Eisai Receives CHMP Positive Opinion for Fycompa® Pediatric Indication in Europe
European Medicines Agency
The European Medicines Agency (EMA) is a decentralized agency of the European Union (EU), located in London. It began operations in 1995. The agency is responsible for the scientific evaluation, supervision, and safety monitoring of medicines developed by pharmaceutical companies for use in the EU. By ensuring that all medicines available on the EU market are safe, effective, and of high quality, the EMA protects public and animal health in the 28 EU Member States and countries of the European Economic Area.
Committee for Medicinal Products for Human Use
Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.
Eisai
Pharmaceutical Product R&D and Manufacturer
TOKYO, Oct. 7, 2020 /PRNewswire/ -- Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) announced that the application for an extension of the marketing authorization for the pediatric indication of its exclusively developed anti-epileptic drug (AED) Fycompa® (generic name: perampanel), submitted by its UK subsidiary, has received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA). The CHMP’s positive opinion supports expanding the use of Fycompa as an adjunctive therapy for partial-onset seizures (POS) (with or without secondary generalization) by extending the approved age range from 12 years and older to 4 years and older, and by extending the age range for primary generalized tonic-clonic seizures (PGTCS) from 12 years and older to 7 years and older.
This application (submitted to the EMA in February 2019) is based on the results of global Phase III (Study 311) and Phase II (Study 232) clinical studies. These studies evaluated Fycompa as adjunctive therapy for pediatric patients with POS or PGTCS. Study 311 assessed the safety, tolerability, and exposure-efficacy relationship of Fycompa as adjunctive therapy in pediatric patients aged 4 to <12 years with inadequately controlled POS or PGTCS. Study 232 evaluated the pharmacokinetics, efficacy, and long-term safety of Fycompa as adjunctive therapy in pediatric epilepsy patients aged 2 to <12 years.
Fycompa is a novel antiepileptic drug exclusively developed by Eisai. Seizures are mediated by the neurotransmitter glutamate. This medication is a highly selective, non-competitive AMPA receptor antagonist that reduces neuronal hyperexcitability associated with seizures by targeting glutamate activity at AMPA receptors on the postsynaptic cell membrane. In Japan, Fycompa is indicated as monotherapy and adjunctive therapy for patients aged 4 years and older with partial-onset seizures (with or without secondary generalization), and as adjunctive therapy for primary generalized tonic-clonic seizures in patients aged 12 years and older. Furthermore, in the United States, Fycompa is also indicated as monotherapy and adjunctive therapy for patients aged 4 years and older with partial-onset seizures (with or without secondary generalization), and as adjunctive therapy for primary generalized tonic-clonic seizures in patients aged 12 years and older.
Eisai considers neurology, including epilepsy, a key therapeutic area. With the launch of Fycompa in Europe, Eisai is committed to helping more patients with epilepsy around the world achieve the goal of “zero seizures.” Eisai is dedicated to meeting the diverse needs of patients with epilepsy and their families, providing them with greater benefits.
[Editor's Note]
1. AboutFycompa(Generic Name: Perampanel)
Fycompa is a novel antiepileptic drug exclusively developed by Eisai. Seizures are mediated by the neurotransmitter glutamate. As a highly selective, non-competitive AMPA receptor antagonist, Fycompa reduces the hyperexcitability of neurons associated with seizures by targeting glutamate activity at AMPA receptors on the postsynaptic membrane. Fycompa formulations are currently marketed for once-daily oral administration at bedtime. Tablet and fine granule formulations have been approved in Japan. The oral suspension and tablet formulations have been approved in the United States and Europe.
Currently, Fycompa is approved as an adjunctive therapy for partial-onset seizures (with or without secondary generalization) in patients aged 12 years and older with epilepsy in more than 70 countries and regions, including Japan, the United States, China, and other countries in Europe and Asia. Furthermore, Fycompa has been approved in more than 65 countries, including the United States, Japan, and nations across Europe and Asia, as an adjunctive therapy for primary generalized tonic-clonic seizures in patients aged 12 years and older with epilepsy. In Japan and the United States, Fycompa is approved for both monotherapy and adjunctive therapy for partial-onset seizures (with or without secondary generalization) in patients aged 4 years and older with epilepsy. To date, Fycompa has been widely used to treat more than 300,000 patients worldwide (across all indications combined). Eisai is currently conducting a global Phase III clinical study (Study 338) to evaluate the use of this drug for the treatment of seizures associated with Lennox-Gastaut syndrome. Additionally, the development of an injectable formulation of Fycompa by Eisai is underway.
