Dec 5, 2016
WOODCLIFF LAKE, N.J., Dec. 5, 2016 /PRNewswire/ -- Eisai Inc. announced today new analyses and data on perampanel presented at the 2016 Annual Meeting of the American Epilepsy Society (AES).
Perampanel, marketed as FYCOMPA® CIII, is indicated as an adjunctive therapy for the treatment of partial onset seizures (POS) with or without secondarily generalized seizures and primary generalized tonic-clonic seizures (PGTC) in patients with epilepsy who are 12 years of age and older. Please see Important Safety Information for FYCOMPA, including Boxed WARNING for Serious Psychiatric and Behavioral Reactions, below.
This release discusses investigational data for an FDA-approved product. It is not intended to convey conclusions about efficacy or safety. There is no guarantee that any investigational uses of such product will successfully complete clinical development or gain FDA approval. These data include:
Health care resource utilization before and after perampanel initiation for the treatment of epilepsy in the United States
In this analysis of claims data, researchers retrospectively reviewed a large, nationally representative claims database to assess the impact of perampanel on health care resource utilization (HRU). Patients included in the study were 12 years of age or older, with at least one epilepsy diagnosis, at least one perampanel prescription and six months of clinical activity prior to and after the day the perampanel prescription was dispensed. Using Symphony Health Solutions' Patient Transactional Dataset, a large, nationally representative database, the study identified 2,508 patients that were dispensed at least one perampanel prescription and compared HRU in the post-perampanel period to that in the 180 days prior to perampanel treatment.
Researchers observed that post-perampanel periods were consistently associated with significantly lower rates of all-cause HRU than the pre-perampanel period:
Overall, all cause epilepsy-related hospitalizations and outpatient visits in patients receiving perampanel treatment decreased after initiation of perampanel.
It is important to note that there are some limitations to this analysis, including the following. The database may contain errors or omissions in codes for procedures, diagnosis or dispensing. Additionally, the impact of perampanel use on emergency room visits could not be examined as these are not identified separately in this database, and may be included under outpatient or inpatient visits.
Evaluation of long-term efficacy and safety of adjunctive perampanel: analysis of the open-label extension studies
Following the completion of randomized, double-blind, placebo-controlled Phase II/III studies of perampanel in patients with previously uncontrolled partial onset seizures (POS) with or without secondarily generalized (SG) seizures and primary generalized tonic-clonic seizures (PGTC) despite receiving treatment with 1-3 antiepileptic drugs, patients were eligible to enter four open label extension studies (OLEs) according to their specific seizure diagnosis and trial participation. All OLE studies consisted of a blinded Conversion Period (6-16 weeks across studies) where perampanel dose optimization was achieved (maximum 12 mg/day), followed by a maintenance phase. Patients who had previously received placebo during the double-blind phase were converted to perampanel during the OLE; patients who had previously received perampanel during the double-blind phase continued on perampanel during the OLE.
In this post-hoc, pooled analysis of the four studies of the 858 patients aged 12 years and older with POS with SG seizures (n=720) and patients with PGTC seizures (n=138), the median percent reduction in seizure frequency per 28 days was:
Across the entire perampanel exposure, adverse events were reported in 650 (90.3%) patients with SG seizures and 120 (87.0%) patients with PGTC seizures. A total of 94 patients (13.1%) with SG seizures and 13 patients (9.4%) with PGTC seizures experienced adverse events leading to withdrawal. The most common adverse events occurring in ≥ 10% of patients were dizziness, somnolence, headache, nasopharyngitis, fatigue, irritability, upper respiratory tract infection and vertigo.
Based on this analysis, long-term (up to 4 years) adjunctive treatment with once-daily perampanel (up to 12 mg) appeared to be efficacious and had similar safety and tolerability profiles in patients aged 12 years and older with generalized tonic-clonic seizures, whether SG or PGTC compared with the double-blind studies.
There were 548 patients (76.1%) with SG seizures and 60 patients (43.5%) with PGTC seizures who discontinued perampanel; the most common reasons for discontinuation were administrative/other, subject choice and inadequate therapeutic effect.
Epilepsy is a medical condition that produces seizures affecting a variety of mental and physical functions. According to the Institute of Medicine, epilepsy is one of the most common neurological disorders, which affects 2.9 million people in the United States. Partial-onset seizures are the most common type of seizure seen in people with epilepsy, accounting for 60 percent of all seizures. Generalized seizures account for approximately 40 percent of all epilepsy, with primary generalized tonic-clonic seizures being one of the most common and severe forms of generalized seizures.
About FYCOMPA (perampanel)
FYCOMPA (perampanel) is indicated as adjunctive therapy for the treatment of partial-onset seizures with or without secondarily generalized seizures and primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older.
FYCOMPA is an oral medication and 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.
FYCOMPA has been designated by the U.S. Drug Enforcement Administration as a federally-controlled substance (CIII).
Important Safety Information for FYCOMPA (perampanel) CIII
WARNING: SERIOUS PSYCHIATRIC AND BEHAVIORAL REACTIONS
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. The combination of alcohol and FYCOMPA significantly worsened mood and increased anger. Homicidal ideation and/or threat have also been reported postmarketing in patients treated with FYCOMPA. 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 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 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 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.
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 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.
FYCOMPA may decrease the efficacy of contraceptives containing levonorgestrel.
Plasma levels of FYCOMPA were decreased when administered with carbamazepine, phenytoin, or oxcarbazepine. Concomitant use of FYCOMPA with other strong CYP3A inducers (e.g., rifampin, St. John's wort) should be avoided. 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.
Please see accompanying Full Prescribing Information for FYCOMPA (perampanel), including Boxed WARNING.
You are encouraged to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1‑800‑FDA‑1088.
About Eisai Inc.
At Eisai Inc., human health care (hhc) is our goal. We give our first thoughts to patients and their families, and helping to increase the benefits health care provides. As the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd., we have a passionate commitment to patient care that is the driving force behind our efforts to discover and develop innovative therapies to help address unmet medical needs.
Eisai is a fully integrated pharmaceutical business that operates in two global business groups: oncology and neurology (dementia-related diseases and neurodegenerative diseases). Each group functions as an end-to-end global business with discovery, development, and marketing capabilities. Our U.S. headquarters, commercial and clinical development organizations are located in New Jersey; our discovery labs are in Massachusetts and Pennsylvania; and our global demand chain organization resides in Maryland and North Carolina. To learn more about Eisai Inc., please visit us at www.eisai.com/US.
SOURCE Eisai Inc.
For further information: Media Inquiries, Laurie Landau, Eisai Inc., 201-746-2510; Investor Inquiries, Ivor Macleod, Eisai Inc., 201-746-2660