WOODCLIFF LAKE, N.J., Dec. 7, 2021 /PRNewswire/ -- Eisai Inc. presented data from PERMIT, a large real-world clinical study evaluating its antiepileptic drug (AED) FYCOMPA® (perampanel) CIII, including as monotherapy and early add-on therapy for focal and generalized seizures at the 2021 American Epilepsy Society (AES) Annual Meeting. In this global pooled analysis, among the adult epilepsy patients with effectiveness assessed by seizure type, patients with focal seizures only, had seizure freedom and responder rates of 14.5% and 44.6% at the last visit, respectively. Among patients with generalized seizures only, seizure freedom and responder rates at the last visit were 52.0% and 73.3%, respectively.

Overall, 50.7% (1,935/3,817) of patients experienced adverse events (AEs). The most common AEs were dizziness/vertigo (16.0%), somnolence (10.7%), irritability (8.3%) and behavioral disorders (5.1%). Psychiatric AEs were reported for 21.0% (n=797/3,794) of patients and led to discontinuation in 9.4% (n=337/3,586) of patients over the course of 12 months. Over 12 months, 16.8% (n=597/3,554) patients discontinued due to AEs.

"The 42 presentations at this year's American Epilepsy Society Meeting convey the depth of our commitment to the patients and families impacted by this challenging disease," said Ivan Cheung, Chairman, Eisai Inc. and Global President, Neurology Business Group, Eisai Co., Ltd. "We are excited to be sharing new data that evaluate the efficacy and tolerability of FYCOMPA in treating epilepsy patients in clinical practice settings, as well as the latest update from the FREEDOM study that shows the efficacy of long-term use of FYCOMPA monotherapy."

PERMIT was a retrospective pooled analysis of individual patient data from 44 real-world studies/work groups from 17 countries, in which patients with focal and generalized epilepsy were treated with FYCOMPA. The study evaluated more than 5,000 patients with focal and generalized epilepsy, was presented across 13 posters, and included data on FYCOMPA monotherapy, early add-on therapy, and results from specific patient groups.

• At the last visit, seizure freedom rates with FYCOMPA monotherapy in patients with focal-onset seizures and generalized-onset seizures were 64.1% (n=84/131) and 69.4% (n=34/49), respectively, and corresponding responder rates were 84.4% (n=108/128) and 93.9% (n=46/49), respectively. Overall, 45.2% (n=89/197) of patients experienced AEs and 13.7% (n=18/131) of patients discontinued due to AEs over 12 months. The most frequently reported AEs (≥5% of patients) were dizziness/vertigo (16.8%), irritability (11.2%), somnolence (9.1%) and depression (6.6%).
• In patients treated with FYCOMPA as an early add-on therapy, retention rates were significantly higher versus late add-on therapy at all timepoints (month 12: 77.1% (n=448/581) vs. 61.8% (n=1,023/1,656); p<0.001). At the last visit, the seizure freedom rate was significantly higher in patients treated with early versus late add-on therapy (40.1% (n=236/589) vs. 8.7%; (n=137/1,568) (p<0.001), as was responder rate (73.0% (n=427/585) vs. 36.4% (n=507/1,393); p<0.001). The incidence of AEs was significantly lower for patients treated with early versus late add-on therapy (41.8% (n=254/608) vs. 54.5% (n=932/1,711); p<0.001). The most frequently reported AEs (≥10% of patients) were dizziness/vertigo (early add-on, 8.7%; late add-on, 17.6%), somnolence (early add-on, 9.9%; late add-on, 11.6%) and irritability (early add-on, 10.1%; late add-on, 7.6%). Over 12 months, 15.0% (n=87/581) of early add-on patients and 18.7% (n=309/1,656) of late add-on patients discontinued due to AEs (p=0.045). Psychiatric AEs were reported for 18.3% (n=111/606) and 22.2% (n=376/1,695) of early and late add-on patients, respectively (p=0.046).
• In elderly epilepsy patients with focal and generalized seizures treated with FYCOMPA, at the last visit, seizure freedom rates were 38.2% (n=91/238) and 53.3% (n=8/15), respectively. Overall, 54.8% (n=164/299) of patients experienced AEs and 23.7% (n=69/291) of patients discontinued due to adverse events over 12 months. The most frequently reported AEs (≥5% of patients) were dizziness/vertigo (16.4%), somnolence (12.0%), irritability (8.4%) and instability/ataxia (7.4%).
• In epilepsy patients with tumor etiology treated with FYCOMPA, at the last visit, responder and seizure freedom rates were 66.9% (n=79/118) and 34.2% (n=41/120), respectively. Overall, 36.2% (n=42/116) of patients experienced AEs and 16.8% (n=16/95) of patients discontinued due to adverse events over 12 months. The most frequently reported AEs (≥5% of patients) were dizziness/vertigo (13.8%) somnolence (9.5%) and irritability (7.8%).
• In patients with myoclonic seizures treated with FYCOMPA, at the last visit, responder and seizure freedom rates were 85.9% (n=110/128) and 63.4% (n=90/142), respectively. Overall, 46.8% (n=73/156) of patients experienced AEs and 14.0% (n=16/114) of patients discontinued due to AEs over 12 months. The most frequently reported AEs (>5% of patients) were dizziness/vertigo (19.2%), somnolence (18.6%) and fatigue (9.6%).

