WOODCLIFF LAKE, NJ, USA I October 20, 2014 I Eisai Inc. announced today that the U.S. Food and Drug Administration (FDA) accepted for review the company’s Supplemental New Drug Application (sNDA) for its in-house-discovered AMPA receptor antagonist perampanel for the treatment of primary generalized tonic-clonic (PGTC) seizures, a severe form of seizures, in patients 12 years and older. FYCOMPA™ (perampanel) CIII, which was approved by the FDA in October 2012 and became available in January 2014, is currently indicated as an adjunctive treatment for partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy age 12 years and older.
The sNDA was submitted to the FDA on August 19, 2014. Acceptance of the sNDA indicates that the FDA has found the company’s submission to be sufficiently complete to review. “Eisai remains dedicated to advancing epilepsy care for patients, and the acceptance of this sNDA represents an important step toward expanding treatment options for patients whose PGTC seizures are not controlled by their current medication,” said Lynn Kramer, Chief Clinical Officer, President, Neuroscience & General Medicine PCU Eisai Product Creation Systems, Eisai, Inc.
About Primary Generalized Tonic-Clonic Seizures
Epilepsy is a disease of the brain characterized by unprovoked seizures that can affect a variety of mental and physical functions. According to the Institute of Medicine, epilepsy is one of the most common neurological diseases, affecting 2.2 million people in the United States. Generalized seizures account for approximately 40% of all epilepsy, and Primary Generalized Tonic-Clonic (PGTC) seizures are one of the most common and most severe forms of generalized seizures. For the majority of patients, a PGTC seizure begins with a loss of consciousness without any prior warning symptoms and a sudden contraction of the tonic muscles, causing the patient to fall down (tonic phase). This is followed by violent convulsions (clonic phase) until the muscles finally relax, and the patient is left with a disturbance of consciousness. While the seizure generally only lasts a few minutes, the patient often feels confused, groggy or drowsy for a longer period of time before returning to normal.
About FYCOMPA (perampanel)
FYCOMPA is an oral medication and is the first FDA-approved non-competitive AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) glutamate receptor antagonist. Glutamate is the primary excitatory neurotransmitter in the central nervous system. The precise mechanism by which FYCOMPA exerts its antiepileptic effects in humans has not been fully elucidated. FYCOMPA is approved in more than 35 countries.
| |
Important Safety Information
|
|
| |
|
|
| |
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
Hostility- and aggression-related adverse reactions occurred in 12% and 20% of clinical trial patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg/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. 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.
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 or 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 randomized to receive FYCOMPA at doses of 8 mg and 12 mg/day, respectively, compared to 10% of placebo-treated patients. Gait disturbance related events were reported in 12% and 16% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg/day, respectively, compared to 2% of placebo-treated patients. These adverse reactions occurred mostly during the titration phase.
Somnolence and Fatigue
FYCOMPA caused dose-dependent increases in somnolence and fatigue-related events. Somnolence was reported in 16% and 18% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg/day, respectively, compared to 7% of placebo patients. Fatigue-related events were reported in 12% and 15% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg/day, respectively, compared to 5% of placebo patients. In the controlled Phase 3 epilepsy clinical trials, these adverse reactions occurred mostly during the titration phase. 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 randomized to receive FYCOMPA at doses of 8 mg and 12 mg/day, respectively, compared to 3% of placebo-treated patients.
Withdrawal of AEDs
A gradual withdrawal is generally recommended with antiepileptic drugs to minimize the potential of increased seizure frequency.
Most Common Adverse Reactions
In clinical trials, the most frequently reported dose-related adverse reactions in patients receiving FYCOMPA 8 mg or 12 mg vs placebo (>4% and at least 1% higher than the placebo group) included dizziness (36% vs 9%), somnolence (16% vs 7%), fatigue (10% vs 5%), irritability (9% vs 3%), falls (7% vs 3%), nausea (7% vs 5%), ataxia (5% vs 0%), balance disorder (4% vs 1%), gait disturbance (4% vs 1%), vertigo (4% vs 1%), and weight gain (4% vs 1%).
Drug Interactions
FYCOMPA may decrease the efficacy of contraceptives containing levonorgestrel. Plasma levels of FYCOMPA were decreased when administered with carbamazepine, phenytoin and oxcarbazepine. Concomitant use with strong CYP3A inducers such as St. John’s wort and rifampin should be avoided. Multiple dosing of FYCOMPA 12 mg/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 Category C and Lactation
FYCOMPA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 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 a nursing woman.
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 drug substance and has the potential to be abused or lead to drug dependence.
Please see the FYCOMPA (perampanel) CIII Full Prescribing Information
Epilepsy is a therapeutic area of focus for Eisai. The company continues to make further contributions to help address the diversified needs of epilepsy patients and their families as part of its corporate human health care (hhc) mission.
Eisai Inc.
At Eisai Inc., human health care 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 help address unmet medical needs. We are a fully integrated pharmaceutical business with discovery, clinical, manufacturing and marketing capabilities. Our key areas of commercial focus include oncology and specialty care (Alzheimer’s disease, epilepsy and metabolic disorders). To learn more about Eisai Inc., please visit us at www.eisai.com/US.
Eisai Inc. has affiliates that are part of a global product creation organization that includes R&D facilities in Massachusetts, New Jersey, North Carolina and Pennsylvania, as well as a global demand chain organization that includes manufacturing facilities in Maryland and North Carolina. Eisai’s global areas of R&D focus include neuroscience; oncology; metabolic disorders; vascular, inflammatory and immunological reaction; and antibody-based programs.
