Lacosamide: Managing uncontrolled PGTCS with an alternative adjunctive therapy

31 Dec 2021

Professor Terence O’Brien

Department of Neuroscience,
Central Clinical School,
Department of Neurology,
Alfred Health,
Monash University,

Primary generalized tonic-clonic seizures (PGTCS) are types of idiopathic generalized epilepsies (IGEs).1 They could lead to sudden unexpected death in epilepsy (SUDEP), especially in patients with uncontrolled PGTCS.1 Adjunctive therapy is needed for these patients to better control their conditions, improve quality-of-life (QoL) and prevent SUDEP. At the 7th Hong Kong Neurological Congress cum 34th Annual Scientific Meeting of the Hong Kong Neurological Society, Professor Terence O’Brien presented the recently published data of lacosamide as an adjunctive therapy to manage uncontrolled PGTCS in patients with IGEs.

Limitations of existing treatment options for uncontrolled PGTCS

According to the National Institute for Health and Care Excellence (NICE) guidelines, the first-line treatment options for PGTCS include valproate and lamotrigine.3 However, up to 12% of epilepsy patients are drug-resistant or uncontrolled, thus requiring adjunctive therapies.4

Currently, available options for adjunct pharmacotherapies include the first generation of anti-seizure medications (ASMs) such as clobazam and clonazepam, but many clinicians are worried about their safety profiles and drug-drug interactions.3 As patients' clinical response may vary greatly, therapeutic drug monitoring is often required for these agents to assess patients' response.5 Although newer alternatives such as perampanel provide greater convenience to patients, their increased risks of psychiatric adverse events (AEs), such as aggression and homicidal ideation, are of great concern to many physicians.6 Therefore, an alternative adjunctive therapy with a better safety profile and good efficacy is very much needed for patients with uncontrolled PGTCS.

Efficacy and safety of lacosamide as an oral adjunct

Lacosamide is a recently approved and newly available adjunctive alternative in Hong Kong for the treatment of uncontrolled PGTCS patients. It reduces seizure occurrences by selectively enhancing the slow inactivation of voltage-gated sodium channel.7 Its high clinical efficacy and relatively favorable safety profile were demonstrated by the VALOR study.8

VALOR is a recent, double-blinded, placebo-controlled, multicenter study, in which the efficacy of oral adjunctive lacosamide for uncontrolled PGTCS patients was evaluated.8 A total of 242 patients aged 4 years or above with a history of generalized seizures (99.6% had tonic-clonic seizures) were recruited and randomized 1:1 into the lacosamide and placebo arms.8 The primary outcome was the time to second PGTCS within the 24-week treatment period.8 The safety and tolerability of lacosamide were also assessed.8

After 24 weeks of follow-up, the study revealed a 46% risk reduction in developing second PGTCS in the lacosamide group, compared with the placebo group [Kaplan-Meier survival estimates: 55.27% vs. 33.37%; HR=0.54; 95% CI: 0.377-0.774, p<0.001] (Figure 1).8 A higher proportion of patients in the lacosamide group attained ≥50% (68.1% vs. 46.3%) and ≥75% (57.1% vs. 36.4%) reduction from baseline in the 28-day PGTCS frequency, compared to the placebo group.8

The median time to second PGTCS could not be estimated for the lacosamide group since >50% of patients on lacosamide treatment did not experience another episode of PGTCS.8 In particular, the Kaplan-Meier estimated freedom from PGTCS at the end of week 24 for the lacosamide group, was significantly lower than the placebo group (31.3% vs. 17.2%, p=0.011).8

The VALOR study has demonstrated a high tolerability of adjunctive lacosamide treatment among uncontrolled PGTCS patients. Dizziness, somnolence, and headaches were the treatment-emergent adverse events (TEAEs) that occurred in more than 10% of patients in the lacosamide group.8 The findings were consistent with the previous studies of lacosamide, and no new safety signal was observed.


Since uncontrolled PGTCS are important risk factors of SUDEP, adjunctive treatment with appropriate pharmacological agents is crucial to controlling the disease and preventing the disastrous consequences. However, physicians are concerned about the limitations of existing treatment options, such as perampanel. The recent approval of adjunctive lacosamide treatment in Hong Kong may improve the situation. With its demonstrated high efficacy and favorable safety profile, lacosamide can now offer patients with uncontrolled PGTCS a viable alternative to control their illnesses, enabling them to enjoy a higher QoL.

* In Hong Kong, VIMPAT® (lacosamide) is indicated as monotherapy and adjunctive therapy in the treatment of partial-onset seizures with or without secondary generalization in adults, adolescents, and children from 4 years of age with epilepsy. VIMPAT® (lacosamide) is not indicated for the treatment of primary generalized tonic-clonic seizure in Hong Kong. This advertorial may contain off-label information. The use of VIMPAT® (lacosamide) in any way other than that specified by the Summary of Product Characteristics is off-label and cannot be recommended by UCB Pharma (Hong Kong) Limited. Please consult your local product information.

Approved on 20/12/2021

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