non-clinical" reasons (scripintelligence.com, 2 December 2010).
Retigabine is known in the US as ezogabine under the brand name Potiga.
GSK licensed rights to the drug from Valeant in 2008, paying $280 million upfront, plus milestones and royalties. Both companies are jointly developing Trobalt.