New Indication for VIMPAT (lacosamide): UCB's Anti-Epileptic Drug Approved by FDA as Monotherapy in Treatment of Patient With Partial-Onset Seizures

PRESS RELEASE

Brussels (Belgium), September 1, 2014— UCB announced today that the U.S. Food and Drug Administration (FDA) has approved a 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.¹ This is a new indication for VIMPAT® which is already approved in the U.S. as adjunctive treatment for partial-onset seizures in patients in this age group.¹ 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 today 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.¹

“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 U.S. 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.

VIMPAT® Monotherapy

The new U.S. 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.¹ 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.¹

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. Additional important safety information for VIMPAT® in the U.S. is available below.¹

VIMPAT® Single Loading Dose

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.¹

VIMPAT® in the European Union

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.³

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.⁴

About VIMPAT®^1,3

VIMPAT® is approved in the U.S. 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 U.S.

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.

Important safety information about VIMPAT® in the U.S. and the European Union is available below.

IMPORTANT SAFETY INFORMATION ABOUT VIMPAT® IN THE U.S.

Warnings and Precautions

• Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs), including VIMPAT®, increase the risk of suicidal behavior and ideation. Patients taking VIMPAT® should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Patients and caregivers should also be advised 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. Accordingly, patients should be advised not to drive a car or to operate other complex machinery until they are familiar with the effects of VIMPAT® on their ability to perform such activities.
• Cardiac Rhythm and Conduction Abnormalities: PR interval prolongation Dose-dependent prolongations in PR interval with VIMPAT® have been observed in clinical studies in patients and in healthy volunteers. Second degree and complete AV block have been reported in patients in pain studies and in patients with seizures. When VIMPAT® is given with other drugs that prolong the PR interval, further PR prolongation is possible. VIMPAT® should be used with caution in patients with known cardiac conduction problems (e.g., marked first-degree AV block, second-degree or higher AV block and sick sinus syndrome without pacemaker), sodium channelopathies (e.g., Brugada Syndrome), or with severe cardiac disease such as myocardial ischemia or heart failure, or structural heart disease. VIMPAT® should be used with caution in patients on concomitant medications that prolong PR interval, because of a risk of AV block or bradycardia, e.g., beta-blockers and calcium channel blockers. In such patients, obtaining an ECG before beginning VIMPAT®, and after VIMPAT® is titrated to steady-state, is recommended. In addition, these patients should be closely monitored if they are administered VIMPAT® through the intravenous route. 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: Patients should be advised that VIMPAT® may cause syncope.
• Withdrawal of Antiepileptic Drugs: VIMPAT® should be gradually withdrawn (over a minimum of 1 week) to minimize the potential of increased seizure frequency.
• Multiorgan Hypersensitivity Reactions: Multiorgan hypersensitivity reactions (also known as Drug Reaction with Eosinophilia and Systemic Symptoms, or DRESS) have been reported with antiepileptic drugs. If this reaction is suspected, VIMPAT® should be discontinued and alternative treatment started.
• Phenylketonurics: VIMPAT® oral solution contains aspartame, a source of phenylalanine. A 200 mg dose of VIMPAT® oral solution (equivalent to 20 mL) contains 0.32 mg of phenylalanine. Adverse Reactions
• Adjunctive therapy: In the 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 clinical trial, adverse reactions were generally similar to those observed and attributed to drug in adjunctive placebo controlled trials, with the exception of insomnia (observed at a higher rate of ≥2%).
• Injection: In adjunctive therapy clinical trials, adverse reactions with intravenous administration generally were similar to those observed with the oral formulation, although intravenous administration was associated with local adverse events 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, sWhen 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.

References:

• VIMPAT® U.S. Prescribing Information. Accessed 1st September 2014 from http://www.vimpat.com/PDF/vimpat_PI.pdf
• Wechsler, R et al. Conversion to lacosamide monotherapy in the treatment of focal epilepsy: Results from a historical-controlled, multicenter, double-blind study. Epilepsia; 2014; 55(7): 1088-1098.
• VIMPAT® EU Summary of Product Characteristics. Accessed 21st July 2014 from http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000863/WC500050338.pdf
• ClinicalTrials.gov Identifier: NCT01243177 Accessed 21st July 2014 from http://clinicaltrials.gov/ct2/show/NCT01243177?term=Vimpat+Monotherapy&rank=2
• ClinicalTrials.gov Identifier NCT00520741 Accessed 21st July 2014 from http://clinicaltrials.gov/ct2/show/NCT00520741?term=Vimpat+Monotherapy&rank=4
• Epilepsy Foundation: About Epilepsy: The Basics Accessed 21st July 2014 from http://www.epilepsy.com/learn/about-epilepsy-basics
• Epilepsy Foundation. What is Epilepsy?. Accessed 21st July 2014 from http://www.epilepsy.com/learn/epilepsy-101/what-epilepsy UCB News LCM-PRR-033383-072014
• NINDS/NIH. Seizures and Epilepsy. Accessed 21st July 2014 from http://www.ninds.nih.gov/disorders/epilepsy/detail_epilepsy.htm#196923109
• St Louis, EK et al. Antiepileptic drug monotherapy: The initial approach in epilepsy management. Curr Neuropharmacol. 2009;7(2):77-82.
• Institute of Medicine. Epilepsy Across the Spectrum. Promoting Health and Understanding, Washington, DC: The National Academic Press, 2012 brief report. Accessed 30th July 2014 from http://www.iom.edu/~/media/Files/Report%20Files/2012/Epilepsy/epilepsy_rb.pdf