- Source : Press Release
- Date : 2022-02-02
- Event type : Registration
- Companies : UCB Pharma S.A.
UCB Receives Positive CHMP Opinion Recommending Approval of BRIVIACT (Brivaracetam) and VIMPAT (Lacosamide) in the EU for Partial-Onset Seizures in Pediatric Patients from Two to Four Years
- The CHMP has recommended approval of BRIVIACT® (brivaracetam) for use as adjunctive therapy for the treatment of partial-onset seizures (POS) with or without secondary generalization in patients from two to four years of age
- CHMP has also recommended approval of VIMPAT® (lacosamide) for use as both monotherapy and adjunctive therapy for the treatment of POS with or without secondary generalization in patients from two to four years of age
- The positive CHMP opinions are based on extrapolation of efficacy data from adolescents and adults and supported by safety and pharmacokinetics data in children including open label follow-up pediatric studies which assessed long-term safety for patients under 16 years with POS with or without secondary generalization1,2
- With these positive CHMP opinions, BRIVIACT® (brivaracetam) and VIMPAT® (lacosamide) will provide young patients and their caregivers with additional treatment options for POS with or without secondary generalization
Brussels (Belgium) 02 February 2022 – 07:00 (CET): – UCB, a global biopharmaceutical company, announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended approval of a label extension for BRIVIACT® (brivaracetam) and Vimpat® (lacosamide) to treat partial onset seizures with or without secondary generalization in patients from two to four years of age.3,4
“These positive CHMP opinions are significant milestones for children living with epilepsy in Europe. We are delighted by today’s opinions which take us a step closer towards reducing the number of partial-onset seizures these young and vulnerable people experience.” said Alexandre Moreau, Global Head of Epilepsy and Vice President at UCB. “At UCB, we are driven to improve the lives of people living with epilepsy by addressing the unpredictable nature of seizures and the potentially profound consequences they can have on pediatric patients.”
Childhood epilepsy varies in severity and prognosis and may have profound consequences on development and functioning.5,6 Seizure burden can impair cognition with effects being most severe in infancy.6,7 Despite these elevated challenges, few antiseizure medications are approved for treating partial-onset seizures in this vulnerable patient population.
The positive CHMP opinions are based on the extrapolation of data demonstrating the safety and efficacy of brivaracetam and lacosamide in a pediatric population (from two to four years of age). This principle of extrapolating clinical data from well controlled studies has been recognized by EMA as potentially addressing the challenge of limited pediatric data availability. As a result, antiseizure medications which have previously been approved for treating adults with epilepsy, are becoming available to pediatric epilepsy patients. UCB has embraced these guidelines, addressing a significant need for this poorly served patient population.
Brivaracetam and lacosamide data in pediatric patients include long-term exposure for more than 2 years. In an open label follow-up pediatric study, an estimated 70.4% and 57.7% of patients, aged 1 month to 16 years* with partial-onset seizures (n=189), remained on treatment with brivaracetam at 1 and 2 years, respectively.1 Meanwhile, in a separate open label follow-up pediatric study for lacosamide, an estimated 73.6% and 47.7% of patients, aged 1 month to 16 years* with partial-onset seizures (n=822), remained on treatment with brivaracetam at 1 and 2 years, respectively.2
At UCB, our commitment to the epilepsy community has never been stronger. Our goal is about what’s good for society and people living with epilepsy and we are dedicated in finding new ways to provide the most value for all people living with epilepsy.
* The full clinical data submitted by UCB include data from a pediatric population aged from 1 month to 16 years. EMA accepted to extrapolate from the age of 2 years.
