Vimpat® (lacosamide) provided sustained efficacy and good tolerability for up to 8 years in patients with partial onset seizures

For the attention of accredited medical writers only

Brussels (Belgium) and Rome, 31st August 2011, 0700 CET – Consistent evidence that adjunctive treatment with Vimpat^® (lacosamide) was generally well tolerated and associated with a sustained reduction in partial onset seizures for up to 8 years, was presented this week at the 29^th International Epilepsy Congress in Rome, Italy (28^th August-1^st September)^1-4.

“These data showed that the seizure control and tolerability seen with lacosamide in pivotal phase III clinical trials were maintained during open label long term studies, and they provide additional clinical data to neurologists searching for long term solutions for adult patients with poorly controlled partial onset seizures,” said Dr Robert F. Leroy, Neurological Clinic of Texas, Dallas, Texas, USA.

A further study announced at the Congress – VITOBA™ (VIpatT added to One Baseline AED) - is investigating whether lacosamide has additive or synergistic effects when added to single agent AED treatment for partial onset seizures in a real life clinical setting⁵. Analysis of data from this six month, prospective, non-interventional study of 500 evaluable patients with partial onset seizures should provide comparative insights into the effects of adding lacosamide to a single “sodium channel” or “non-sodium channel” AED.

Lacosamide was launched in the European Union in September 2008, as adjunctive therapy for the treatment of partial onset seizures with or without secondary generalization in patients with epilepsy, aged 16 years and older. Lacosamide solution for infusion may be used when oral administration is temporarily not feasible.

In the US, Vimpat^® tablets and injection for intravenous use were launched in May 2009 as an add-on therapy for the treatment of partial onset seizures in patients with epilepsy who are 17 years and older. Lacosamide injection is a short-term replacement when oral administration is not feasible in these patients. Lacosamide oral solution was launched in June 2010.

The maximum recommended daily dose for Vimpat^® in the European Union and the US is 400 mg/day.

Long term efficacy and safety from open-label extension trials SP756, SP774 and SP615

SP756¹

• 308 patients enrolled to open-label lacosamide for <5.5 years
• Median reduction in 28-day seizure frequency and ≥50% responder rate during the treatment period from baseline of SP754 phase III trial was 48.5% and 48.2%, respectively
• Of patients exposed to lacosamide ≥2 years, 3.1% remained seizure-free through ≥2 years
• Primary reasons for discontinuation: lack of efficacy (26%); AEs (11%)
• Common TEAEs (≥15%): dizziness, headache, contusion, nausea, convulsion, nasopharyngitis, fall, vomiting, diplopia. TEAEs that led to discontinuation in ≥1.0% of patients were dizziness (1.6%) and convulsion (1.0%)

SP774²

• 376 patients enrolled to open-label lacosamide for <5.5 years
• Median reduction in 28-day seizure frequency and ≥50% responder rate during the treatment period from baseline of SP755 phase III trial was 49.9% and 50%, respectively
• Of patients exposed to lacosamide for ≥1 year, 3.2% remained seizure-free for ≥1 year
• Common AEs (≥10%) were dizziness (24%), headache (14%), diplopia (14%), and nasopharyngitis (14%)
• Discontinuations due to AE were 9% with dizziness (1.3%) leading to discontinuation in >1% of patients

SP615³

• 370 patients enrolled to open-label lacosamide for < 8 years
• Median reduction in 28-day seizure frequency and ≥50% responder rate during the treatment period from baseline of previous trials was 50.8% and 51.2%, respectively
• Common TEAEs (≥15%) were dizziness, headache, nausea, diplopia, fatigue, upper respiratory tract infection, nasopharyngitis, contusion, and coordination abnormal
• Discontinuations due to TEAEs were 12.7% with dizziness and convulsion leading to discontinuation in ≥1% of patients

