WOODCLIFF LAKE, N.J., Dec. 7, 2020 /PRNewswire/ -- Eisai Inc. presented 52-week seizure freedom data related to its antiepileptic drug (AED) FYCOMPA® (perampanel) CIII at the 2020 American Epilepsy Society (AES) Annual Meeting virtual conference. In a post-hoc analysis of the Phase III FREEDOM study, seizure freedom rates were observed across patients with newly diagnosed or untreated POS with or without secondarily generalized seizures (SGS). Of the 32 patients who entered the 4 mg/day Extension Phase and were included in the Extension mITT Analysis Set, the sustained seizure freedom rate was 62.5% (n=20/32) in patients at 52 weeks with FYCOMPA.

Four (23.5%) patients had no seizures but discontinued due to other reasons and 13 (76.5%) experienced ≥ 1 of the following seizure types, so entered the 8 mg/day Treatment Phase: SGS, n=6 (35.3%); complex partial seizures (CPS), n=5 (29.4%); simple POS with/without motor signs, n=1 (5.9%) each. TEAEs (treatment-emergent adverse events) occurred in 72 (80.9%) patients in the Safety Analysis Set (N=89) across the Core and Extension Phase; most common were dizziness (36.0%), nasopharyngitis (19.1%), somnolence (13.5%), headache (12.4%) and seizures (6.7%).

Data was also presented from a real-world analysis of 430 patients treated with FYCOMPA as early add- on therapy for focal or generalized seizures from 18 studies/work groups. Effectiveness assessments comprised seizure freedom rate, responder rate, and the proportion of patients with unchanged or worsening seizure frequency. At the last visit, seizure freedom rates in patients with focal and generalized seizures were 34.8% (n=125/359) and 56.1% (n=32/57), respectively, and corresponding values for responder rates were 80.2% and 80.7%, respectively.

AEs were reported in 40.9% (n=174/425) of patients with the most frequently reported AEs as behavioral AEs (aggression/anger/irritability; 15.1%), somnolence (12.9%) and dizziness/vertigo (10.6%).

"Analyses of real-world data help complement clinical trial evidence by providing information about epilepsy patients with more diverse characteristics than patients typically recruited in trials," said Manoj Malhotra, Vice President, Head of Medical Affairs for the Neurology Business Group at Eisai Inc. and the lead study investigator. "Results from these real-world analyses show the potential of FYCOMPA as a monotherapy and as a first add-on for patients with Partial-Onset Seizures in a routine clinical setting."

"It is exciting to see Eisai's human health care mission and commitment to patients, families, and healthcare professionals brought to life with the breadth and depth of research presented at the 2020 American Epilepsy Society Meeting. With 50 presentations, our commitment to the epilepsy community has never been stronger. We are sharing new findings that reflect the diverse set of epilepsy patients with different seizure types that have been studied in the early use of FYCOMPA," said Ivan Cheung, Chairman, Eisai Inc. and Global President, Neurology Business Group, Eisai Co., Ltd. "We are also excited to share the latest update from the FREEDOM study that evaluated the long-term use of FYCOMPA as monotherapy in patients with partial-onset seizures. The results are encouraging as we continue to work toward the goal of seizure freedom for patients taking antiepileptic drug therapy."  

Key data presented:

Poster presentation number: 556
Poster session: Three
Sunday, December 6, 5:15 p.m. to 6:45 p.m. EST

Sustained Seizure Freedom with Perampanel 4 mg/day Monotherapy in Patients with Newly Diagnosed/Currently Untreated Recurrent Partial-Onset Seizures: Post Hoc Analysis of Study 342 (FREEDOM)

Summary: The interim pooled analysis of FREEDOM extension phase, which was a multicenter, uncontrolled, open-label, single-arm, Phase III study of FYCOMPA monotherapy in patients aged 12–74 years with POS, with or without SGS, comprised 4 and 8 mg/day treatment phases. Patients received FYCOMPA 4 mg/day (4-week Pretreatment; 32-week Treatment [6-week Titration; 26-week Maintenance]), with titration up to 8 mg/day (4-week Titration; 26-week Maintenance) in case of seizure. Patients completing the Core Study could enter an Extension Phase. Seizure-freedom rates, defined at 52 weeks (Core and Extension Phases), at 4 mg/day for POS and based on seizure history were assessed in patients who were seizure free during the 4 mg/day Core Study Maintenance Period (calculated from the start of their seizure-free period). Treatment-emergent adverse events (TEAEs) were monitored.