"Real-world data is important to convey information about a more comprehensive group of epilepsy patients than is typically recruited in clinical 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 further support potential of FYCOMPA as a monotherapy and as a first add-on for patients with focal and generalized seizures, as well as in the treatment of a variety of epilepsy patients including elderly patients and those with tumor etiology."

FREEDOM Study Update
The FREEDOM study was a single-arm, open-label, Phase III study that evaluated the efficacy and tolerability of FYCOMPA monotherapy at a maintenance dose of 4 to 8 mg/day in patients aged ≥ 12 years with newly diagnosed or currently untreated recurrent FOS, with or without FBTCS, in Japan and South Korea. This study consisted of a Core Study [4-week pretreatment and 32-week treatment (6-week titration; 26-week maintenance) phases], and an optional Extension Phase (additional 26 weeks of treatment).

Final efficacy and safety results from the FREEDOM study Extension Phase at 52 weeks were also presented. Overall in the mITT analysis set, secondary endpoints also included 75.0% (n=24/32) of patients who entered the extension phase (an additional 26 weeks of treatment) from the 4-mg/day treatment phase of 26 weeks, and 79.5% (n=31/39) of patients who entered from the 4- and/or 8- mg/day treatment phase (26 weeks) while seizure free had sustained seizure freedom for 52 weeks. Secondary endpoints also included TEAEs (treatment emergent adverse events) which occurred in 83.1% (n=74/89) of patients in the Safety Analysis Set across the Core Study plus Extension Phase. The most common TEAEs were dizziness (38.2%), nasopharyngitis (21.3%), headache (14.6%), and somnolence (13.5%).

An update on the latest analysis of the FREEDOM study (342 extension phase) assessing the impact of long-term (up to 52 weeks) FYCOMPA monotherapy on health-related quality of life in patients with newly diagnosed/currently untreated recurrent focal seizures was also presented. In each domain of the EQ-5D-5L (mobility, self-care, performing usual activities, pain/discomfort, and anxiety/depression), included as an exploratory endpoint in the mITT analysis set, ≥77.5% of patients reported no problems at baseline and ≥77.5% of patients reported no problems at the end of treatment.

Key data presented:
Limitations of PERMIT include its retrospective pooled analysis that were heterogeneous in terms of their objectives and information reported. Due to this, data were not available for all people with epilepsy at all timepoints, across all endpoints and assessments. In addition, seizure freedom was defined as no seizures since at least the prior visit.

Limitations of FREEDOM include its open-label study design with no placebo control arm due to ethical concerns, no adjustment from multiplicity was included, and the data are descriptive.

Poster presentation number: # V.052
Poster session: Thursday, December 9, 2021 4:00 p.m. to 5:00 p.m. CST

Pooled Analysis of Adult Epilepsy Patients Treated with Perampanel in Everyday Clinical Practice (PERMIT Study)

Summary:
A pooled analysis was conducted of 44 prospective, retrospective and cross-sectional clinical practice studies/work groups that have collected data on adult patients treated with FYCOMPA for focal and/or generalized seizures. Effectiveness was assessed by seizure type (focal, generalized), at the last visit (last observation carried forward). Retention was assessed after 3, 6, and 12 months of FYCOMPA treatment. Effectiveness was assessed by evaluating seizure freedom rate (no reported seizures since at least the prior visit), responder rate (≥50% reduction in seizure frequency from baseline) and the proportion of patients with unchanged or worsening seizure frequency. Safety and tolerability was assessed by evaluating adverse events (AEs), psychiatric AEs, and AEs leading to discontinuation.