Epilepsy is a common neurological condition worldwide and affects approximately 50 million people.8 Epilepsy and seizures can develop in any person at any age,9 and is usually diagnosed after a person has had at least two seizures (or after one seizure with a high risk for more) that were not caused by some known medical condition.10
About UCB in Epilepsy
UCB has a rich heritage in epilepsy with over 20 years of experience in the research and development of antiepileptic 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 8 000 people operating in more than 40 countries, the company generated revenue of €5.3 billion in 2020. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCB_news
About BRIVIACT® (brivaracetam)
Important Safety Information about BRIVIACT® in the EU and EEA11
BRIVIACT® (brivaracetam) is indicated as adjunctive therapy in the treatment of partial-onset seizures with or without secondary generalization in adults, adolescents, and children from 4 years of age with epilepsy. Contraindications Hypersensitivity to the active substance, other pyrrolidone derivatives or any of the excipients. Special warnings and precautions for use Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic drugs (AEDs) in several indications, including BRIVIACT®. Patients should be monitored for signs of suicidal ideation and behaviour and appropriate treatment should be considered. Patients (and caregivers) should be advised to seek medical advice should any signs of suicidal ideation or behaviour emerge. BRIVIACT® film-coated tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take BRIVIACT®. Brivaracetam film-coated tablets, solution for injection/infusion and oral solution contain less than 1 mmol sodium (23mg) per tablet/vial/ml respectively, that is to say essentially ‘sodium free’. The oral solution contains 239.8 mg sorbitol (E420) in each ml. Patients with hereditary fructose intolerance (HFI) should not take this medicinal product. The oral solution contains methyl parahydroxybenzoate (E218), which may cause allergic reactions (possibly delayed). Brivaracetam oral solution contains propylene glycol (E1520). Posology No dose adjustment is needed in adults with impaired renal function. Based on data in adults, no dose adjustment is necessary neither in paediatric patients with impaired renal function. In adults with hepatic impairment, a 50 mg/day starting dose should be considered. In children and adolescents weighing 50 kg or greater, a 50 mg/day starting dose is recommended. A maximum daily dose of 150 mg administered in 2 divided doses is recommended for all stages of hepatic impairment. In children and adolescents weighing less than 50 kg, a 1 mg/kg/day starting dose is recommended. The maximum dose should not exceed 3 mg/kg/day. No clinical data are available in paediatric patients with hepatic impairment. Interaction with other medicinal products and other forms of interaction. With co-administration of BRIVIACT® 200 mg single dose and ethanol 0.6 g/L continuous infusion in healthy subjects there was no pharmacokinetic interaction, but the effect of alcohol on psychomotor function, attention and memory was doubled. Intake of BRIVIACT® with alcohol is not recommended. Limited clinical data are available implying that coadministration of cannabidiol may increase the plasma exposure of brivaracetam, possibly through CYP2C19 inhibition, but the clinical relevance is uncertain. In healthy subjects, co-administration with rifampicin, a strong enzyme-inducer (600 mg/day for 5 days), decreased BRIVIACT® area under the plasma concentration curve (AUC) by 45%. Prescribers should consider adjusting the dose of BRIVIACT® for patients starting or ending treatment with rifampicin. Other strong enzyme-inducers (such as St John´s wort [Hypericum perforatum]) may also decrease the systemic exposure of BRIVIACT®. Therefore, starting or ending treatment with St John’s wort should be done with caution. In vitro studies have shown that brivaracetam exhibits little or no inhibition of CYP450 isoforms except for CYP2C19. Brivaracetam may increase plasma concentrations of medicinal products metabolised by CYP2C19 (e.g., lansoprazole, omeprazole, diazepam). CYP2B6 induction has not been investigated in vivo and BRIVIACT® may decrease plasma concentrations of medicinal products metabolised by CYP2B6 (e.g. efavirenz). In vitro studies have also shown that BRIVIACT® has inhibitory effects on OAT3. BRIVIACT® 200 mg/day may increase plasma concentrations of medicinal products transported by OAT3. BRIVIACT® plasma concentrations are decreased when co-administered with strong enzyme inducing antiepileptic drugs (carbamazepine, phenobarbital, phenytoin) but no dose adjustment is required. Effects on ability to drive and use machines BRIVIACT®, has minor or moderate influence on the ability to drive and use machines. Patients should be advised not to drive a car or to operate other potentially hazardous machines until they are familiar with the effects of BRIVIACT®, on their ability to perform such activities. Undesirable effects. The most frequently reported adverse reactions with BRIVIACT® (reported by >10% of patients) were somnolence (14.3%) and dizziness (11.0%). They were