Summary of long term efficacy

* % patients with years of lacosamide exposure

Summary of long term safety open-label extension trial, SP926⁴

• 97 patients enrolled to lacosamide for < 5.5 years

• TEAEs (incidence ≥15%) included dizziness (44.3%), diplopia (17.5%), and vomiting (16.5%) and most were mild/moderate in intensity. Only one serious AE (SAE) occurred in more than one patient (convulsion, n=2)

• One patient discontinued due to SAEs (supraventricular arrhythmia and atrial fibrillation) and continued lacosamide after treatment of the SAEs. One TEAE led to discontinuation in more than one patient (dizziness, n=3)

• Median clinical laboratory values remained within normal range and changes from baseline were not of clinical relevance. Small increases in mean PR interval and QRS duration were consistent with the known lacosamide safety profile and did not vary with lacosamide exposure.

Important safety information about Vimpat^® in the EU and EEA
Vimpat^® is indicated as adjunctive therapy in the treatment of partial-onset seizures with or without secondary generalization in patients with epilepsy aged 16 years and older. Lacosamide solution for infusion is an alternative for patients when oral administration is temporarily not feasible. Contraindications: Hypersensitivity to the active substance or any of the excipients; known second- or third-degree atrioventricular (AV) block. Special warnings and precautions for use: Treatment with lacosamide has been associated with dizziness which could increase the occurrence of accidental injury or falls. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medicine. Prolongations in PR interval with lacosamide have been observed in clinical studies. Cases with second and third degree AV block associated with lacosamide treatment have been reported in post-marketing experience. Lacosamide should be used with caution in patients with known conduction problems or severe cardiac disease such as a history of myocardial infarction or heart failure. Caution should especially be exerted when treating elderly patients as they may be at an increased risk of cardiac disorders or when lacosamide is used in combination with products known to be associated with PR prolongation. Second degree or higher AV block has been reported in post-marketing experience. In the placebo-controlled trials of lacosamide in epilepsy patients, atrial fibrillation or flutter were not reported; however both have been reported in open-label epilepsy trials and in post-marketing experience. Patients should be made aware of the symptoms of second-degree or higher AV block (e.g. slow or irregular pulse, feeling of lightheaded and fainting) and of the symptoms of atrial fibrillation and flutter (e.g. palpitations, rapid or irregular pulse, shortness of breath). Patients should be counseled to seek medical advice should any of these symptoms occur. Suicidal ideation and behavior have been reported in patients treated with anti-epileptic agents. Therefore patients should be monitored for signs of suicidal ideation and behaviors and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behavior emerge. Lacosamide syrup contains sodium methylhydroxybenzoate (E219), which may cause allergic reaction (possibly delayed). Patients with rare hereditary problems of fructose intolerance should not take this medicine. The syrup contains aspartame (E951), a source of phenylalanine, which may be harmful for people with phenylketonuria. Both the syrup and solution for infusion contain sodium. To be taken into consideration for patients on a controlled sodium diet. Effects on ability to drive and use machines: Lacosamide may have minor to moderate influence on the ability to drive and use machines. Lacosamide treatment has been associated with dizziness and blurred vision. Accordingly patients should be advised not to drive a car or to operate other potentially hazardous machinery until they are familiar with the effects of lacosamide on their ability to perform such activities. Laboratory abnormalities: Abnormalities in liver function tests have been observed in controlled trials with lacosamide in adult patients with partial-onset seizures who were taking 1-3 concomitant antiepileptic drugs. Elevations of ALT to ≥3XULN occurred in 0.7% (7/935) of lacosamide patients and 0% (0/356) of placebo patients. Multiorgan Hypersensitivity Reactions: Multiorgan hypersensitivity reactions have been reported in patients treated with some antiepileptic agents. These reactions are variable in expression but typically present with fever and rash and can be associated with involvement of different organ systems. Potential cases have been reported rarely with lacosamide and if multiorgan hypersensitivity reaction is suspected, lacosamide should be discontinued. Undesirable effects: The most common adverse reactions (≥10 %) are dizziness, headache, diplopia, and nausea. Other common adverse reactions (≥1%<10 %) are depression, confusional state, insomnia, balance disorder, coordination abnormal, memory impairment, cognitive disorder, somnolence, tremor, nystagmus, hypoesthesia, dysarthria, disturbance in attention, vision blurred, vertigo, tinnitus, vomiting, constipation, flatulence, dyspepsia, dry mouth,

