Lacosamide Displays Positive Efficacy and Safety in Phase 2 Clinical Trial of Neonatal Seizures

A phase 2 multicenter, randomized, open-label, active comparator (AC) trial, coined SP0968 (NCT04519645), revealed positive efficacy, safety, and pharmacokinetic data for investigational lacosamide (LMC) in treating neonates with repeated electroencephalographic neonatal seizures (ENS).

Findings from the study indicated that LCM both reduced seizure burden and was well tolerated by patients. The study also found that despite the increased LCM exposure observed in neonates, their serum concentrations remained broadly consistent with adult levels at a dose of 400 mg/day in the absence of inducers.¹

Presented at the 2025 American Epilepsy Society (AES) Annual Meeting, held December 5-9, in Atlanta Georgia, the study randomized participants 1:1 to either LCM 15 mg/kg/day (5 mg/kg every 8-hours via 30-min intravenous infusions) or AC, selected and dosed according to local standard of care and treatment guidelines. The primary outcome of the study was the change in seizure burden, measured as minutes of electrographic neonatal seizures (ENS) per hour, from baseline video electroencephalography (vEEG; −2 to 0 hours before treatment) to the evaluation period vEEG (1 to 3 hours after treatment). Secondary outcomes included the incidence of treatment-emergent adverse events (TEAEs) and mean serum concentrations of LCM.

Rescue medication (RM) was permitted when needed; however, participants who received RM within 3 hours after the first dose were excluded from the primary efficacy analysis and were considered non-responders for responder outcomes. Patients who benefited from their randomized treatment were eligible to continue in an extension period of up to 28 days postnatal age.

Led by Wendy Waldman Zadeh, MD, a neurologist at Broadlawns Medical Center in Des Moines, Iowa, the study included 26 patients who received at least one dose of study treatment: 14 were assigned to LCM and 12 to the AC (mean PNA 3.7 days; 53.8% female; Safety Set [SS]). Among patients who did not receive rescue medication (RM)(LCM n=11; AC n=9), the median reduction in seizure burden from baseline to the evaluation period was 4.74 min/h (range: −0.9 to 22.0) with LCM and 2.51 min/h (range: −32.4 to 19.6) with AC. In the LCM and AC groups, 9/15 (60.0%) and 6/9 (66.7%) were responders; 9/15 (60.0%) and 4/9 (44.4%) achieved ≥80% response; and 9/14 (64.3%) and 6/8 (75.0%) were seizure-free at 24 hours, respectively.

Regarding adverse events, 9 patients (64.3%) in the LCM group experienced 21 TEAEs, 1 patient (7.1%) had 2 drug-related TEAEs, and 2 patients (14.3%) had a single serious TEAE each. In the AC group, 5 (41.7%) patients had 21 TEAEs. Furthermore, the geometric mean serum concentration of LCM was 7.003 μg/mL at 30–90 min (n = 11) and 5.949 μg/mL at 6–8 h (n = 12) after start of first infusion (Pharmacokinetic Per-Protocol Set).

Read More: Lacosamide Provides Benefit as Second-Line Treatment for Refractory Trigeminal Neuralgia

Lacosamide was previously studied in a retrospective descriptive cohort trial. Findings from that trial demonstrated that the antiepileptic agent can be a valid alternative for patients with trigeminal neuralgia (TN) who fail first-line treatments, apart from its potential previously reported use as an intravenous rescue medication.²

Data were collected on 86 patients with refractory TN who has previously tried the treatments carbamazepine or oxcarbazepine. More than half (54%) of the cohort continued on either of those therapies as a concomitant treatment, and 14% were treated with lacosamide as monotherapy.

At the conclusion of the analysis, two-thirds (66%) of patients achieved pain relief from their condition. AEs, found in 33% of the cohort, were mild in all cases. During the follow-up, 44% (n = 38) of patients suspended lacosamide treatment, with reasons that included clinical improvement (34%; n = 13), inefficacy (45%; n = 17), and intolerance (21%; n = 8). Investigators found no statistically significant differences in demographical and clinical data between responders and nonresponders, except for bilateral pain distribution, for which the 3 patients were all nonresponders.

REFERENCES
1. Moseley B, Cleveland J, Krauwinkel W, et al. Efficacy, Safety, and Pharmacokinetics of Lacosamide in NeonatesWith Seizures: Results of a Phase 2/3, Open-Label, Randomized, Active Comparator Trial . Presented at 2025 American Epilepsy Society Annual Meeting; December 5-9, Atlanta, Georgia.
2. Munoz-Vendrell A, Tena-Cucala R, Campoy S, et al. Oral lacosamide for the treatment of refractory trigeminal neuralgia: a retrospective analysis of 86 cases. Headache. Published online April 10, 2023. doi:10.1111/head.14505