- Study met primary and secondary endpoints of significantly lowering the risk of developing a second primary generalized tonic-clonic seizure (PGTCS) during a 24-week treatment and a significantly higher rate of freedom from PGTCS during the treatment period compared with placebo
- Lacosamide was generally tolerated by patients enrolled in the study
- Regulatory reviews, based, in part, on these data, are currently underway in the U.S., EU, Japan, and Australia
- VIMPAT® is currently not approved for PGTCS in any country in the world
Atlanta, Ga. (31 August 2020, 7am ET) - UCB, a global biopharmaceutical company, today announced the publication of the Phase 3 study results of VIMPAT® (lacosamide) CV as adjunctive treatment for uncontrolled primary generalized tonic-clonic seizures (PGTCS), in the Journal of Neurology, Neurosurgery & Psychiatry.1
The Phase 3 study enrolled 242 patients (≥4 years of age) with idiopathic generalized epilepsy (IGE) who were randomized 1:1 to receive lacosamide or placebo (twice daily) in addition to their current epilepsy treatment. The primary endpoint was time to second primary generalized tonic-clonic seizure (PGTCS) during the 24-week (166-day) treatment period.
Treatment with lacosamide resulted in a significantly lower risk of developing a second PGTCS during the 24-week treatment (HR 0.540; p<0.001) and a significantly higher rate of freedom from PGTCS during the treatment period compared with placebo (31.3% vs 17.2%, p=0.011). Lacosamide was generally tolerated in patients with IGE and PGTCS. The most common treatment-emergent adverse events (≥10%) with lacosamide were dizziness (23.1%), somnolence (16.5%) and headache (14.0%). The incidences of dizziness and headache were numerically higher with lacosamide than placebo.
VIMPAT® is currently not approved for PGTCS in any country in the world. Regulatory reviews for use of VIMPAT as adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in patients with idiopathic generalized epilepsy four years of age and older compared to placebo are currently underway in the U.S., EU, Japan, and Australia.
“This Phase 3 trial demonstrated that by adding lacosamide to existing anti-seizure medications, IGE patients with uncontrolled primary generalized tonic-clonic seizures experienced a higher rate of seizure freedom, suggesting lacosamide could be a valuable adjunctive therapy in this patient population,” said David Vossler, MD, FAAN FACNS FAES, Department of Neurology, University of Washington, USA.
IGEs account for 20%–40% of all epilepsies2 and are characterized by different generalized seizure types (absence, myoclonic and PGTCS).3 Patients living with generalized tonic-clonic seizures have an increased risk of injury4 and those who experienced three or more in one year had a fifteen-fold increased risk of sudden unexpected death in epilepsy.5
“UCB remains committed to strengthening our leadership in epilepsy and to investigating new approaches and innovative solutions to deliver improved outcomes and experiences to the global epilepsy community. This applies equally to our current expansive in-market epilepsy portfolio as well as to our exciting pipeline,” explained Charl van Zyl, Executive Vice President & Head of Neurology Solutions, UCB.
About the Study1
The study (SP0982; NCT02408523) was a Phase 3, double-blind, randomized, placebo-controlled, multicenter study in patients with IGE and PGTCS taking 1–3 concomitant anti-epileptic drugs (AEDs). The primary outcome was time to second PGTCS during 24-week treatment. 242 eligible patients were randomized 1:1 to receive lacosamide or placebo (twice daily). Patients were eligible if they were ≥4 years of age with a confirmed diagnosis of IGE experiencing classifiable PGTCS. The treatment period continued until one of the following occurred: completion of ≥6 weeks of the treatment period and occurrence of two or more PGTCS, completion of the 24-week treatment period without occurrence of two PGTCS, or the 125th event occurred in the trial.
About VIMPAT® (lacosamide) CV in the U.S.6
VIMPAT® was approved in the U.S. in 2008 as an add-on therapy for adult patients. VIMPAT was approved as monotherapy for adults in August 2014, and as monotherapy or adjunctive therapy in patients four years of age and older with partial-onset seizures in 2017. VIMPAT is available in three formulations: oral tablets, oral solution, and intravenous (IV) injection.