Effectiveness was assessed for 3,644 patients; safety/tolerability was assessed for 3,817 patients. Retention rates at 3, 6, and 12 months were 90.9% (n=3,593/3,954), 80.1% (n=3,023/3,775) and 64.8% (n=2,302/3,554), respectively. Mean retention time on FYCOMPA treatment was 10.8 months. Among patients with focal seizures only, seizure freedom and responder rates at the last visit were 14.5% (n=419/2883) and 44.6% (n=1152/2582), respectively. The proportions of patients with unchanged or worsening seizure frequency at the last visit were 26.3% (667/2535) and 11.8% (298/2535), respectively. The proportions of patients with unchanged or worsening seizure frequency at the last visit were 13.5% (55/407) and 5.9% (24/407), respectively. Among patients with generalized seizures only, seizure freedom and responder rates at the last visit were 52.0% (n=224/431)and 73.3% (n=299/408), respectively.

Overall, 50.7% (n=1,935/3,817) of patients experienced adverse events (AEs). The most common AEs were dizziness/vertigo (16.0%), somnolence (10.7%), irritability (8.3%) and behavioral disorders (5.1%). Over 12 months, 16.8% (n=597/3,554) discontinued due to AEs. Psychiatric AEs were reported for 21.0% (n=797/3,794) of patients and led to discontinuation in 9.4% (n=337/3,586) of patients. The psychiatric AEs that most frequently led to discontinuation (≥1% of patients) were irritability (3.2%), behavioral disorders (2.6%) and mood disturbance (2.3%).

Poster presentation number: # V.043
Poster session: Thursday, December 9, 2021 10:00 a.m. to 11:00 a.m. CST

Real-World Experience of Perampanel Monotherapy in Epilepsy Patients with Focal-Onset and Generalized-Onset Seizures (PERMIT Study)

Summary:
Patients treated with FYCOMPA monotherapy (first-line or conversion to monotherapy) for focal and/or generalized seizures were identified from a pooled analysis of 44 prospective, retrospective and cross- sectional clinical practice studies/work groups. 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 (last observation carried forward). Effectiveness assessments comprised seizure freedom rate (no seizures since at least the prior visit), responder rate (≥50% seizure frequency reduction from baseline), and the proportions of patients with unchanged or worsening seizure frequency. Safety and tolerability were assessed by evaluating adverse events (AEs), psychiatric AEs, and AEs leading to discontinuation.

At 3, 6 and 12 months, retention rates were 91.1% (n=153/168), 87.3% (n=138/158) and 73.3% (n=96/131), respectively. Mean (95% confidence interval) time under FYCOMPA treatment was 11.8 (11.2 to 12.5) months. At last visit, seizure freedom rates in patients with focal and generalized seizures were 64.1% (n=84/131) and 69.4% (n=34/49), respectively, and corresponding responder rates were 84.4% (n=108/128) and 93.9% (n=46/49), respectively. AEs were reported for 45.2% (n=89/197) of patients; the most frequently reported AEs (≥5% of patients) were dizziness/vertigo (16.8%), irritability (11.2%), somnolence (9.1%) and depression (6.6%). Over 12 months, 13.7% (n=18/131) of patients discontinued due to AEs. Psychiatric AEs were reported for 20.8% (n=41/197) of patients and led to discontinuation of 10.2% (n=17/166) of patients.

Poster presentation number: # 3.213
Poster session: Monday, December 6, 2021 12:00 p.m. to 1:45 p.m. CST

Perampanel as Early Add-on Therapy for Epilepsy Patients with Focal-Onset and Generalized- Onset Seizures Treated in Clinical Practice (PERMIT Study)

Summary:
Patients treated with FYCOMPA for focal and/or generalized seizures were identified from a pooled analysis of 44 prospective, retrospective and cross-sectional clinical practice studies/work groups. Data were compared for patients treated with FYCOMPA as early add-on therapy versus late add-on therapy (as defined by each individual study). Effectiveness was assessed at the last visit (last observation carried forward). Retention was assessed after 3, 6, and 12 months of FYCOMPA treatment. Effectiveness assessments included responder rate (≥50% seizure frequency reduction from baseline), seizure freedom rate (no seizures since at least the prior visit), and the proportions of patients with unchanged or worsening seizure frequency. Safety and tolerability were assessed by evaluating AEs, psychiatric AEs, and AEs leading to discontinuation.