SOURCE: Eisai
Post Views: 31
WOODCLIFF LAKE, NJ, USA I October 20, 2014 I Eisai Inc. announced today that the U.S. Food and Drug Administration (FDA) accepted for review the company’s Supplemental New Drug Application (sNDA) for its in-house-discovered AMPA receptor antagonist perampanel for the treatment of primary generalized tonic-clonic (PGTC) seizures, a severe form of seizures, in patients 12 years and older. FYCOMPA™ (perampanel) CIII, which was approved by the FDA in October 2012 and became available in January 2014, is currently indicated as an adjunctive treatment for partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy age 12 years and older.
The sNDA was submitted to the FDA on August 19, 2014. Acceptance of the sNDA indicates that the FDA has found the company’s submission to be sufficiently complete to review. “Eisai remains dedicated to advancing epilepsy care for patients, and the acceptance of this sNDA represents an important step toward expanding treatment options for patients whose PGTC seizures are not controlled by their current medication,” said Lynn Kramer, Chief Clinical Officer, President, Neuroscience & General Medicine PCU Eisai Product Creation Systems, Eisai, Inc.
About Primary Generalized Tonic-Clonic Seizures
Epilepsy is a disease of the brain characterized by unprovoked seizures that can affect a variety of mental and physical functions. According to the Institute of Medicine, epilepsy is one of the most common neurological diseases, affecting 2.2 million people in the United States. Generalized seizures account for approximately 40% of all epilepsy, and Primary Generalized Tonic-Clonic (PGTC) seizures are one of the most common and most severe forms of generalized seizures. For the majority of patients, a PGTC seizure begins with a loss of consciousness without any prior warning symptoms and a sudden contraction of the tonic muscles, causing the patient to fall down (tonic phase). This is followed by violent convulsions (clonic phase) until the muscles finally relax, and the patient is left with a disturbance of consciousness. While the seizure generally only lasts a few minutes, the patient often feels confused, groggy or drowsy for a longer period of time before returning to normal.
About FYCOMPA (perampanel)
FYCOMPA is an oral medication and is the first FDA-approved non-competitive AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) glutamate receptor antagonist. Glutamate is the primary excitatory neurotransmitter in the central nervous system. The precise mechanism by which FYCOMPA exerts its antiepileptic effects in humans has not been fully elucidated. FYCOMPA is approved in more than 35 countries.
| |
Important Safety Information
|
|
| |
|
|
| |
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
Hostility- and aggression-related adverse reactions occurred in 12% and 20% of clinical trial patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg/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. 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.
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 or 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 randomized to receive FYCOMPA at doses of 8 mg and 12 mg/day, respectively, compared to 10% of placebo-treated patients. Gait disturbance related events were reported in 12% and 16% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg/day, respectively, compared to 2% of placebo-treated patients. These adverse reactions occurred mostly during the titration phase.
Somnolence and Fatigue
FYCOMPA caused dose-dependent increases in somnolence and fatigue-related events. Somnolence was reported in 16% and 18% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg/day, respectively, compared to 7% of placebo patients. Fatigue-related events were reported in 12% and 15% of patients randomized to receive FYCOMPA at doses of 8 mg and 12 mg/day, respectively, compared to 5% of placebo patients. In the controlled Phase 3 epilepsy clinical trials, these adverse reactions occurred mostly during the titration phase. 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 randomized to receive FYCOMPA at doses of 8 mg and 12 mg/day, respectively, compared to 3% of placebo-treated patients.
Withdrawal of AEDs
A gradual withdrawal is generally recommended with antiepileptic drugs to minimize the potential of increased seizure frequency.
Most Common Adverse Reactions
In clinical trials, the most frequently reported dose-related adverse reactions in patients receiving FYCOMPA 8 mg or 12 mg vs placebo (>4% and at least 1% higher than the placebo group) included dizziness (36% vs 9%), somnolence (16% vs 7%), fatigue (10% vs 5%), irritability (9% vs 3%), falls (7% vs 3%), nausea (7% vs 5%), ataxia (5% vs 0%), balance disorder (4% vs 1%), gait disturbance (4% vs 1%), vertigo (4% vs 1%), and weight gain (4% vs 1%).
Drug Interactions
FYCOMPA may decrease the efficacy of contraceptives containing levonorgestrel. Plasma levels of FYCOMPA were decreased when administered with carbamazepine, phenytoin and oxcarbazepine. Concomitant use with strong CYP3A inducers such as St. John’s wort and rifampin should be avoided. Multiple dosing of FYCOMPA 12 mg/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 Category C and Lactation
FYCOMPA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 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 a nursing woman.
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 drug substance and has the potential to be abused or lead to drug dependence.
Please see the FYCOMPA (perampanel) CIII Full Prescribing Information
Epilepsy is a therapeutic area of focus for Eisai. The company continues to make further contributions to help address the diversified needs of epilepsy patients and their families as part of its corporate human health care (hhc) mission.
Eisai Inc.
At Eisai Inc., human health care 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 help address unmet medical needs. We are a fully integrated pharmaceutical business with discovery, clinical, manufacturing and marketing capabilities. Our key areas of commercial focus include oncology and specialty care (Alzheimer’s disease, epilepsy and metabolic disorders). To learn more about Eisai Inc., please visit us at www.eisai.com/US.
Eisai Inc. has affiliates that are part of a global product creation organization that includes R&D facilities in Massachusetts, New Jersey, North Carolina and Pennsylvania, as well as a global demand chain organization that includes manufacturing facilities in Maryland and North Carolina. Eisai’s global areas of R&D focus include neuroscience; oncology; metabolic disorders; vascular, inflammatory and immunological reaction; and antibody-based programs.
SOURCE: Eisai
Post Views: 31