VIMPAT U.S. INDICATION AND IMPORTANT SAFETY INFORMATION
VIMPAT® is indicated for the treatment of partial-onset seizures in patients 4 years of age and older.
As the safety of VIMPAT injection in pediatric patients has not been established, VIMPAT injection is indicated for the treatment of partial-onset seizures only in adult patients (17 years of age and older).
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
- Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs), including VIMPAT, increase the risk of suicidal behavior and ideation. Monitor patients taking VIMPAT for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Advise patients and caregivers to be alert for these behavioral changes and to immediately report them to the healthcare provider.
- Dizziness and Ataxia: VIMPAT may cause dizziness and ataxia. In adult clinical trials, the onset of dizziness and ataxia was most commonly observed during titration. Advise patients not to drive, operate complex machinery, or engage in other hazardous activities until they are familiar with the effects of VIMPAT on their ability to perform such activities. Dizziness and ataxia were also observed in pediatric clinical trials.
- Cardiac Rhythm and Conduction Abnormalities
PR Interval Prolongation, Atrioventricular Block, and Ventricular Tachyarrhythmia
Dose-dependent prolongations in PR interval with VIMPAT have been observed in clinical studies in adult patients and in healthy volunteers. When VIMPAT is given with other drugs that prolong the PR interval, further PR prolongation is possible.
In the postmarketing setting, there have been reports of cardiac arrhythmias in patients treated with VIMPAT, including bradycardia, AV block, and ventricular tachyarrhythmia, which have rarely resulted in asystole, cardiac arrest, and death. Most, although not all, cases have occurred in patients with underlying proarrhythmic conditions, or in those taking concomitant medications that affect cardiac conduction or prolong the PR interval. These events have occurred with both oral and intravenous routes of administration and at prescribed doses as well as in the setting of overdose.
VIMPAT should be used with caution in patients with underlying proarrhythmic conditions such as known cardiac conduction problems (e.g., marked first-degree AV block, second-degree or higher AV block, and sick sinus syndrome without pacemaker), severe cardiac disease (such as myocardial ischemia or heart failure, or structural heart disease), and cardiac sodium channelopathies (e.g., Brugada Syndrome).
VIMPAT should also be used with caution in patients on concomitant medications that affect cardiac conduction, including sodium channel blockers, beta-blockers, calcium channel blockers, potassium channel blockers, and medications that prolong the PR interval. In such patients, obtaining an ECG before beginning VIMPAT, and after VIMPAT is titrated to steady-state maintenance dose, is recommended. In addition, these patients should be closely monitored if they are administered VIMPAT through the intravenous route. Patients should be made aware of and report cardiac signs or symptoms to their healthcare provider right away.
Atrial Fibrillation and Atrial Flutter
VIMPAT administration may predispose to atrial arrhythmias (atrial fibrillation or flutter), especially in patients with diabetic neuropathy and/or cardiovascular disease.
- Syncope: VIMPAT may cause syncope in adult and pediatric patients.
- Withdrawal of Antiepileptic Drugs: Gradually withdraw VIMPAT (over a minimum of 1 week) to minimize the potential of increased seizure frequency.
- Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Also known as multi- organ hypersensitivity, has been reported with antiepileptic drugs, including VIMPAT. Some of these events have been fatal or life-threatening. If signs or symptoms are present, immediately evaluate the patient. Discontinue VIMPAT if an alternative etiology for the signs and symptoms cannot be established.
- Risks in Patients with Phenylketonuria: VIMPAT oral solution contains aspartame, a source of phenylalanine, which can be harmful in patients with phenylketonuria (PKU). A 200 mg dose of VIMPAT oral solution (equivalent to 20 mL) contains 0.32 mg of phenylalanine.
- Adjunctive therapy: In the adult placebo-controlled clinical trials, the most frequently seen adverse reaction with VIMPAT was dizziness (31% vs 8% placebo). Other common adverse reactions occurring in ≥10 percent of VIMPAT-treated patients, and greater than placebo, were headache, nausea, and diplopia.