Retention was assessed for 2,437 patients (early add-on, n=622/2,437; late add-on, n=1,815/2,437); effectiveness for 2,190 patients (early add-on, n=592; late add-on, n=1,598); and safety/tolerability for 2,319 patients (early add-on, n=608/2,319; late add-on, n=1,711/2,319). Retention rates were significantly higher for patients treated with early versus late add-on therapy at all timepoints (month 12: 77.1% (n=448/581) vs. 61.8% (n=1023/1656); p<0.001). At the last visit (last observation carried forward), seizure freedom rate was significantly higher in patients treated with early versus late add-on therapy (40.1% (n=236/589) vs. 8.7% (n=137/1568); p<0.001), as was responder rate (73.0% (n=427/585) vs. 36.4% (n=507/1393); p<0.001). At the last visit, the proportion of patients with unchanged seizure frequency was significantly lower in patients treated with early versus late add-on therapy (10.2% (n=59/577) vs. 31.8% (n=435/1369); p<0.001), as was the proportion of patients with worsening seizure frequency (6.1% (n=35/577) vs. 13.6% (n=186/1369); p< 0.001).

The incidence of AEs was significantly lower for patients treated with early versus late add-on therapy (41.8% vs. 54.5%; p<0.001), as was the proportion of patients with psychiatric AEs (18.3% (n=111/606) vs. 22.2% (n=376/1695); p=0.046), and the rate of discontinuation due to AEs over 12 months (15.0% (n=87/581) vs. 18.7% (n=309/1656); p=0.045). The most frequently reported AEs (≥10% of patients) were dizziness/vertigo (early add-on, 8.7%; late add-on, 17.6%), somnolence (early add-on, 9.9%; late add-on, 11.6%) and irritability (early add-on, 10.1%; late add-on, 7.6%). Patients with psychiatric AEs who discontinued included 7.8% for early add-on (n=47/601) and 9.9% for late add-on (n=163/1,647).

Poster presentation number: # 1.215
Poster session: Saturday, December 4, 2021 12:00 p.m. to 2:00 p.m. CST

The Use of Perampanel in Elderly Epilepsy Patients: Pooled Analysis of Real-World Studies (PERMIT Study)

Summary:
Patients aged ≥65 years were identified from a pooled analysis of 44 prospective, retrospective and cross- sectional clinical practice studies/work groups. Retention was assessed after 3, 6, and 12 months of FYCOMPA treatment. Effectiveness was assessed at the last visit (last observation carried forward). Effectiveness was assessed by seizure type (focal or generalized) and included responder rate (≥50% seizure frequency reduction from baseline), seizure freedom rate (no seizures since at least the prior visit) and the proportions of patients with unchanged or worsening seizure frequency. Safety and tolerability were assessed by evaluating AEs, psychiatric AEs, and AEs leading to discontinuation. Retention was assessed for 316 patients; effectiveness for 283 patients; and safety/tolerability for 299 patients.

At the last visit, seizure freedom rates in patients with focal and generalized seizures were 38.2% (n=91/238) and 53.3% (n=8/15), respectively; the corresponding values for responder rates were 69.3% (n=156/225) and 76.9% (n=10/13), respectively. Retention rates at 3, 6 and 12 months were 86.7% (n=274/316), 76.5% (n=238/311) and 61.5% (n=179/291), respectively. The most common reasons for discontinuation were AEs (22.0%), lack of efficacy (6.2%) and both AEs and lack of efficacy (1.7%). AEs were reported for 54.8% (n=164/299) of patients and the most frequently reported AEs (≥5% of patients) were dizziness/vertigo (16.4%), somnolence (12.0%) irritability (8.4%) and instability/ataxia (7.4%). Over 12 months, 23.7% (n=69/291) discontinued due to AEs. Psychiatric AEs were reported for 18.5% (n=55/297) of patients and led to discontinuation in 9.9% (n=28/284) of patients. The psychiatric AEs that most frequently led to discontinuation (≥1% of patients) were irritability (4.2%), behavioral disorders (1.8%) and depression (1.4%).

Poster presentation number: # 3.211
Poster session: Thursday, December 9, 2021 10:00 a.m. to 11:00 a.m. CST

Clinical Practice Evidence for Perampanel in Epilepsy Patients with Tumor Etiology (PERMIT Study) 

Summary:
Patients with epilepsy with tumor etiology were identified from a pooled analysis of 44 prospective, retrospective and cross-sectional clinical practice studies/work groups. Retention was assessed after 3, 6, and 12 months of FYCOMPA treatment. Effectiveness was assessed at the last visit (last observation carried forward). Effectiveness assessments comprised responder rate (≥50% seizure frequency reduction from baseline), seizure freedom rate (no seizures since at least the prior visit), and the proportions of patients with unchanged or worsening seizure frequency. Safety and tolerability were assessed by evaluating AEs, psychiatric AEs, and AEs leading to discontinuation. Retention was assessed for 125 patients; effectiveness for 120 patients; safety and tolerability for 116 patients.