pruritus, rash, muscle spasms, gait disturbance, asthenia, fatigue, irritability, injection site pain or discomfort (specific to solution for infusion), irritation (specific to solution for infusion), fall, and skin laceration. Refer to the European Summary of Product Characteristics for other adverse reactions and full prescribing information. Date of revision: 06 May 2011.

http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000863/WC500050338.pdf (Accessed 19th May 2011)

Important safety information about Vimpat^® in the U.S.
Warnings and Precautions
AEDs 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 should be advised that Vimpat^® may cause dizziness, ataxia, and syncope. Caution is advised for patients with known cardiac conduction problems, who are taking drugs known to induce PR interval prolongation, or with severe cardiac disease. In patients with seizure disorders, Vimpat^® should be gradually withdrawn to minimize the potential of increased seizure frequency. Multiorgan hypersensitivity reactions have been reported with AEDs. If this reaction is suspected, treatment with Vimpat^® should be discontinued.

For full prescribing information on Vimpat^®, visit http://www.vimpat.com/prescribing-information.aspx, and for more information on Vimpat^®, visit Vimpat.com or contact UCB at (800) 477-7877.

Vimpat^® is a Schedule V controlled substance.

Vimpat^® is a registered trademark under license from Harris FRC Corporation.

References
1. Husain A, Faught E, Chung S, Isojarvi J, McShea C, Doty P. Long-term safety and efficacy of lacosamide as adjunctive therapy in patients with uncontrolled POS: results from a Phase III open-label extension trial. Presented at the 29^th International Epilepsy Congress in Rome, Italy (28^th August-1^st September)
2. Rosenow F, Kelemen A, Ben-Menachem E, McShea C, Isojarvi J, Doty P. Long-term adjunctive lacosamide in patients with uncontrolled partial-onset seizures: results from the SP774 Phase III open-label extension trial. Presented at the 29^th International Epilepsy Congress in Rome, Italy (28^th August-1^st September)
3. Rosenfeld W, Fountain NB, Kaubrys G, Ben-Menachem E, McShea C, Isojarvi J, Doty P and the SP615 Study Team. Lacosamide: long-term safety and efficacy in partial-onset seizures. Presented at the 29^th International Epilepsy Congress in Rome, Italy (28^th August-1^st September)
4. LeRoy RF, Krauss G, Fountain NB, Dilley D, D’Cruz O’N, Doty P. Lacosamide: long-term safety in partial onset seizures. Presented at the 29^th International Epilepsy Congress in Rome, Italy (28^th August-1^st September)
5. Runge U, Mayer Th, Arnold s, Kumke Th, Noack-Rink M. An ongoing post-marketing study evaluating lacosamide as adjunctive therapy to one baseline antiepileptic drug in epilepsy patients – SP0973 VITOBA Study (VImpaT added to One Baseline AED). Presented at the 29^th International Epilepsy Congress in Rome, Italy (28^th August-1^st September)
6. Lacosamide Summary of Product Characteristics (EU). http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000863/WC500050338.pdf (Accessed 19th May 2011)
7. Vimpat^® Prescribing Information (US) http://www.vimpat.com/prescribing-information.aspx

For further information

Eimear O Brien, Associate Director, Global CNS Communications
T +32 2 559 9271, eimear.obrien@ucb.com

About UCB
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 8 500 people in about 40 countries, the company generated revenue of EUR 3.2 billion in 2010. UCB is listed on Euronext Brussels (symbol: UCB).

Forward-looking statements
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