usually mild to moderate in intensity. Somnolence and fatigue (8.2 %) were reported at higher incidences with increasing dose. Very common adverse reactions (≥1% to <10%) were influenza, decreased appetite, depression, anxiety, insomnia, irritability, convulsion, vertigo, upper respiratory tract infections, cough, nausea, vomiting, constipation and fatigue. Neutropenia has been reported in 0.5% (6/1,099) BRIVIACT® patients and 0% (0/459) placebo-treated patients. Four of these patients had decreased neutrophil counts at baseline, and experienced additional decrease in neutrophil counts after initiation of BRIVIACT®. None of the six cases were severe, required any specific treatment, led to BRIVIACT® discontinuation or had associated infections. Suicidal ideation was reported in 0.3 % (3/1099) of BRIVIACT® treated patients and 0.7 % (3/459) of placebo-treated patients. In short-term clinical studies of BRIVIACT® in patients with epilepsy, there were no cases of completed suicide and suicide attempt, however both were reported in the long-term open-label extension studies. Reactions suggestive of immediate (Type I) hypersensitivity have been reported in a small number of BRIVIACT® patients (9/3022) during clinical development. The safety profile of brivaracetam observed in children was consistent with the safety profile observed in adults. In the open label, uncontrolled, long-term studies suicidal ideation was reported in 4.7 % of paediatric patients (more common in adolescents) compared with 2.4 % of adults and behavioural disorders were reported in 24.8 % of paediatric patients compared with 15.1 % of adults. The majority of events were mild or moderate in intensity, were non-serious, and did not lead to discontinuation of study drug. An additional adverse reaction reported in children was psychomotor hyperactivity (4.7 %). There are limited safety data from open-label studies in children from 1 month to <4 years of age. Limited data are available on neurodevelopment in children <4 years of age. No clinical data are available in neonates. Overdose There is limited clinical experience with BRIVIACT® overdose in humans. Somnolence and dizziness were reported in a healthy subject taking a single dose of 1,400 mg of BRIVIACT®. The following adverse reactions were reported with brivaracetam overdose: nausea, vertigo, balance disorder, anxiety, fatigue, irritability, aggression, insomnia, depression, and suicidal ideation in the post-marketing experience. In general, the adverse reactions associated with brivaracetam overdose were consistent with the known adverse reactions. There is no specific antidote. Treatment of an overdose should include general supportive measures. Since less than 10% of BRIVIACT® is excreted in urine, haemodialysis is not expected to significantly enhance BRIVIACT® clearance.
Refer to the European Summary of Product Characteristics for other adverse reactions and full prescribing information. Date of revision: 22 November 2021
About VIMPAT® (lacosamide)
Important Safety Information about VIMPAT® in the EU and EEA12
VIMPAT® is indicated as monotherapy in the treatment of partial-onset seizures with or without secondary generalisation in adults, adolescents and children from 4 years of age with epilepsy. VIMPAT® is indicated as adjunctive therapy in the treatment of partial-onset seizures with or without secondary generalisation in adults, adolescents and children from 4 years of age with epilepsy and in the treatment of primary generalised tonic-clonic seizures in adults, adolescents and children from 4 years of age with idiopathic generalised epilepsy. VIMPAT® therapy can be initiated with either oral or IV administration. For the paediatric population, the physician should prescribe the most appropriate formulation and strength according to weight and dose. 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 serious cardiac arrhythmia and CNS adverse reactions. Administration of a loading dose has not been studied in acute conditions such as status epilepticus. Use of a loading dose is not recommended in adolescents and children weighing less than 50 kg. Administration of a loading dose has not been studied in children. A maximum dose of 300 mg/day is recommended for paediatric patients weighing 50 kg or more and for adult patients with mild to moderate hepatic impairment. Based on data in adults, in paediatric patients weighing less than 50 kg with mild to moderate hepatic impairment, a reduction of 25 % of the maximum dose should be applied. Lacosamide should be administered to adult and paediatric patients with severe hepatic impairment only when the expected therapeutic benefits are anticipated to outweigh the possible risks. The dose may need to be adjusted while carefully observing disease activity and potential side effects in the patient. In adolescents and adults weighing 50 kg or more with mild to moderate hepatic impairment a loading dose of 200mg may be considered, but further dose titration (>200 mg daily) should be performed with caution. In paediatric patients weighing 50 kg or more and in adult patients with mild or moderate renal impairment a loading dose of 200 mg may be considered, but further dose titration (> 200 mg daily) should be performed with caution. In paediatric patients weighing 50 kg or more and in adult patients with severe renal impairment (CLCR ≤ 30 ml/min) or with end-stage renal disease, a maximum dose of 250 mg/day is recommended and the dose titration should be performed with caution. In paediatric patients weighing less than 50 kg with severe renal impairment (CLCR ≤ 30 ml/min) and in those with end-stage renal disease, a reduction of 25 % of the maximum dose is recommended. 