WOODCLIFF LAKE, N.J., May 9, 2019 /PRNewswire/ -- Eisai Inc. presented the latest clinical results on FYCOMPA^® (perampanel) CIII, at the 2019 American Academy of Neurology Annual Meeting in Philadelphia, including analyses highlighting the health and economic benefits of FYCOMPA. Twenty-one scientific abstracts were presented by both Eisai and independent investigators, underscoring a collective commitment to advancing research in epilepsy care across the age spectrum.

"At Eisai, we are working to develop solutions, including medications and technology, with the ultimate goal of helping epilepsy patients achieve seizure freedom," said Lynn Kramer, MD, Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai Inc. "The FYCOMPA data we've presented at AAN provides insights that we hope will help improve patient care and shows Eisai's commitment to continuing research that supports the epilepsy community in this mission."

Key findings show that:

• Patients treated with perampanel had a significantly greater reduction in all-cause hospitalizations compared to those treated with lacosamide, (25.3% vs 30.3%; p=0.0010; respectively). A similar result was seen for epilepsy-related hospitalizations (a reduction of 19.6% vs. 22.6%; p=0.0376, perampanel and lacosamide, respectively).
• The risk of all-cause inpatient hospitalizations decreased in Medicaid patients with epilepsy who were treated with perampanel for one year (38% pre-perampanel vs 30% post-perampanel; risk ratio of 0.79 [0.69-0.90]). A similar result was seen for epilepsy-related hospitalizations (32% pre-perampanel vs 25% post-perampanel; risk ratio of 0.78 [0.67-0.91]).
• In patients with uncontrolled epilepsy, treatment with a long half-life AED was associated with a significantly lower risk of hospitalization than those treated with a short half-life AED (in both unadjusted [0.81, 95% CI: 0.73, 0.89; p<0.001] and adjusted relative risk of hospitalization [0.84, 95% CI: 0.76, 0.93; p=0.0007]).

"Uncontrolled epilepsy has been associated with higher hospitalization rates, longer hospital stays and more frequent emergency room visits, resulting in greater morbidity and higher health care costs for patients," said Manoj Malhotra, MD, Vice President, Head of Medical Affairs at Eisai. "This hospitalization data suggests that starting FYCOMPA can be a benefit for patients who are looking for a treatment regimen that requires less frequent dosing."

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. FYCOMPA was first approved in 2012 for adjunctive use in partial-onset seizures (POS) in patients 12 years and older. In 2015, it was approved as adjunctive therapy for PGTC seizures in patients with epilepsy 12 years and older.

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. Please see limitations below.

Poster presentation number: 5-022
Tuesday, May 7, 2019, 5:30-6:30 p.m.
Inpatient Hospitalization Risk in Patients with Epilepsy Before and After Perampanel Treatment
Edward Faught, MD, Xuan Li, MS, Jiyoon Choi, PharmD, Manoj Malhotra, MD, Russell L. Knoth, PhD

Summary: In a retrospective study, a nationally representative medical and pharmacy claims database was used to identify 1,771 patients who had filled a perampanel prescription between July 2014 and June 2016. Patients were selected if they were 4-11 years old with any partial-onset (focal) seizures (POS), or ≥12 years with any POS or any primary generalized tonic–clonic seizures (GTCS), had continuous observations for the one-year period prior to and following this date. Clinical outcome variables were the one-year all-cause and epilepsy-related relative risk of inpatient hospitalization following perampanel initiation. Compared to the pre-index period, the post-perampanel period was associated with a significantly lower risk of inpatient hospitalization. The one-year all-cause inpatient hospitalization risk ratio was 0.76 (0.71-0.82), with a 36.2% hospitalization risk during the pre-period compared to 29.5% risk in the one-year follow-up period. Similarly, the one-year epilepsy-related inpatient hospitalization risk ratio was 0.72 (0.66-0.79), with 30.8% during the pre-index period, compared to 23.9% during the follow-up period. The Symphony Health database is an administrative claims database and may contain errors or omissions in codes for procedures, diagnoses, or dispensing. Impact of perampanel use on emergency room visits could not be examined, as these were not identified separately in the database and may be included under outpatient or inpatient visits.