Seizure-freedom rates for 26 weeks were 63.0% (n=46/73) in patients with POS during the 4 mg/day Maintenance Period. The seizure freedom rate was 62.5% in the mITT population (n=20/32) at 4 mg/day for 52 weeks. Seizure freedom was sustained for 52 weeks at 4 mg/day in 63.2% of patients (n=12/19) in the mITT who reported history of complex partial seizures (CPS), 61.3% of patients (n=19/31) with history of CPS and/or SGS, and 57.1% of patients (n=12/21) with history of SGS. Four (23.5%) patients had no seizures but discontinued due to other reasons and 13 (76.5%) experienced ≥ 1 of the following seizure types so entered the 8 mg/day Treatment Phase: SGS, n=6 (35.3%); CPS, n=5 (29.4%); simple POS with/without motor signs, n=1 (5.9%) each. TEAEs occurred in 72 (80.9%) patients in the SAS across the Core and Extension Phase; most common were dizziness (36.0%), nasopharyngitis (19.1%), and somnolence (13.5%), followed by headache (12.4%) and seizures (6.7%).

Poster presentation number: 523
Poster session: Three
Sunday, December 6, 5:15 p.m. to 6:45 p.m. EST

Perampanel Monotherapy in Epilepsy Patients with Focal and Generalized Seizures: Real-World Experience

Summary: This pooled analysis included data from 111 epilepsy patients treated with FYCOMPA as monotherapy for focal or generalized seizures identified from 18 retrospective, prospective and cross- sectional real-world studies/work groups worldwide. Subjects included both patients treated with first-line FYCOMPA monotherapy and those who converted to FYCOMPA monotherapy from a single antiseizure medication (ASM). Overall, mean duration of epilepsy was 14.3 years, and mean number of previous ASMs was 4.0. Seizure types at baseline included focal only (54.7%), generalized only (42.2%), and both focal and generalized (3.1%). At the last visit, seizure freedom rates in patients with focal and generalized seizures were 20.0% and 47.6%, respectively, and corresponding values for responder rates were 50.0% and 100%. TEAEs were reported in 60.5% (n=23/38) of patients, the most common being behavioral AES (aggression/anger/irritability; 26.3%), dizziness/vertigo (21.1%), depressed mood/mood disturbances (7.9%), anxiety, nausea/vomiting/gastrointestinal problems and somnolence (5.3% each). Overall, 44.4% (8/18) of patients discontinued FYCOMPA treatment. Two patients discontinued FYCOMPA due to AEs, one of whom discontinued due to a psychiatric AE, and 5.6% of patients discontinued due to worsening seizures.

Data were pooled for baseline number of seizures, type of epilepsy/seizures, prior ASMs, dosage, effectiveness at various time points, and adverse events (AEs). Patient's retention rates were assessed after 3, 6 and 12 months of FYCOMPA treatment. At 3, 6 and 12 months, overall retention rates were 94.4% (17/18), 88.9% (16/18) and 55.6% (10/18), respectively. Mean (95% confidence interval) time under FYCOMPA treatment was 9.5 (7.8-11.2) months. Effectiveness of FYCOMPA monotherapy was assessed by seizure type (focal or generalized) at the last visit (i.e., the last observation of each patient, independent of the timepoint when it occurred). Effectiveness assessments comprised seizure freedom rate (defined as no seizures since at least the prior visit), responder rate (defined as ≥50% seizure frequency reduction from baseline), and the proportion of patients with unchanged or worsening seizure frequency.

Poster presentation number: 302
Poster session: Two
Monday, December 6, 12:00 p.m. to 1:30 p.m. EST

Perampanel as Early Add-on Therapy for Epilepsy Patients with Focal and Generalized Seizures Treated in Clinical Practice

Summary: Patients treated with FYCOMPA as early add-on therapy for focal or generalized seizures were identified from an interim pooled analysis of 18 retrospective, prospective and cross-sectional real-world studies/work groups (a total of 430 patients) from a range of countries. Retention was assessed after 3, 6 and 12 months of FYCOMPA treatment. Effectiveness was assessed by seizure type (focal or generalized) at the last visit (i.e., the last observation of each patient, independent of the timepoint when it occurred). Effectiveness assessments comprised seizure freedom rate (seizure freedom defined as no seizures since at least the prior visit, i.e., either 3 or 6 months), responder rate (response defined as ≥50% seizure frequency reduction from baseline) and the proportions of patients with unchanged or worsening seizure frequency. Seizure types at baseline were focal only (85.0%), generalized only (14.3%), and both focal and generalized (0.7%).