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. New onset or worsening of myoclonic seizures has been reported in both adult and paediatric patients with PGTCS, in particular during titration. In patients with more than one seizure type, the observed benefit of control for one seizure type should be weighed against any observed worsening in another seizure type. Dose-related prolongations in PR interval with VIMPAT® have been observed in clinical studies. VIMPAT® should be used with caution in patients with underlying proarrhythmic conditions such as patients with known cardiac conduction problems or severe cardiac disease (e.g. myocardial ischaemia/infarction, heart failure, structural heart disease or cardiac sodium channelopathies) or patients treated with medicinal products affecting cardiac conduction, including antiarrhythmics and sodium channel blocking antiepileptic medicinal products, as well as in elderly patients. In these patients it should be considered to perform an ECG before a Vimpat dose increase above 400mg/day and after Vimpat is titrated to steady-state. In the placebo-controlled studies of VIMPAT® in epilepsy patients, atrial fibrillation or flutter were not reported; however both have been reported in open-label epilepsy studies and in post-marketing experience. In post-marketing experience, AV block (including second degree or higher AV block) has been reported. In patients with proarrhythmic conditions, ventricular tachyarrhythmia has been reported. In rare cases, these events have led to asystole, cardiac arrest and death in patients with underlying proarrhythmic conditions. Patients should be made aware of the symptoms of cardiac arrhythmia (e.g. slow, rapid or irregular pulse, palpitations, shortness of breath, feeling lightheaded, fainting). Patients should be counselled to seek immediate medical advice if these symptoms occur. Suicidal ideation and behaviour have been reported in patients treated with antiepileptic medicinal products 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. The safety and efficacy of lacosamide in paediatric patients with epilepsy syndromes in which focal and generalised seizures may coexist have not been determined. VIMPAT® syrup contains sodium methyl parahydroxybenzoate (E219) which may cause allergic reactions (possibly delayed). Vimpat Syrup contains sorbitol (E420). Patients with rare hereditary problems of fructose intolerance should not take this medicine. Sorbitol may cause gastrointestinal discomfort and mild laxative effect. The syrup contains aspartame (E951), a source of phenylalanine, which may be harmful for people with phenylketonuria. Vimpat syrup contains propylene glycol (E1520). VIMPAT® syrup contains 1.42 mg sodium per ml, equivalent to 0.07 % of the WHO recommended maximum daily intake of 2 g sodium for an adult. VIMPAT® solution for infusion contains 59.8 mg sodium per vial, equivalent to 3% of the WHO recommended maximum daily intake of 2 g sodium for an adult. 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, myoclonic seizures, ataxia, 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. Additional adverse reactions reported in PGTCS patients were myoclonic epilepsy and ataxia. The most frequently reported adverse reactions were dizziness and somnolence. The most common adverse reactions resulting in discontinuation of lacosamide therapy were dizziness and suicidal ideation. The safety profile of lacosamide in placebo-controlled and in open-label studies (n=408) in adjunctive therapy in children from 4 years of age with partial- onset seizures was consistent with the safety profile observed in adults although the frequency of some adverse reactions (somnolence, vomiting and convulsion) was increased and additional adverse reactions (nasopharyngitis, pyrexia, pharyngitis, decreased appetite, lethargy and abnormal behaviour) have been reported in paediatric patients: nasopharyngitis (15.7 %), vomiting (14.7 %), somnolence (14.0 %), dizziness (13.5 %), pyrexia (13.0 %), convulsion (7.8 %), decreased appetite (5.9 %), pharyngitis (4.7 %), lethargy (2.7 %) and abnormal behaviour (1.7 %).
Laboratory abnormalities: Abnormalities in liver function tests have been observed in placebo-controlled studies with VIMPAT® in adult patients with partial-onset seizures who were taking 1-3 concomitant antiepileptic medicinal products. 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 medicinal products. 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.
Refer to the European Summary of Product Characteristics for other adverse reactions and full prescribing information. Date of revision: 10 June 2021. http://www.ema.europa.eu/
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