Poster presentation number: 5-014
Thursday, May 9, 2019, 5:30-6:30 p.m.
Inpatient Hospitalization Risk in Medicaid Patients with Epilepsy Before and After Perampanel Treatment
Debanjana Chatterjee, PhD, Xuan Li, MS, Manoj Malhotra, MD, Jiyoon Choi, PharmD

Summary: For this analysis, a nationally representative medical and pharmacy claims database was used to identify 614 Medicaid patients who filled a perampanel prescription between July 2014 to June 2016. Patients were selected if they were 4-11 years old with any partial-onset (focal) seizures (POS), or ≥12 years with any POS or any primary generalized tonic–clonic seizures (GTCS), had continuous observations for the one-year period prior to and following this date. Outcome variables were the one-year all-cause and epilepsy-related relative risk of inpatient hospitalization following perampanel initiation. Compared to the pre-index period, the post-perampanel period was associated with a significantly lower risk of inpatient hospitalization. The one-year all-cause inpatient hospitalization risk ratio was 0.79 (0.69-0.90), with 38.3% during the pre-period compared to 30.3% in the one-year follow-up period. Similarly, the one-year epilepsy-related inpatient hospitalization risk ratio was 0.78 (0.67-0.91), with 32.2% hospitalization risk during the pre-index period, compared to 25.2% risk during the follow-up period. The Symphony Health database is an administrative claims database and may contain errors or omissions in codes for procedures, diagnoses, or dispensing. Impact of perampanel use on emergency room visits could not be examined, as these were not identified separately in the database and may be included under outpatient or inpatient visits.

Poster presentation number: 5-018
Tuesday, May 7, 2019, 5:30-6:30 p.m.
Inpatient Hospitalizations Rates in Patients Diagnosed with Epilepsy and Treated with Perampanel or Lacosamide
Edward Faught, MD, Xuan Li, MS, Jiyoon Choi, PharmD, MBA, Manoj Malhotra, MD, Russell L. Knoth, PhD

Summary: The retrospective analysis of claims data included 1,717 patients (at least 12 years or older) in each cohort who were treated with perampanel or lacosamide, another antiepileptic drug (AED), (for a total of 3,434 patients) 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. Patients treated with perampanel had a significantly greater reduction in all-cause hospitalizations compared to those treated with lacosamide, (25.3% vs 30.3%; p=0.0010; respectively). A similar result was seen for epilepsy-related hospitalizations, a reduction of 19.6% vs 22.6%; p=0.0376, perampanel and lacosamide, respectively. Among those who had any hospitalization in the baseline period, patients treated with perampanel had a 59.9% reduction in all-cause hospitalizations vs. a 48.6% reduction for those treated with lacosamide (p<0.05). A similar result was seen for epilepsy-related hospitalizations, a reduction of 65% vs 58.9% (p<0.05), respectively. The Symphony Health database is an administrative claims database and may contain errors or omissions in codes for procedures, diagnoses, or dispensing. Because of the limitations of claims data, it was not known if patients were taking the approved dosage of perampanel, if all patients had partial-onset seizures or were receiving perampanel as adjunctive therapy for primary generalized tonic-clonic seizures.

Poster presentation number: 5-002 
Tuesday, May 7, 2019, 5:30-6:30 p.m.
Risk of Hospitalization in Patients with Uncontrolled Epilepsy Treated with a Long Versus Short Half-Life Adjunctive Antiepileptic Medication
Joyce Cramer, BS, Eunice Chang, PhD, Jessie Yan, PhD, Russell L Knoth, PhD, Contessa Fincher, PhD, Manoj Malhotra, MD, Jiyoon Choi, PharmD

Summary:  A retrospective, longitudinal cohort study using the Symphony Health Solution (SHS) Patient Integrated Dataverse to identify 4,984 patients aged ≥12 years and diagnosed with epilepsy between 8/1/2012 to 7/31/2017.  Once identified, patients were stratified into one of two groups based on the index AED half-life. Following stratification, 2,279 were treated with a long half-life (LHL) AED (>20 hours) and 2,705 with a short half-life (SHL) AED (<20 hours). In the one-year follow-up, unadjusted relative risk of hospitalization was lower in the long half-life group vs the short half-life group (0.81, 95% CI: 0.73, 0.89; p<0.001).  After adjusting for group differences, the relative risk of hospitalization for the long half-life group was significantly lower than that of the short half-life group (0.84, 95% CI: 0.76, 0.93]; p=0.0007). The SHS data set only includes inpatient data from 30% of hospitals in the U.S. Patients who were serviced by the hospitals included in the SHS data set could not be differentiated from those with missing data from hospitals outside of the SHS data set to perform the analysis. In conclusion, in patients with uncontrolled epilepsy who were initiated on an adjunctive AED, the choice of an LHL vs SHL AED was associated with a significantly lower risk of hospitalization and the benefits of selecting an LHL AED as adjunctive therapy should be considered for appropriate patients with uncontrolled epilepsy. The observed reduction in utilization would likely reduce cost and improve the economic burden associated with this chronic disease.

Limitations 
These results should be interpreted cautiously. Potential confounders, including changes in background AEDs and the potential association between treatment duration and different tolerability, could have influenced study results. Because of the limitations of claims data, it was not known if patients were taking the approved dosage of perampanel, if all patients had partial-onset seizures or were receiving perampanel as adjunctive therapy for primary generalized tonic-clonic seizures to be consistent with perampanel's approved use.

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.

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.).

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
James Merse
Eisai Inc.
201-746-2979
James_merse@eisai.com

SOURCE Eisai Inc.