The US Food and Drug Administration (FDA) has approved UCB's supplemental new drug application (sNDA) for Vimpat (lacosamide) C-V as monotherapy in the treatment of partial-onset seizures in patients with epilepsy aged 17 years and older.

This is a new indication for Vimpat which is already approved in the US as adjunctive treatment for partial-onset seizures in patients in this age group. This new indication means that adults with partial-onset seizures can be initiated on Vimpat monotherapy, and patients already on an anti-epileptic drug can be converted to Vimpat monotherapy.

UCB also announced that the FDA has approved a new single loading dose administration option for all formulations of Vimpat, when used as monotherapy or adjunctive therapy in the treatment of partial-onset seizures in patients with epilepsy aged 17 years and older.

“People living with epilepsy have individual needs. It’s our aim at UCB to provide as many patients as possible with various options to reduce their seizures. Now, physicians and epilepsy patients in the US have more Vimpat options to treat partial-onset seizures – Vimpat as an initial monotherapy, converting to Vimpat monotherapy and Vimpat as an adjunctive therapy. In addition, based on individual patients’ needs, physicians can choose between Vimpat formulations - tablets, oral solution or injection. Also, initiation of Vimpat as a single loading dose provides physicians with an alternative administration option to the standard titration schedule,” said Professor Dr. Iris Loew Friedrich, chief medical officer and executive vice president, UCB.

The new US monotherapy approval for Vimpat is based on a phase 3 historical-control conversion to lacosamide monotherapy study in adult epilepsy patients with partial-onset seizures. The study met its primary endpoint, demonstrating that the exit percentage, defined as the estimated percentage of patients meeting pre-defined exit criteria, for patients converting to lacosamide 400 mg/day was significantly lower than the historical control exit percentage, used as a comparator. Lacosamide 300 mg/day also met the pre-specified criteria for efficacy.

The most common adverse reactions in the monotherapy study were similar to those seen in adjunctive therapy studies; however, one adverse reaction, insomnia, was observed at a rate of =2% and was not reported at a similar rate in previous studies. Insomnia has also been observed in postmarketing experience. Because this study did not include a placebo control group, causality could not be established. In adjunctive therapy studies, the most common adverse reactions (=10% and greater than placebo) were dizziness, headache, nausea and diplopia.

The new single loading dose administration option for Vimpat as monotherapy or adjunctive treatment of partial-onset seizures in adults with epilepsy allows the initiation of Vimpat as a single loading dose of 200 mg (oral or injection), followed approximately 12 hours later by a 100 mg twice daily dose (200 mg/day). The most common loading dose adverse events (=5%) were dizziness, headache, paraesthesia and gait disturbance. The loading dose should be administered with medical supervision considering the Vimpat pharmacokinetics and increased incidence of CNS adverse reactions.

In the European Union, Vimpat is approved as adjunctive therapy for the treatment of partial-onset seizures with or without secondary generalization in adult and adolescent (16-18 years) patients with epilepsy. Vimpat may also be initiated with a single loading dose of 200 mg, followed approximately 12 hours later by a 100 mg twice daily (200 mg/day) maintenance dose regimen. Additional important information on Vimpat loading dose in the European Union is available below. Vimpat is not approved in the European Union as monotherapy.

A non-inferiority monotherapy study is underway to support the potential monotherapy filing with the European Medicines Agency. The study aims to compare the efficacy and safety of lacosamide to carbamazepine controlled-release as monotherapy in newly or recently newly diagnosed patients (= 16 years) with partial-onset seizures.

The phase 3 study was a historical-control, multicenter, randomized study that evaluated the efficacy and safety of conversion to lacosamide 400 mg/day monotherapy in adult epilepsy patients with partial-onset seizures. The study enrolled 425 patients, aged 16–70 years, on stable doses of 1-2 AEDs and experiencing 2-40 partial-onset seizures per 28 days during the 8 week prospective baseline. Patients taking 2 AEDs must have been taking =50% of the minimum recommended maintenance dose for 1 of the 2 AEDs, per US product label.

Patients were randomized to lacosamide 400 or 300 mg/day (3:1 ratio), starting at 200 mg/day (100 mg/day twice daily) and titrated over 3 weeks (100 mg/day each week) to the randomized dose. Patients then entered the 16-week lacosamide maintenance phase, which included a 6-week background AED withdrawal phase and a 10-week lacosamide monotherapy phase. Patients were evaluated from the first day of tapering of the background AEDs and required to discontinue the study if they experienced any of the predefined exit events defined by an increase in seizure frequency, duration or severity.

The primary efficacy assessment was the percentage of patients receiving lacosamide 400 mg/day who met one or more of the pre-defined exit criteria by day 112 (end of lacosamide maintenance phase) compared with the historical control. The historical control consisted of a pooled analysis of the control groups from 8 studies of similar design, which utilized a sub-therapeutic dose of an AED as a control. For the lacosamide 400 mg/day group, the estimated percentage of patients meeting at least one exit criterion by day 112 was 30.0% (95% Confidence Interval [CI]: 24.6%, 35.5%). The upper limit of the 2-sided 95% CI (35.5%) was below the threshold of 65.3% derived from the historical control data, meeting the pre-specified criteria for efficacy.

In the monotherapy trial, 16% of patients randomized to receive lacosamide at the recommended doses of 300 and 400 mg/day discontinued from the trial as a result of an adverse event. The adverse reaction most commonly (=1% on lacosamide) leading to discontinuation was dizziness. Adverse reactions observed in this study were generally similar to those observed and attributed to drug in adjunctive placebo-controlled studies. Dizziness, headache, nausea, somnolence, and fatigue were all reported at lower incidences during the AED withdrawal phase and monotherapy phase, compared with the titration phase.

Epilepsy is a chronic neurological disorder affecting approximately 65 million people worldwide and more than 2 million people in the US. It is the fourth most common neurological disorder in the U.S. Anyone can develop epilepsy; it occurs across all ages, races and genders and is defined as two or more unprovoked seizures that occur at least 24 hours apart. Anti-epileptic drug monotherapy is in general the initial management approach in epilepsy care, since many patients may be successfully managed with the first or second monotherapy utilized.

Vimpat is approved in the US as tablets, injection and oral solution as monotherapy or adjunctive therapy in the treatment of partial-onset seizures in people with epilepsy ages 17 years and older. Vimpat injection is a short-term replacement when oral administration is not feasible in these patients. The availability of the oral tablets, oral solution, and intravenous (IV) injection formulations permits flexibility in administration.

A single loading dose administration option is also approved in the U.S. for all formulations of Vimpat when used as monotherapy or adjunctive therapy in the treatment of partial-onset seizures in patients with epilepsy aged 17 years and older.

Since the initial launch of Vimpat tablets and injection in May 2009, there have been more than 200,000 Vimpat patient exposures in the US.

In the European Union, Vimpat (film-coated tablets, syrup and solution for infusion) is approved as adjunctive therapy for the treatment of partial-onset seizures with or without secondary generalization in adult and adolescent (16-18 years) patients with epilepsy. Vimpat is also approved in the European Union for initiation as a single loading dose of 200 mg, followed approximately 12 hours later by a 100 mg twice-daily maintenance dose regimen.


UCB, Brussels, Belgium is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system.