This latest FDA indication includes adjunctive therapy for those aged 4 years and older in both the CV and intravenous formulations of the UCB product.
David Vossler, MD
The FDA has approved lacosamide (Vimpat; UCB) CV for adjunctive therapy in the treatment of patients aged 4 years and older with primary generalized tonic-clonic seizures (PGTCS; now known as genetic generalized tonic-clonic seizures), as well as the injection formulation for intravenous use in children aged 4 years and older.1
The agency decision was made based on data from a phase 3 study (NCT02408523) suggesting that the adjunctive use of lacosamide resulted in a significantly lower risk—reduced by 45%—of developing a second seizure over a 24-week treatment period (hazard ratio [HR], 0.540; P = .001). As well, patients reported a significantly higher rate of freedom from PGTCS during the treatment period compared with placebo (31.3% vs 17.2%; P = .011).2
Study investigator David Vossler, MD, medical director, The Neuroscience Institute, UW Medicine Valley Medical Center, pointed out in a recent conversation with NeurologyLive that the genetic roots of these epilepsies can be vast and varying, making therapeutic development in the fashion of one-size-fits-all essentially impossible. “It’s a large group of patients, and there is a big unmet need. Approximately one-third of these patients will be refractory to medications that we have on the market, and there are very few,” he said.
These phase 3 data—and today’s approval—suggest that the therapy might be able to help fill that gap. The FDA originally approved lacosamide as an add-on therapy for adult patients in 2008, after which, in 2017, it received a second indication as a monotherapy or adjunctive therapy in patients 4 years of age and older with partial-onset seizures.
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This most recent phase 3 trial consisted of a cohort of 242 patients randomized 1:1 to receive ≥1 dose of lacosamide (n = 121) or placebo (n = 121). In total, 68.1% of patients on lacosamide experienced a ≥50% reduction from baseline in PGTCS frequency per 28 days, compared to 46.3% of those on placebo. Additionally, reductions of ≥75% from baseline in PGTCS occurred in 57.1% and 36.4% of the lacosamide and placebo groups, respectively, while freedom from PGTCS was reported in 27.5% and 13.2%, respectively.
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. Vossler et al. noted that the median time to second PGTCS was 77 days for the 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.
Lacosamide was also observed to be generally safe as adjunctive treatment, with treatment-emergent adverse events (AEs) 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 observed AEs. 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.
“These approvals underscore UCB's commitment to people living with epilepsy and our focus on finding solutions for specific unmet needs within the epilepsy community,” said Mike Davis, head, US Neurology, UCB, in a statement.1 “We are pleased that VIMPAT is now available as a treatment option for people living with primary generalized tonic-clonic seizures on their journey to seizure control.”
Davis and Vossler recently spoke with NeurologyLive about lacosamide, the treatment landscape for these seizures, and whether or not the therapy might offer patients and physicians an opportunity to meet an unmet need in care as UCB sought this expanded indication. Watch that conversation below.