New Analyses Evaluate Long-Term Convulsive Seizure Freedom Rates With Use Of Adjunctive FYCOMPA® (perampanel) CIII In Adult Patients Presented at Annual Meeting of the AES

-- In a real-world, observational, retrospective study of FYCOMPA as a first add-on therapy, 61% (19/31) of patients with generalized seizures achieved seizure freedom, with an overall retention rate of 85% (127/149) at 12 months
-- 53% (42/78) of patients with secondarily generalized seizures were seizure free at 2 years and close to 35% (22/63) at 3 years in a post-hoc analysis of an open-label extension study
-- For patients on 3 or more antiepileptic drugs (AEDs), there was a greater reduction in all-cause and epilepsy-related hospitalizations in those treated with FYCOMPA vs lacosamide in a retrospective health economics analysis
-- Data was presented supporting the recent U.S. Food and Drug Administration (FDA) approval of FYCOMPA for pediatric patients with epilepsy 4 years of age and older with partial-onset seizures (POS)

WOODCLIFF LAKE, N.J./PRNewswire/ -- Eisai Inc. presented new data on FYCOMPA^®(perampanel) CIII at the American Epilepsy Society Annual Meeting in New Orleans which included analyses of convulsive seizure freedom rates in adult and pediatric epilepsy patients. More than 50 scientific posters on FYCOMPA were presented by both Eisai and independent investigators, underscoring a collective commitment to advancing research in epilepsy care.

Of note, Eisai presented three post-hoc analyses evaluating the potential of FYCOMPA to help patients experience long-term, sustained convulsive seizure freedom, as well as data that supported the recent U.S. Food and Drug Administration (FDA) approval of FYCOMPA for monotherapy and adjunctive use in pediatric patients 4 years and older for the treatment of partial-onset seizures (POS) with or without secondarily generalized seizures. Additional data included all-cause and epilepsy-related hospitalizations with use of FYCOMPA compared to lacosamide.

"These long-term seizure freedom data showed about 53% of patients with secondarily generalized seizures experienced convulsive seizure freedom at 2 years and close to 35% at 3 years," said Trevor Resnick, MD, Pediatric Neurologist at Nicklaus Children's Hospital. "These results are very encouraging for patients who are affected by uncontrolled convulsive seizures and for whom seizure freedom remains an important treatment goal."

FYCOMPA was initially approved for adjunctive use in POS in patients 12 years and older in 2012 and was later approved as adjunctive therapy for PGTC seizures in patients with epilepsy 12 years of age and older, and then as monotherapy for POS with or without secondarily generalized seizures in patients with epilepsy 12 years of age and older. In September 2018, FYCOMPA was approved for monotherapy and adjunctive use in pediatric patients 4 years and older for the treatment of POS with or without secondarily generalized seizures.

"The broad scope of FYCOMPA data being presented highlights how FYCOMPA may help both children and adults on their journey toward the goal of seizure freedom," said Ivan Cheung, Chairman and CEO, Eisai Inc. "These data encourage us to continue the important work of conducting research that leads to improved clinical outcomes for these patients."

To date, FYCOMPA is approved in 55 countries and has been used to treat more than 200,000 patients worldwide across all indications.

Key data presented include:
Some of these data include post hoc exploratory or retrospective analyses. These results should be interpreted cautiously. Additionally, the open-label studies did not include a control arm. Potential confounders, including changes in background AEDs and the potential association between treatment duration and different tolerability could have influenced study results.

Poster presentation number: 1.307
Saturday, December 1, 12:00 p.m. to 2:00 p.m. 
Effectiveness and tolerability of FYCOMPA (perampanel) in adolescents and adults as a first add-on therapy. An observational multicenter study
Summary: A multicenter, observational, retrospective study performed in 22 Spanish hospitals evaluated the efficacy and tolerability of FYCOMPA used as first add-on in non-refractory epilepsy in everyday clinical practice. The statistical analysis of this independent study was supported by an unrestricted grant by Eisai Farmacêutica S.A. In total, 149 patients were included in this analysis. Focal epilepsy was the most frequent epilepsy type (n=113; 77.9%) and temporal lobe epilepsy the most frequent subtype (n=39; 26.9%). The main reason for FYCOMPA treatment was poor seizure control (n=104; 86.0%). After 12 months, FYCOMPA mean dose was 6.2 mg/day (2-12 mg/day). The most frequent titration scheme was 2 mg every four weeks (39.7%), followed by 2 mg every two weeks. 85.5% of patients were treated with one previous monotherapy. Retention rate of FYCOMPA at 3 months was 98% (n=146), at 6 months 88.6% (n=132) and at 12 months 85.2% (n=127). After 12 months, 126 patients (84.6%) were responders (≥50% reduction in seizure frequency): 98/118 (83.1%) with focal seizures and 26/31 (83.9%) with generalized seizures. Seizure freedom was achieved in 68 patients (45.6%) by the end of the study: 46/118 (39%) with partial seizures and 19/31 (61.3%) with generalized seizures. A total of 72 patients (48.3%) experienced at least 1 adverse event (AE) during the follow-up, with the majority of AEs reported as mild/moderate. The most frequently reported AEs were dizziness (15.4%), irritability (14.1%) and somnolence (14.1%). FYCOMPA withdrawal due to an AE occurred in 16 patients (10.7%), with irritability being the most frequent AE.