At the last visit (last observation carried forward), responder and seizure freedom rates were 66.9% (n=79/118) and 34.2% (n=41/120), respectively, and the percentages of patients with unchanged or worsening seizure frequency were 15.3% (n=18/118) and 6.8% (n=8/118), respectively. At 3, 6 and 12 months, retention rates were 88.0% (n=110/125), 79.5% (n=97/122) and 65.3% (n=62/95), respectively. Reasons for discontinuation included AEs (16.8%) and lack of efficacy (5.3%). AEs were reported for 36.2% (n=42/116) of patients; the most frequently reported AEs were dizziness/vertigo (13.8%), somnolence (9.5%), and irritability (7.8%). AEs led to discontinuation of 16.8% (n=16/95) of patients over 12 months and 13.0% (n=15/115) of patients experienced psychiatric AEs. Psychiatric AEs led to discontinuation of 8.8% (n=10/113) of patients.

Poster presentation number: # V.053
Poster session: Thursday, December 9, 2021 10:00 a.m. to 11:00 a.m. CST

Perampanel for the Treatment of Patients with Myoclonic Seizures in Clinical Practice (PERMIT Study)

Summary:
Patients with myoclonic seizures who were treated with FYCOMPA were identified from a pooled analysis of 44 prospective, retrospective and cross-sectional clinical practice studies/work groups. Retention was assessed after 3, 6, and 12 months of FYCOMPA treatment. Effectiveness was assessed after 3, 6, and 12 months and at the last visit (last observation carried forward). Effectiveness assessments comprised responder rate (≥50% seizure frequency reduction from baseline), seizure freedom rate (no seizures since at least the prior visit), and the proportions of patients with unchanged or worsening seizure frequency. Safety and tolerability were assessed by evaluating adverse events (AEs), psychiatric AEs, and AEs leading to discontinuation. Retention was assessed for 133 patients; effectiveness for 142 patients; and safety/ tolerability for 156 patients. Mean (standard deviation) FYCOMPA dose was 2.6 (1.1) mg/day at baseline and 5.5 (2.1) mg/day at the last visit (last observation carried forward).

Retention rates at 3, 6 and 12 months were 94.7% (n=126/133), 89.0% (n=113/127) and 80.7% (n=92/114), respectively. Reasons for discontinuation included AEs (11.4%), lack of efficacy (4.4%), and both AEs and lack of efficacy (2.6%). At the last visit, responder and seizure freedom rates were 85.9% (n=110/128) and 63.4% (n=90/142), respectively; and the proportions of patients with unchanged and worsening seizure frequency were 10.2% (n=13/128) and 3.1% (n=4/128), respectively. AEs were reported for 46.8% (n=73/156) of patients and psychiatric AEs were reported for 24.7% (n=38/154) of patients. The most frequently reported AEs (>5% of patients) were dizziness/vertigo (19.2%), somnolence (18.6%) and fatigue (9.6%). Over 12 months, 14.0% (n=16/114) of patients had discontinued due to AEs. Psychiatric AEs led to discontinuation of 6.0% (n=9/151) of patients.

Poster presentation number: # 2.201
Poster session: Sunday, December 5, 2021 12:00 p.m. to 2:00 p.m. CST

Long-Term Perampanel Monotherapy and Health-Related Quality of Life in Patients with Newly Diagnosed/Currently Untreated Recurrent Focal Seizures (FOS): FREEDOM Study 342 Extension Phase

Summary:
The FREEDOM study was a single-arm, open-label, Phase III study that evaluated FYCOMPA monotherapy at a maintenance dose of 4 to 8 mg/day in patients aged >/=12 years with newly diagnosed or currently untreated recurrent FOS, with or without FBTCS, in Japan and South Korea. This study consisted of a Core Study [4-week pretreatment and 32-week treatment (6-week titration; 26-week maintenance) phases], and an optional Extension Phase (additional 26 weeks of treatment).

