The FDA-approved epilepsy monotherapy showed significant reductions in primary generalized tonic-clonic seizures of ≥50% and ≥75% from baseline.
David Vossler, MD
UCB announced that lacosamide (Vimpat) met its primary and secondary end points in a phase 3 study (NCT02408523), significantly lowering the risk of experiencing a second primary generalized tonic-clonic seizure (PGTCS) during a 24-week treatment period.1,2
Among a cohort of 242 patients randomized 1:1 to receive ≥1 dose of lacosamide (n = 121) or placebo (n = 121), researchers documented that treatment with lacosamide resulted in a significantly lower risk of developing a second PGTCS during the 24-week treatment (hazard ratio [HR], 0.540; P <.001) and a significantly higher rate of freedom from PGTCS during the treatment period compared with placebo (31.3% vs 17.2%; P = .011).2
“The phase 3 trial demonstrated that by adding lacosamide to existing anti-seizure medications, IGE patients with uncontrolled primary generalized tonic-clonic seizures experienced a higher rate of seizure freedom, suggesting lacosamide could be a valuable adjunctive therapy in this patient population,” David Vossler, MD, FAAN, FACNS, FAES, neurologist, University of Washington, said in a statement.1
Patients included in the study were ≥4 years of age with idiopathic generalized epilepsy (IGE) and were currently taking between 1–3 concomitant antiepileptic drugs (AEDs). Researchers used time to second PGTCS during the 24-week treatment as the primary end point of the study.
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In total, 68.1% of patients on lacosamide had ≥50% reduction from baseline in PGTCS frequency per 28 days, compared to 46.3% of those on placebo. Furthermore, reductions of ≥75% from baseline in PGTCS occurred in 57.1% and 36.4% of the lacosamide and placebo groups, respectively. Freedom from PGTCS during treatment occurred in 27.5% of patients within the lacosamide group compared to 13.2% who received placebo.
The median time to first PGTCS was 36.0 days (95% CI, 25.0–78.0) with lacosamide and 20.0 days (95% CI, 13.0–34.0) with placebo. Investigators noted that the median time to second PGTCS was 77 days for placebo group, while data for the lacosamide group was unavailable due to the fact that >50% of the patients who received the drug did not encounter a second PGTCS.
The therapy was also found to be generally safe as adjunctive treatment, with treatment-emergent adverse events (TEAEs) occurring in 96 of 121 patients (79.3%) compared to 79 of 121 patients (65.3%) on placebo. Dizziness (23.1%), somnolence (16.5%) and headache all represented the most common TEAEs seen. Notably, no patients died during the study.
A total of 51 patients in the lacosamide group and 42 patients in the placebo group had a history of absence seizures or reported absence seizures during the combined baseline or treatment period. In these patients, the 50% responder rates were 15.7%, 19.6%, and 19.6% with lacosamide and 16.7%, 14.3% and 16.7% with placebo during the titration period, first 12 weeks of the treatment period, and 24-week treatment period, respectively. Additionally, the 75% responder rates were 13.7%, 13.7% and 17.6% with lacosamide and 7.1%, 11.9% and 11.9% with placebo, respectively.
The FDA approved lacosamide as an add-on therapy for adult patients in 2008. It was later approved for a second indication as a monotherapy or adjunctive therapy in patients 4 years of age and older with partial-onset seizures in 2017. It is currently available in oral tablets, an oral solution, and intravenous injection. Lacosamide is currently not approved for PGTCS, but regulatory reviews for the drug as an adjunctive therapy for the treatment of PGTCS in patients with IGE 4 years of age and older compared to placebo are currently underway in the US, EU, Japan, and Australia, according to UCB.
"UCB remains committed to strengthening our leadership in epilepsy and to investigating new approaches and innovative solutions to deliver improved outcomes and experiences to the global epilepsy community,” Charl van Zyl, executive vice president & Head of Neurology Solutions, UCB, added in a statement. “This applies equally to our current expansive in-market epilepsy portfolio as well as to our exciting pipeline.”
1. Phase 3 data on Vimpat (lacosamide) CV in primary generalized tonic-clonic seizures published in Journal of Neurology, Neurosurgery & Psychiatry. News release. UCB. August 31, 2020. Accessed September 1, 2020. https://www.prnewswire.com/news-releases/phase-3-data-on-vimpat-lacosamide-cv-in-primary-generalized-tonic-clonic-seizures-published-in-journal-of-neurology-neurosurgery--psychiatry-301120427.html
2. Vossler DG, Knake S, O’Brien TJ, et al. Efficacy and safety of adjunctive lacosamide in the treatment of primary generalized tonic-clonic seizures: a double-blind, randomized, placebo-controlled trial. J Neurol Neurosurg Psychiatry. Published online August 18, 2020. doi: 10.1136/jnnp-2020-323524