Lamictal (lamotrigine) XR, GSK’s enteric-coated, slow-release formulation of the leading antiepileptic drug, is an effective, well-tolerated treatment for partial seizures, according to a study in the latest issue of Neurology. The study gives the blockbuster franchise a boost as patent protection on the immediate-release formulation wanes, although the future of the drug looks a litte uncertain after being awarded an approvable letter from US drug regulators back in September. GSK has also said it does not plan to seek approval of Lamictal XR in the European Union.
The study enrolled 243 patients, aged over 12 years old, diagnosed with partial seizures and taking one or two antiepileptic drugs. Patients received adjunctive once-daily Lamotrigine XR or placebo. The study comprised three phases: baseline; double-blind dose escalation over seven weeks; and 12-weeks double-blind maintenance treatment.
Lamotrigine XR reduced the number of seizures by 46.1% over the entire study, by 28.0% during dose escalation and by 58.0% during maintenance treatment. This compared with 24.2%, 16.3% and 26.7% respectively in the placebo arm. Furthermore, 42.2% and 24.2% of the lamotrigine XR and placebo group respectively experienced at least a 50% reduction in seizure frequency. Patients taking lamotrigine XR also reached a 50% reduction in seizure frequency more rapidly than those taking placebo. Secondarily generalized seizures showed a similar improvement with lamotrigine XR compared with placebo.
Headache (lamotrigine XR 17%; placebo 15%) and dizziness (lamotrigine XR 18%, placebo 5%) emerged as the most common adverse events. No significant difference between lamotrigine XR and placebo emerged on measures of health outcomes, such as quality of life and mood. “Once-daily adjunctive lamotrigine extended-release compared with placebo effectively reduced partial seizure frequency and was well tolerated in this double-blind study,” the authors concluded.
Patients take immediate-release lamotrigine twice-daily with concurrent enzyme-inducing anti-epileptic drugs or as monotherapy and either once- or twice-daily with valproate. However, Lamotrigine XR is suitable for once-daily dosing in epilepsy regardless of concomitant treatment.
In September, the FDA issued an approvable letter for Lamictal XR. (An approvable letter contains conditions that must be satisfied before the FDA grants final marketing approval.) GSK say they are “committed to working with the FDA to address any questions they have and evaluate the best way forward”. Sales for Lamictal immediate release reached £271 million in the second-quarter 2007. GSK says that they do not intend to file in the EU.