UCB with positive results for Vimpat® (lacosamide) in EU Phase 3 monotherapy study
- Category: Small Molecules
- Published on Thursday, 08 October 2015 10:34
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- Top-line results demonstrate non-inferiority of lacosamide to carbamazepine-CR as monotherapy on a six months seizure-freedom rate
- Building on UCB’s commitment enhancing value for people living with epilepsy
- Submission to EU regulatory authority planned in H1 2016
BRUSSELS, Belgium I October 8, 2015 I UCB today announced positive results of a Phase 3 non-inferiority study designed to compare efficacy and safety of lacosamide to carbamazepine-CR (controlled release; retard tablets) as monotherapy in newly or recently diagnosed adult patients with partial-onset seizures. The study met its primary endpoint for the proportion of patients remaining seizure free for six consecutive months of treatment. UCB plans to submit to the European Medicines Agency (EMA) these data as part of its variation file to extend the marketing authorization of lacosamide as monotherapy , which is planned in the first half of 2016.
“We are very pleased with these top-line results which reported 90% of lacosamide patients remaining seizure free for six consecutive months, demonstrating non-inferiority of lacosamide. We look forward to discussing the detailed study results with the regulatory agencies and the scientific community,” said Professor Dr Iris Loew-Friedrich, Chief Medical Officer and Executive Vice President UCB. “These encouraging data support lacosamide as monotherapy for partial onset seizures, which is already approved and launched in the United States and should soon reach patients in the EU. Lacosamide is currently available in 47 countries. Our ongoing comprehensive development program includes clinical trials in primary generalized tonic-clonic seizures as well as studies in children. We aim to make the product available to many more people living with epilepsy worldwide.”
“In recent years Vimpat® has provided value for patients requiring add-on therapy for their focal epilepsy,” said Jeff Wren, Patient Value Head Neurology and Executive Vice President UCB. “This study suggests that it may provide similar benefits as a first-line monotherapy , building on our commitment on enhancing value for those with seizure disorders at every point in their epilepsy journey.”
This Phase 3 study was an international, positive controlled, multicenter, double-blind, randomized comparison between lacosamide (200 to 600mg/day) and carbamazepine-CR (400 to 1200mg/day) used as monotherapy in 888 patients aged 16 years and older with newly or recently diagnosed epilepsy. The observed adverse events were similar to those reported in previous lacosamide studies.
These topline results will be followed by full efficacy and safety analyses and will be submitted for presentation at an upcoming epilepsy meeting.
Lacosamide (tradename Vimpat®) is approved as adjunctive therapy for the treatment of partial-onset seizures in adults with epilepsy (ages ≥ 17 years in the U.S., ages ≥ 16 years in the EU) and in the U.S. also as monotherapy. In the EU, Lacosamide is not currently approved for use as monotherapy. Important safety information for lacosamide is available below.
Vimpat® was first launched in the European Union in September 2008, 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. In countries of the EU, Vimpat® is available as film-coated tablets, syrup and solution for infusion. Lacosamide solution for infusion is an alternative for patients when oral administration is temporarily not feasible. Vimpat® tablets and injection were launched in the U.S. in May 2009 as an add-on therapy for the treatment of partial-onset seizures in people with epilepsy who are aged 17 years and older. Vimpat® injection is a short-term replacement when oral administration is not feasible in these patients. Vimpat® oral solution was launched in June 2010. The availability of the oral tablets, oral solution, and intravenous (IV) injection allows for consistent patient treatment. In Asia, Vimpat® is available Korea, Hong Kong, Malaysia, Philippines and Thailand. Vimpat® is not approved in Japan and China, regulatory submissions are planned for 2015. Important safety information about Vimpat® is available below.
Epilepsy is a disease of the brain affecting approximately 65 million people worldwide. It is defined as either the occurrence of two or more unprovoked seizures >24 hours apart or one unprovoked (or reflex) seizure and a probability of further seizures occurring over the next 10 years that is similar to the general recurrence risk (at least 60%) after two unprovoked seizures or diagnosis of an epilepsy syndrome. Although epilepsy may be linked to factors such as health conditions, race and age, it can develop in anyone at any age, and approximately 1 in 26 people will develop epilepsy in their lifetime.
About UCB in Epilepsy
UCB has a rich heritage in epilepsy with over 20 years of experience in the research and development of novel antiepileptic drugs. Every day, thousands of people use AEDs from our portfolio to help control their seizures. As a company with a long-term commitment to epilepsy research our goal is to address unmet medical needs and to deliver solutions that improve patients’ lives. 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.
About Vimpat® (lacosamide) - Important Safety Information about Vimpat® in the EU and EEA
Vimpat® (lacosamide) is indicated as adjunctive therapy in the treatment of partial-onset seizures with or without secondary generalization in adult and adolescent (16-18 years) patients with epilepsy. VIMPAT® therapy can be initiated with either oral or IV administration. A single loading dose may be initiated in patients in situations when the physician determines that rapid attainment of lacosamide steady state plasma concentration and therapeutic effect is warranted. It should be administered under medical supervision with consideration of the potential for increased incidence of CNS adverse reactions. Administration of a loading dose has not been studied in acute conditions such as status epilepticus. 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 VIMPAT® 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 VIMPAT® have been observed in clinical studies. Cases with second- and third-degree AV block associated with VIMPAT® treatment have been reported in post-marketing experience. VIMPAT® 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 VIMPAT® is used in combination with products known to be associated with PR prolongation. In the placebo-controlled trials of VIMPAT® 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 behaviour have been reported in patients treated with anti-epileptic agents in several indications. Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge. VIMPAT® syrup contains sodium methyl parahydroxybenzoate (E219) which may cause allergic reactions (possibly delayed). It contains 3.7 g sorbitol (E420) per dose (200 mg lacosamide), corresponding to a calorific value of 9.7 kcal. 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. VIMPAT® syrup and the solution for infusion contain sodium, which should be taken into consideration for patients on a controlled sodium diet. Effects on ability to drive and use machines: VIMPAT® may have minor to moderate influence on the ability to drive and use machines. VIMPAT® treatment has been associated with dizziness or 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 VIMPAT® on their ability to perform such activities. Undesirable effects: The most common adverse reactions (≥10%) are dizziness, headache, diplopia, and nausea. They were usually mild to moderate in intensity. Some were dose-related and could be alleviated by reducing the dose. Incidence and severity of CNS and gastrointestinal (GI) adverse reactions usually decreased over time. Incidence of CNS adverse reactions such as dizziness may be higher after a loading dose. 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, paraesthesia, vision blurred, vertigo, tinnitus, vomiting, constipation, flatulence, dyspepsia, dry mouth, diarrhoea, pruritus, rash, muscle spasms, gait disturbance, asthenia, fatigue, irritability, feeling drunk, injection site pain or discomfort (local adverse events associated with intravenous administration), irritation (local adverse events associated with intravenous administration), fall, and skin laceration, contusion. The use of VIMPAT® is associated with dose-related increase in the PR interval. Adverse reactions associated with PR interval prolongation (e.g. atrioventricular block, syncope, bradycardia) may occur. Laboratory abnormalities: Abnormalities in liver function tests have been observed in controlled trials with VIMPAT® 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 VIMPAT® patients and 0% (0/356) of placebo patients. Multiorgan Hypersensitivity Reactions: Multiorgan hypersensitivity reactions (also known as Drug Reaction with Eosinophilia and Systemic Symptoms, DRESS) 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. If multiorgan hypersensitivity reaction is suspected, VIMPAT® should be discontinued.