Poster presentation number: 2.255
Sunday, December 2, 12:00 p.m. to 2:00 p.m. 
Sustained seizure-free status with adjunctive FYCOMPA (perampanel) for patients with secondarily generalized (SG) seizures during an open-label extension (OLEx): Study 307  
Summary:  Patients who completed one of 3 phase III double-blind, placebo-controlled studies entered the OLEx study 307.This post hoc analysis included patients ≥12 years with SG seizures who participated in Study 307 and achieved SG seizure-free status during either the preceding double-blind studies or the OLEx. Of the 80 patients who received adjunctive FYCOMPA (<12 mg/day) and achieved SG seizure-free status during the double-blind phase, 53% (42/78) remained SG seizure free for 24 months and 35% (22/63) remained SG seizure free for 36 months. Number of patients decreased over time due to patients dropping out of the study.

Poster presentation number: 2.256
Sunday, December 2, 12:00 p.m. to 2:00 p.m. 
Sustained seizure-free status with adjunctive FYCOMPA (perampanel) for patients with primary generalized tonic-clonic (PGTC) seizures during the open-label extension (OLEx) phase of Study 332 
Summary: This post hoc analysis investigated PGTC seizure-free status rates during adjunctive treatment with FYCOMPA ≤12 mg/day in patients aged ≥12 years from the double-blind and OLEx phase of Study 332. Seizure-free rates were assessed at 6, 12, 18 and 24 months in patients who achieved PGTC seizure-free status during the double-blind phase. Patients were also assessed for ≥6 and ≥12 months at any time during the FYCOMPA treatment duration (double-blind and OLEx phases). During the double-blind phase, 35 out of 162 patients (21%) were PGTC seizure free. Of the 35 patients, 25 were treated with FYCOMPA and 84%, 56%, 45.8%, and 31.6% of patients remained PGTC seizure free for 6, 12, 18, and 24 months, respectively. Over the entire FYCOMPA treatment duration, 73 patients were PGTC seizure free for ≥6 months, and 41 patients were PGTC seizure free for ≥12 months.

Poster presentation number: 2.152
Sunday, December 2, 12:00 p.m. to 2:00 p.m.
Inpatient hospitalizations rates in patients diagnosed with epilepsy and treated with FYCOMPA (perampanel) or lacosamide 
Summary: The retrospective analysis of claims data included 1,717 patients in each cohort (at least 12 years or older) who were treated with FYCOMPA or lacosamide, another antiepileptic drug (AED), and if they had at least two diagnoses of epilepsy or non-febrile convulsions. All-cause and epilepsy-related hospitalization rates were observed for one year following the start of treatment. There was a greater reduction (9.6%) in all-cause hospitalizations for patients on FYCOMPA compared to those patients on lacosamide (5.8%). Epilepsy-related hospitalizations also decreased (9.9% vs. 8.3% for FYCOMPA and lacosamide, respectively). Among those who had any hospitalization in the baseline period, patients treated with FYCOMPA had a 59.9% reduction in all-cause hospitalizations vs. a 48.6% reduction for those treated with lacosamide.  A similar result was seen for epilepsy-related hospitalizations, a reduction of 65% vs. 58%, respectively. Because of the limitations of claims data, it was not known if patients were taking the approved dosage of FYCOMPA or if all patients had partial-onset seizures or primary generalized tonic-clonic seizures to be consistent with FYCOMPA's approved use.

