LACOSAMIDE EFFICACY IS INDEPENDENT OF CONCOMITANT AED(S) TREATMENT [P07.121]

William Rosenfeld, Chesterfield, MO; G. David Rudd, David Hebert, Pamela Doty, Research Triangle Park, NC

Lacosamide is a new antiepileptic drug (AED) that was recently approved by the US Food and Drug Administration for the treatment of partial-onset seizures. In this poster, Rosenfeld et al demonstrated that lacosamide is a consistently effective adjunctive therapy when used in combination with a variety of concomitant AEDs.

Lacosamide is thought to improve seizure control by 2 novel mechanisms of action.^1,2 It reduces neuronal transmission within the central nervous system by selectively enhancing the slow inactivation of voltage-gated sodium channels. Lacosamide may also prevent the formation of inappropriate neuronal connections by binding to the collapsin response mediator protein-2, a modulator of axon development. In randomized, double-blind, placebo-controlled clinical trials of adult patients with uncontrolled partial-onset seizures with or without secondary generalization, the addition of lacosamide to other AEDs produced significantly greater reduction in seizure frequency than placebo.^3-5

In this analysis, data were pooled from more than 1300 patients with partial-onset seizures with or without secondary generalization who were enrolled in 3 randomized, placebo-controlled, double-blind phase II or phase III clinical trials. All 3 trials included patients who had uncontrolled seizures for at least 2 years and who had previously been treated with at least 2 AEDs. The patients were on stable doses of 1 to 3 AEDs at baseline, and were randomized to adjunctive therapy with lacosamide 400 mg per day or placebo. The studies included patients who were using a variety of concomitant AEDs, including lamotrigine (33% of patients), carbamazepine (33%), levetiracetam (30%), valproate (23%), topiramate (23%), oxcarbazepine (17%), phenytoin (14%), phenobarbital (8%), and zonisamide (7%); 83% of the patients were using 2 or more AEDs. The pooled analysis from the 3 clinical trials demonstrated that during the first 4 weeks of treatment, seizure frequency decreased by a mean of 36.8% from baseline for patients who were randomized to lacosamide versus 18.4% for patients who received placebo (P <.01). When the investigators examined the median percent reduction in seizure frequency from baseline for patients who were receiving different concomitant AEDs, they found that the magnitude of the improvement with lacosamide was quite consistent across all of the various AEDs included in the study (Table).

Table. Median Percent Reduction in Seizure Frequency from Baseline Lacosamide vs Placebo for Patients Receiving Different Concomitant AEDS

Statistical significance not reported.
AED = antiepileptic drug.

Similar outcomes were noted when the investigators compared the clinical response rates to lacosamide versus placebo for patients who were using different concomitant AEDs. For example, among patients using lamotrigine, clinical response (which was defined as a reduction in seizure frequency of at least 50% from baseline) was noted for 34% of patients treated with adjunctive lacosamide versus 19% of patients with placebo. For patients who were using carbamazepine, the clinical response rates were 37.4% versus 26.4% for lacosamide versus placebo; and for patients who were using levetiracetam, the response rates were 43.4% versus 19.4%.

In the pooled study population, 4 types of adverse events were considered potentially treatment related, were reported by at least 10% of the patients, and occurred more often in the lacosamide group than the placebo group: dizziness (29.5% vs 8.2% for lacosamide and placebo groups, respectively), headache (13.8% vs 8.8%), nausea (11.3% vs 4.4%), and diplopia (10.4% vs 1.9%). Treatment was discontinued prematurely due to adverse events by 17.2% of patients in the lacosamide group and 5.2% in the placebo group.

The results of this pooled analysis of data from 3 randomized, placebo-controlled clinical trials suggest that lacosamide is effective for the adjunctive therapy of uncontrolled epilepsy for patients using several different concomitant AEDs.

References
1. Halford JJ, Lapointe M. Clinical perspectives on lacosamide. Epilepsy Curr. 2009;9:1-9.
2. Epilepsy Foundation. UCB’s Vimpat® (Lacosamide) Approved by FDA as Add-on Therapy for Partial Onset Seizures in Adults. Available at: http://www.epilepsyfoundation.org/epilepsyusa/news/UCB_Vimpat.cfm. Accessed May 29, 2009.
3. Ben-Menachem E, Biton V, Jatuzis D, et al. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia. 2007;48:1308-1317.
4. Chung S, Sperling M, Biton V, et al. Lacosamide: efficacy and safety as oral adjunctive treatment for partial-onset seizures (SP574). Epilepsia. 2007;48(suppl 6):321.
5. Halász P, Kälviäinen R, Mazurkiewicz-Beldzińska M, et al. Adjunctive lacosamide for partial-onset seizures: Efficacy and safety results from a randomized controlled trial. Epilepsia. 2009;50:443-453.