- Monotherapy: In the adult clinical trial, adverse reactions were generally similar to those observed and attributed to drug in adjunctive placebo-controlled trials, with the exception of insomnia (occurred at a higher rate of ≥2%).
- Pediatric patients: Adverse reactions reported in clinical studies of pediatric patients 4 to less than 17 years of age were similar to those seen in adult patients.
- Injection: In adult adjunctive therapy clinical trials, adverse reactions with intravenous administration generally were similar to those that occurred with the oral formulation, although intravenous administration was associated with local adverse reactions such as injection site pain or discomfort (2.5%), irritation (1%), and erythema (0.5%). When administering a loading dose, the incidence of CNS adverse reactions, such as dizziness, somnolence, and paresthesia, may be higher with 15-minute administration than over a 30- to 60- minute period.
VIMPAT injection is for intravenous and adult use only when oral administration is temporarily not feasible. The loading dose for adult patients should be administered with medical supervision considering the VIMPAT pharmacokinetics and increased incidence of CNS adverse reactions. The safety of VIMPAT injection and the use of a loading dose in pediatric patients have not been studied. Dosage adjustments are recommended for patients with mild or moderate hepatic impairment or severe renal impairment. Use in patients with severe hepatic impairment is not recommended. Perform dose titration with caution in all patients with renal and/or hepatic impairment.
VIMPAT is a Schedule V controlled substance.
Epilepsy is the main symptom of a variety of chronic disorders of the brain. It is the fourth most common neurological condition worldwide and affects approximately 65 million people.7 Anyone can develop epilepsy; it occurs across all ages, races and genders, and is defined as one or more unprovoked epileptic seizures with a risk of further seizures.8
About UCB in Epilepsy
UCB has a rich heritage in epilepsy with over 30 years of experience in the research and development of anti-epileptic drugs. As a company with a long-term commitment to epilepsy research, our goal is to address unmet medical needs. Our scientists are proud to contribute to advances in the understanding of epilepsy and its treatment. We partner and create super-networks with world-leading scientists and clinicians in academic institutions, pharmaceutical companies, and other organizations who share our goals. At UCB, we are inspired by patients, and driven by science in our commitment to support patients with epilepsy.
UCB, Brussels, Belgium (www.ucb.com) 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. With more than 7,600 people in approximately 40 countries, the company generated revenue of € 4.9 billion in 2019. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCB_news
For further information, UCB:
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VIMPAT® is a registered trademark used under license from Harris FRC Corporation.
©2020 UCB, Inc., Smyrna, GA 30080. All rights reserved.
Forward looking statements UCB
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- Vossler DG, et al. Efficacy and safety of adjunctive lacosamide in the treatment of primary generalised tonic-clonic seizures: a double-blind, randomized, placebo-controlled trial. J Neurol Neurosurg Psychiatry 2020;0:1–9. doi:10.1136/jnnp-2020-323524
- Marini C., King M.A., Archer J.S., Newton M.R., Berkovic S.F. Idiopathic generalised epilepsy of adult onset: clinical syndromes and genetics. J Neurol Neurosurg Psychiatry 2003; 74(2):192–6
- Benbadis SF. Practical management issues for idiopathic generalised epilepsies. Epilepsia. 2005;46(Suppl 9):125-132.
- Asadi-Pooya AA, Nikseresht A, Yaghoubi E, et al. Physical injuries in patients with epilepsy and their associated risk factors. Seizure 2012;21:165–8.
- DeGiorgio CM, et al. Ranking the leading risk factors for sudden unexpected death in epilepsy. Front Neurol. 2017;8:473
- VIMPAT® (lacosamide) CV. U.S. Prescribing Information
- Epilepsy Foundation. Who gets epilepsy? https://www.epilepsy.com/learn/about-epilepsy-basics/what-epilepsy https://www.epilepsy.com/learn/about-epilepsy-basics/who-gets-epilepsy. Date Accessed 24th August 2020
- International League Against Epilepsy. Definition of Epilepsy 2014. https://www.ilae.org/guidelines/definition-and-classification/definition-of-epilepsy-2014. Date Accessed 24th August 2020