Poster presentation number: 2.257
Sunday, December 2, 12:00 p.m. to 2:00 p.m. 
Efficacy and safety of adjunctive FYCOMPA (perampanel) 4 mg/day for the treatment of partial-onset seizures (POS): pooled analysis of four randomized Phase III studies 
Summary: Here, we report a post hoc, pooled analysis from four randomized Phase III studies (Studies 304, 305, 306 and 335), based on actual FYCOMPA dose received, which may have differed from the randomized dose, to evaluate the efficacy and safety of adjunctive FYCOMPA 4 mg/day in patients aged ≥12 years with POS with/without SG seizures. In the analysis 363 patients received the actual FYCOMPA 4 mg/day dose and 616 patients received placebo. Efficacy assessments included median percent reductions in seizure frequency per 28 days from baseline during the double-blind phase and seizure-free status rates during maintenance for POS (all patients) or SG seizures (patients who had SG seizures during baseline). FYCOMPA had greater median percent reductions in seizure frequency per 28 days for POS and SG seizures compared with placebo (21.1% vs 12.6% and 49.8% vs 17.4%, respectively). Seizure-free status rates during maintenance also increased with FYCOMPA vs placebo for both POS and SG seizures (3.6% vs 0.8% and 18.7% vs 11.1%, respectively). The most common treatment-emergent adverse events (TEAEs) in both seizure groups was dizziness.

Poster presentation number: 3.289
Monday, December 3, 12:00 p.m. to 2:00 p.m. 
Study 311: Safety and efficacy of adjunctive FYCOMPA (perampanel) in pediatric patients (aged 4 to <12 years) with partial-onset seizures (POS) or primary generalized tonic-clonic (PGTC) seizures
Summary: Study 311 is an open-label, single-arm study of FYCOMPA in pediatric patients with inadequately controlled POS or PGTC. The core study consists of a 4-week pre-treatment period (screening/baseline), 23-week treatment period (11 weeks titration; 12 weeks maintenance), and a 4-week follow-up period. At interim data cutoff, 161 patients (POS, n=135; PGTC, n=26) received at least one dose of FYCOMPA, with 77 completing the core study (of whom 73 entered the extension study; 28 discontinued). There was an improvement (median % reduction per 28 days) from baseline in seizure frequency per 28 days in patients with POS (36%, n=135) or PGTC (81.9%, n=15). Nearly 20% (n=46) of patients with SG seizures and 53% (n=15) with PGTC were seizure free at 3 months. The most common TEAEs were somnolence, nasopharyngitis, dizziness and irritability. 

Poster presentation number: 3.287
Monday, December 3, 12:00 p.m. to 2:00 p.m. 
Study 311: Safety and efficacy of adjunctive FYCOMPA (perampanel) in pediatric patients (aged 4 to <7 years, 7 to <12 years) with partial-onset seizures (POS) or primary generalized tonic-clonic (PGTC) seizures 
Summary: Study 311 is an open-label, single-arm study of FYCOMPA in pediatric patients with inadequately controlled POS or PGTC. The core study consists of a 4-week pre-treatment period (screening/baseline), 23-week treatment period (11 weeks titration; 12 weeks maintenance), and a 4-week follow-up period. At interim data cutoff, 161 patients received at least one dose of FYCOMPA, with 77 completing the core study (of whom 73 entered the extension study; 28 discontinued). In this sub-group analysis, patients were stratified by age (4 to < 7 years, n=41; 7 to < 12 years, n=120). In younger (4 to <7 years) and older (7 to <12 years) pediatric patients, 50% responder rates were similar between younger and older pediatric patients experiencing POS (4 to <7 years, 50%; 7 to <12 years, 41.4%), and were greater for younger vs older pediatric patients experiencing PGTC (100% vs 53.8%) or SG (71.4% vs 50%), although the number of patients in these younger patient seizure populations were low (n=2 and n=14 for PGTC and SG, respectively). The most common TEAEs were somnolence, nasopharyngitis, dizziness and irritability. 

The safety and effectiveness of FYCOMPA for the treatment of partial-onset seizures in pediatric patients less than 4 years of age or for the treatment of primary generalized tonic-clonic seizures in pediatric patients less than 12 years of age have not been established.

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 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).

Please visit www.FYCOMPA.com to learn more about the treatment.

INDICATION 
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

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.

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.

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 Prescribing Information for FYCOMPA.

Contact:

Media Inquiries 
Michele Randazzo
Eisai Inc.
201-746-2979