2. About the Study 3111
Study 311 is a global (United States, Europe, Japan, South Korea) open-label Phase III clinical study evaluating the safety, tolerability, and exposure-efficacy relationship of Fycompa oral suspension as adjunctive therapy in 180 pediatric patients aged 4 to <12 years with inadequately controlled partial-onset seizures or primary generalized tonic-clonic seizures. The study comprises a treatment period (including a titration phase of up to 11 weeks and a maintenance phase of up to 12 weeks) and an extension period. In this study, Fycompa was administered orally once daily at bedtime at doses ranging from 2 to 16 mg. The primary endpoints were safety and tolerability. Efficacy was similar to that observed in patients aged 12 years and older. The most commonly observed adverse events (incidence ≥10%) in this study were somnolence, nasopharyngitis, pyrexia, vomiting, dizziness, influenza, and irritability, which are consistent with the safety profile of Fycompa established to date.
3. About the Study 2322
Study 232 was a global (United States, Europe), multicenter, open-label clinical study with an extension phase, designed to evaluate Fycompa oral suspension in 63 pediatric patients with epilepsy (aged 2 years to less than 12 years). The study assessed the pharmacokinetics, safety, tolerability, and efficacy of Fycompa oral suspension administered concomitantly with other antiepileptic drugs (AEDs). Fycompa was titrated once daily within a dose range of 0.015 mg/kg to 0.18 mg/kg. Long-term safety was confirmed after 11 weeks of treatment plus a 41-week extension period. Adverse events observed in Study 232 (occurring in ≥10% of patients in the Fycompa group) included pyrexia, fatigue, vomiting, irritability, somnolence, dizziness, and upper respiratory tract infection.
4. About Epilepsy
Epilepsy is broadly classified by seizure type. Focal seizures account for approximately 60% of epilepsy cases, while generalized seizures account for approximately 40%. In focal seizures, abnormal electrical discharges originate in a limited area of the brain and may subsequently spread to the entire brain, evolving into generalized seizures (termed secondary generalized seizures). In generalized seizures, abnormal electrical discharges involve the entire brain from the onset, often resulting in loss of consciousness or systemic physical symptoms.
Epilepsy affects approximately 1 million people in Japan, 3.4 million in the United States, 6 million in Europe, 9 million in China, and around 60 million people worldwide.
As approximately 30% of patients with epilepsy are unable to achieve seizure control with existing antiepileptic drugs (AEDs), this condition represents an area of significant unmet medical need. Although seizures can occur at any age, they are most prevalent in individuals aged 18 years or younger and in the elderly. Due to the heterogeneous etiologies and clinical manifestations of pediatric epilepsy, along with a prognosis that ranges from highly favorable to refractory, treatment strategies require careful individualization for each patient.
1A. Fogarasi et al. Open-label study—aimed at investigating the adjunctive therapy drug perampanel for focal seizures or generalized tonic-clonic seizures in children (aged 4 to <12 years)EpilepsySafety and efficacy of seizures. January 2020; Vol. 61(1): pp. 125-137.
2J. Ben Renfroe et al. Adjunctive Perampanel Oral Suspension in Pediatric Patients with Epilepsy Aged ≥2 to <12 Years: Pharmacokinetics, Safety, Tolerability, and Efficacy. J Child Neurol. 2019 Apr;34(5):284-294.
3"Epilepsy and Seizures: Hope Through Research. What Is Epilepsy?" National Institute of Neurological Disorders and Stroke, accessed May 24, 2016,http://www.ninds.nih.gov/disorders/epilepsy/detail_epilepsy.htm#230253109