During the core study, patients received FYCOMPA 4 mg/day (4-week pretreatment [baseline]; 32-week treatment [6-week titration; 26-week maintenance]). If a patient had a seizure, they could be up-titrated to 8 mg/day (4-week titration; 26-week maintenance). Patients who could not tolerate FYCOMPA 8 mg/day were allowed to down-titrate to 6 mg/day based on the investigators' discretion. Patients could enter an extension phase for an additional 26 weeks (total: 52 weeks of treatment). EQ-5D-5L (exploratory endpoint) was assessed (mITT) and included 5 domains (mobility, self-care, doing usual activities, pain/discomfort, and anxiety/ depression); EQ visual analog scale (VAS) was also assessed.

Based on 71 patients with non-missing data (mITT Analysis Set), the mean (standard deviation) change in EQ VAS from baseline to end of treatment (up to 52 weeks) was 0.9 (15.4). In each domain of the EQ-5D-5L, ≥ 77.5% of patients reported no problems at baseline and ≥ 77.5% of patients reported no problems at end of treatment. No patients reported an inability to carry out the activity/extreme problems at baseline/end of treatment. Based on the shift from baseline analyses, most (≥ 60.6%) patients remained at the same level at the end of treatment as at baseline, 2.8–21.1% showed an improvement of problems across domains, and 7.0–18.3% patients had a worsening of problems across domains (mobility, self-care, performing usual activities, pain/discomfort, and anxiety/depression).

Poster presentation number: # 1.283
Poster session: Thursday, December 9, 2021 10:00 a.m. to 11:00 a.m. EST

Long-Term Efficacy and Safety of Perampanel Monotherapy in Patients with Newly Diagnosed/Currently Untreated Recurrent Focal-Onset Seizures: FREEDOM Study 342 Extension Phase

Summary:
The FREEDOM study was a single-arm, open-label, Phase III study that evaluated FYCOMPA monotherapy at a maintenance dose of 4 to 8 mg/day in patients aged >/=12 years with newly diagnosed or currently untreated recurrent FOS, with or without FBTCS, in Japan and South Korea. This study consisted of a Core Study [4-week pretreatment and 32-week treatment (6-week titration; 26-week maintenance) phases], and an optional Extension Phase (additional 26 weeks of treatment).

During the core study, patients received FYCOMPA 4 mg/day (4-week pretreatment; 32-week treatment [6-week titration; 26-week maintenance]). If a patient had a seizure, they could be up-titrated to 8 mg/day (4-week titration; 26-week maintenance). Patients who could not tolerate perampanel 8 mg/day were allowed to down-titrate to 6 mg/day based on the investigators' discretion. Patients could enter the extension for an additional 26 weeks (total: 52 weeks). 52-week seizure-freedom rates (modified Intent-to-Treat [mITT] Analysis Set), time to first seizure onset/withdrawal from the study from the first date of the maintenance period (modified Intent-to-Treat [mITT] Analysis Set), and TEAEs (core/extension) were assessed (Safety Analysis Set) as secondary endpoints.

Overall, 68.7% (n=46/67) of eligible patients entered the extension (39 who completed the 4- [n=32] or 8-mg/day [n=7] treatment phases and 7 who discontinued the 8-mg/day treatment phase); 38 patients completed the extension and 8 discontinued, most commonly due to withdrawal of consent (n=3 [6.5%]). Overall, 75.0% (n=24/32) of patients who entered the extension from the 4-mg/day treatment phase and 79.5% (n=31/39) of patients who entered from the 4- and/or 8- mg/day treatment phase while seizure free had sustained seizure freedom for 52 weeks (core study plus extension). TEAEs occurred in 83.1% (n=74/89) of patients (core/extension). The most common TEAEs were dizziness (38.2%), nasopharyngitis (21.3%), headache (14.6%), and somnolence (13.5%).

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

WARNING: SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS

• Serious or life-threatening psychiatric and behavioral adverse reactions including aggression, hostility, irritability, anger, and homicidal ideation and threats have been reported in patients taking FYCOMPA
• These reactions occurred in patients with and without prior psychiatric history, prior aggressive behavior, or concomitant use of medications associated with hostility and aggression
• Advise patients and caregivers to contact a healthcare provider immediately if any of these reactions or changes in mood, behavior, or personality that are not typical for the patient are observed while taking FYCOMPA or after discontinuing FYCOMPA
• Closely monitor patients particularly during the titration period and at higher doses
• FYCOMPA should be reduced if these symptoms occur and should be discontinued immediately if symptoms are severe or are worsening

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 has been approved in more than 70 countries and territories and has been used to treat more than 410,000 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

SOURCE Eisai Inc.