At treatment initiation, the majority of patients (N=430) were receiving one (61.0%) or two (27.6%) concomitant ASMs. Mean (SD) FYCOMPA dosage was 3.3 (1.7) mg/day at initiation and 5.7 (2.2) mg/day at the last visit. At 3, 6 and 12 months, overall retention rates were 94.4% (n=401/425), 86.1% (n=366/425) and 79.3% (n=333/420), respectively. Mean (95% confidence interval) time under FYCOMPA treatment was 12.0 (11.6–12.4) months. At the last visit, seizure freedom rates in patients with focal and generalized seizures were 34.8% and 56.1%, respectively, and corresponding values for responder rates were 80.2% and 80.7%, respectively. Worsening seizure frequency was experienced by 0.3% and 1.8% of patients with focal and generalized seizures, respectively. AEs were reported for 40.9% (n=174/425) of patients with the most frequently reported AEs as behavioral AEs (aggression/anger/irritability; 15.1%), somnolence (12.9%) and dizziness/vertigo (10.6%). Psychiatric AEs were reported for 19.3% (n=82/425) of patients. Thirty-three patients (7.8%) discontinued due to psychiatric AEs. Behavioral AEs were the most common type of psychiatric AEs leading to discontinuation (6.8%).

INDICATION FOR FYCOMPA
FYCOMPA® (perampanel) is indicated in patients with epilepsy aged 4 years and older for partial-onset seizures (POS) with or without secondarily generalized seizures and adjunctive therapy for patients aged 12 years and older for primary generalized tonic-clonic (PGTC) seizures.

IMPORTANT SAFETY INFORMATION FOR FYCOMPA

SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS
In the partial-onset seizures clinical trials, hostility- and aggression-related adverse reactions occurred in 12% and 20% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 6% of patients in the placebo group. These effects were dose-related and generally appeared within the first 6 weeks of treatment, although new events continued to be observed through more than 37 weeks. These effects in FYCOMPA-treated patients led to dose reduction, interruption, and discontinuation more frequently than placebo-treated patients. Homicidal ideation and/or threat have also been reported postmarketing in patients treated with FYCOMPA. The combination of alcohol and FYCOMPA significantly worsened mood and increased anger. Patients taking FYCOMPA should avoid the use of alcohol. Patients, their caregivers, and families should be informed that FYCOMPA may increase the risk of psychiatric events. Patients should be monitored during treatment and for at least one month after the last dose of FYCOMPA, and especially when taking higher doses and during the initial few weeks of drug therapy (titration period) or at other times of dose increases. Similar serious psychiatric and behavioral events were observed in the primary generalized tonic-clonic (PGTC) seizure clinical trial.

SUICIDAL BEHAVIOR AND IDEATION
Antiepileptic drugs (AEDs), including FYCOMPA, increase the risk of suicidal thoughts or behavior in patients. Anyone considering prescribing FYCOMPA or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, their caregivers, and families should be informed of the risk and advised to monitor and immediately report the emergence or worsening of depression, suicidal thoughts or behavior, thoughts about self-harm and/or any unusual changes in mood or behavior. Should suicidal thoughts and behavior emerge during treatment, consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

DIZZINESS AND GAIT DISTURBANCE
FYCOMPA caused dose-related increases in events related to dizziness and disturbance in gait or coordination. Dizziness and vertigo were reported in 35 (and 47% of patients in the partial-onset seizure trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 10% of placebo-treated patients. Gait disturbance related events were reported in 12% and 16% of patients in the partial-onset seizure clinical trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 2% of placebo-treated patients. These adverse reactions occurred mostly during the titration phase. These adverse reactions were also observed in the PGTC seizure clinical trial.

SOMNOLENCE AND FATIGUE
FYCOMPA caused dose-dependent increases in somnolence and fatigue-related events. Somnolence was reported in 16% and 18% of patients in the partial-onset seizure trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 7% of placebo-treated patients. Fatigue-related events were reported in 12% and 15% of patients in the partial-onset seizure trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 5% of placebo-treated patients. These adverse reactions occurred mostly during the titration phase. These adverse reactions were also observed in the PGTC seizure clinical trial. Patients should be advised against engaging in hazardous activities requiring mental alertness, such as operating motor vehicles or dangerous machinery, until the effect of FYCOMPA is known. Patients should be carefully observed for signs of central nervous system (CNS) depression when FYCOMPA is used with other drugs with sedative properties because of potential additive effects.

FALLS
Falls were reported in 5% and 10% of patients in the partial-onset seizure clinical trials randomized to receive FYCOMPA at doses of 8 mg and 12 mg per day, respectively, compared to 3% of placebo-treated patients.

DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS)
DRESS, also known as multiorgan hypersensitivity, has been reported in patients taking AEDs, including FYCOMPA. DRESS may be fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement. If signs or symptoms are present, immediately evaluate the patient and discontinue FYCOMPA if an alternative etiology for signs or symptoms cannot be established.

WITHDRAWAL OF AEDs
A gradual withdrawal is generally recommended with AEDs to minimize the potential of increased seizure frequency, but if withdrawal is a response to adverse events, prompt withdrawal can be considered.

