David Vossler, MD: Treating Generalized Tonic-Clonic Seizures

“The problem with these genetic generalized onset epilepsies and the seizures they cause is that they’re heterogeneous. There are probably hundreds of genes that cause these, and so it’s difficult to find drugs that work for all patients.”

The treatment paradigm for patients who experience genetic generalized tonic-clonic seizures (previously known as primary generalized tonic-clonic seizures) is full of challenges. As David Vossler, MD, medical director, The Neuroscience Institute, UW Medicine Valley Medical Center, pointed out, the genetic roots of these epilepsies can be vast and varying, making therapeutic development in the fashion of one-size-fits-all essentially impossible. Additionally, up to one-third of these patients will have disease that is refractory to treatment.

This has led to a large gap in treatment. Recently, however, UCB announced that lacosamide (Vimpat) met its primary and secondary end points in a phase 3 study (NCT02408523), in which it significantly lowered the risk of patients experiencing a second primary generalized tonic-clonic seizure during a 24-week treatment period. These data suggest that the therapy might be a candidate to help fill that gap.

All told, 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).

To find out more about the therapy, the treatment landscape for these seizures, and whether or not lacosamide might offer patients and physicians an opportunity to meet an unmet need in care as UCB continues seeking an expanded indication, NeurologyLive spoke with Vossler, an author on the study, and Mike Davis, the head of US Neurology at UCB.

REFERENCE
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