WOODCLIFF LAKE, N.J., June 25, 2019 /PRNewswire/ -- Eisai Inc. today announced results from its FREEDOM Study (Study 342), a Phase III open-label study conducted in Japan and South Korea evaluating the efficacy and safety of FYCOMPA® (perampanel) CIII as monotherapy in new onset or untreated patients with partial-onset seizures (POS). The data was presented at the 33rd International Epilepsy Congress (IEC) taking place in Bangkok, Thailand.
"Through research and development of compounds in our epilepsy franchise, Eisai is committed to shifting the conversation from seizure control to seizure freedom whenever possible. Results from this first investigation of FYCOMPA as monotherapy in patients with partial-onset seizures are an example of this shift," said Lynn Kramer, MD, Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai Inc. "Data from the FREEDOM study showed a seizure freedom rate of 63% with a 4mg/day dose of FYCOMPA as monotherapy in newly diagnosed or untreated patients with POS."
The study included 89 patients ≥12 years of age with newly diagnosed or untreated epilepsy treated with FYCOMPA. Efficacy analyses were based on a modified intent-to-treat population of 73 patients that entered the maintenance period. The study consisted of a 4-week pre-treatment phase and a 32-week treatment phase (6-week titration period; 26-week maintenance period). The median baseline seizure frequency was two seizures per 12 weeks. During the titration period, patients were given FYCOMPA 2mg/day for 2 weeks which was increased to 4mg/day for 4 weeks. Patients who had no tolerability issues at the end of the titration period started the 4mg/day maintenance period.
Seizure freedom for partial-onset seizures was achieved in 63% of patients (46/73) treated with FYCOMPA at Week 26 (95% CI: 50.9–74.0). Of those patients who had secondarily generalized seizures 65% (n=31/48) were convulsive seizure free. The most common adverse events (occurring in ≥5% of patients) out of 68 patients were dizziness (n=18 [26.5%]), nasopharyngitis (n=9 [13.2%]), somnolence (n=9 [13.2%]) and headache (n=7 [10.3%]).
"When selecting an anti-epileptic drug for my patients, I consider benefits of single pill dosing which can reduce overall pill burden, hopefully making it easier for patients to adhere to their treatment schedule as early as possible while taking into account tolerability," said James Wheless, MD, Chair at the Division of Pediatric Neurology, Le Bonheur Children's Hospital, Memphis, Tennessee. "I am excited to see monotherapy data in newly diagnosed patients. In the FREEDOM Study, the majority of patients taking 4mg per day of FYCOMPA achieved convulsive seizure freedom during the 26-week period."
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.
- The study was open-label and did not include a control arm
- Appropriate multiplicity adjustments were not applied
- This information is descriptive and should be interpreted cautiously
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.
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 the FREEDOM study (Study 342)
Study 342 is a multicenter, uncontrolled, open-label, Phase III single-arm study conducted in Japan and South Korea. The study included 89 patients ≥12 years of age with newly diagnosed or untreated POS patients treated with FYCOMPA. Efficacy analyses were based on a modified intent-to-treat population of 73 patients that entered the maintenance period. The primary endpoint was seizure freedom rate for patients with partial-onset seizures at Week 26 maintenance period. Secondary endpoints evaluate safety and tolerability of perampanel monotherapy in untreated subjects with POS. The study consisted of a 4-week pre-treatment phase and a 32-week treatment phase (6-week titration period; 26-week maintenance period). The median baseline seizure frequency was two seizures per 12 weeks. During the titration period, patients were given FYCOMPA 2 mg/day for 2 weeks which was increased to 4 mg/day for 4 weeks. Patients who had no tolerability issues at the end of the titration period started the 4mg/day maintenance period. Seizure freedom for POS was achieved in 46/73 patients (63.0%; 95% CI: 50.9–74.0) who received FYCOMPA 4 mg/day. Of those patients who had secondarily generalized seizures 65% (n=31/48) were convulsive seizure free. The most common adverse events (occurring in ≥5% of patients) out of 68 patients were dizziness (n=18 [26.5%]), nasopharyngitis (n=9 [13.2%]), somnolence (n=9 [13.2%]) and headache (n=7 [10.3%]).
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
BOXED 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 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.
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.
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, manufacturing 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 and follow us on Twitter and LinkedIn.
SOURCE Eisai Inc.
Type Press Release
Date Released June 25, 2019