MOST COMMON ADVERSE REACTIONS
The most common adverse reactions in patients aged 12 years and older receiving FYCOMPA (≥5% and ≥1% higher than placebo) include dizziness, somnolence, fatigue, irritability, falls, nausea, weight gain, vertigo, ataxia, headache, vomiting, contusion, abdominal pain, and anxiety. Adverse reactions in patients aged 4 to <12 years were generally similar to patients aged 12 years and older.

DRUG INTERACTIONS
FYCOMPA may decrease the efficacy of contraceptives containing levonorgestrel. Plasma levels of perampanel were decreased when administered with known moderate and strong CYP3A4 inducers, including, carbamazepine, phenytoin, or oxcarbazepine. Multiple dosing of FYCOMPA 12 mg per day enhanced the effects of alcohol on vigilance and alertness, and increased levels of anger, confusion, and depression. These effects may also be seen when FYCOMPA is used in combination with other CNS depressants. These effects may also be seen when FYCOMPA is used in combination with other CNS depressants.

PREGNANCY AND LACTATION
Physicians are advised to recommend that pregnant patients taking FYCOMPA enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. Caution should be exercised when FYCOMPA is administered to pregnant or nursing women as there are no adequate data on the developmental risk associated with use in pregnant women, and no data on the presence of perampanel in human milk, the effects on the breastfed child, or the effects of the drug on milk production.

HEPATIC AND RENAL IMPAIRMENT
Use in patients with severe hepatic or severe renal impairment is not recommended. Dosage adjustments are recommended in patients with mild or moderate hepatic impairment. Use with caution in patients with moderate renal impairment.

DRUG ABUSE AND DEPENDENCE
FYCOMPA is a Schedule III controlled substance and has the potential to be abused and lead to drug dependence and withdrawal symptoms including anxiety, nervousness, irritability, fatigue, asthenia, mood swings, and insomnia.

Please see full Prescribing Information, including Boxed WARNING.

About FYCOMPA

FYCOMPA is a prescription medicine used in people with epilepsy aged 4 and older alone or with other medicines to treat partial-onset seizures with or without secondarily generalized seizures, and with other medicines to treat primary generalized tonic-clonic seizures for people with epilepsy aged 12 and older.

FYCOMPA, a unique oral medication, is a selective, non-competitive AMPA (alpha-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid) receptor antagonist. The precise mechanism by which FYCOMPA exerts its antiepileptic effects in humans is unknown. In a pharmacokinetic study, it has been demonstrated that because of its long half-life, a missed dose of FYCOMPA does not significantly impact plasma levels.

FYCOMPA is supplied as 2 mg, 4 mg, 6 mg, 8 mg, 10 mg and 12 mg film-coated tablets, and as a 0.5 mg/mL oral suspension formulation. FYCOMPA has been designated by the U.S. Drug Enforcement Administration as a federally-controlled substance (CIII). To date, FYCOMPA is approved in 72 countries and has been used to treat more than 300,000 patients worldwide across all indications.

About Epilepsy
Epilepsy is a medical condition that produces seizures affecting a variety of mental and physical functions. Epilepsy is one of the most common neurological disorders, which affects about 3.4 million people in the United States, including 470,000 children. Children with uncontrolled seizures are at greater risk for sudden unexpected death in epilepsy (SUDEP), which is relatively uncommon in childhood, but the risk increases if epilepsy persists into adulthood.

Partial-onset seizures are the most common type of seizure seen in people with epilepsy, accounting for 60 percent of all seizures. Convulsive seizures account for up to 25 percent of all epilepsy, with primary generalized tonic-clonic seizures being one of the most common and severe forms of seizures.

Missed medication doses are the number one cause of breakthrough seizures, which can cause significant injury to patients. People who experience breakthrough seizures have an increased risk of fractures or head injuries, emergency room (ER) visits, and hospitalization, as well as an associated increase in healthcare costs.

About Eisai
Eisai is a leading global research and development-based pharmaceutical company headquartered in Japan, with approximately 10,000 employees worldwide. We define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call our human health care (hhc) philosophy. We strive to realize our hhc philosophy by delivering innovative products in therapeutic areas with high unmet medical needs, including Oncology and Neurology. In the spirit of hhc, we take that commitment even further by applying our scientific expertise, clinical capabilities and patient insights to discover and develop innovative solutions that help address society's toughest unmet needs, including neglected tropical diseases and the Sustainable Development Goals.

For more information about Eisai, please visit www.eisai.com (for global), us.eisai.com (for U.S.) or www.eisai.co.uk (for U.K.), and connect with us on Twitter (U.S. and global) and LinkedIn (for U.S.).

Media Inquiries:

Christopher Vancheri Eisai Inc.
551-305-0050
christopher_vancheri@eisai.com

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