New FDA Approval: Fycompa® to Treat Seizures

By: Bhavini Shah, PharmD Candidate c/o 2013

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Fycompa® (perampanel) has received the U.S. Food and Drug Administration (FDA) approval for the adjunctive treatment of partial-onset seizures with or without secondarily generalized seizures in patients with epilepsy aged 12 years and older.¹  The drug, manufactured by Eisai Inc., is already approved for use in Iceland, Norway, and the European Commission.

Epilepsy, sometimes referred to as seizure disorder, is defined by the occurrence of at least two unprovoked seizures separated by 24 hours.²  A seizure is a temporary disturbance in brain function in which groups of nerve cells in the brain signal abnormally and excessively.³  Partial seizures, the most common type of seizure seen in people with epilepsy, affect only a limited or localized area of the brain; however they can quickly spread to other parts of the brain.^2,3

According to the Centers of Disease Control and Prevention (CDC), about two million people in the United States have epilepsy and more than one-third of people with epilepsy experience seizures despite taking current available treatments.³  Fycompa^® is the first and only licensed anti-epileptic drug (AED) to selectively target AMPA receptors, a receptor in the brain which plays a critical role in the spread of epileptic seizures.^1,4,5  This drug reduces neuronal hyperexcitation associated with seizures by targeting glutamate activity at postsynaptic AMPA receptors.^4,5

The approval of Fycompa^® was primarily based on three Phase III studies (304, 305, and 306).  All three studies – which  were multi-center, randomized, double-blind, placebo-controlled, dose-escalation, and parallel group studies – evaluated the efficacy and safety of perampanel compared to a placebo given as adjunctive therapy in patients age 12 years and older with partial-onset seizures.  In the first study, the percentage of patients who experienced a decrease in seizure frequency of at least 50% was 37.6% for patients taking 8 mg Fycompa and 36.1% for patients taking 12 mg Fycompa, compared with 26.4% of patients taking placebo. ⁶  In the second study, 33.3% and 33.9% of patients taking 8 mg and 12 mg Fycompa respectively showed a decrease in seizure frequency of at least 50%, compared with 14.7% of patients taking placebo.⁷  The third study showed a significant decrease in seizure frequency only in patients taking 4 mg and 8 mg Fycompa, but not in patients taking a dose of 2 mg.⁸  These studies demonstrated that Fycompa^® significantly reduced seizure frequency in patients with partial-onset seizures with or without secondarily generalized seizures.^6,7,8

Fycompa^® must be titrated in order to optimize the balance between efficacy and tolerability.⁴  It should be used with caution in elderly, taking into account the drug interaction potential in poly-medicated patients.^6,7,8  Dose adjustment is not required in patients with mild renal impairment; however, dose increases in patients with mild and moderate hepatic impairment should be based on clinical response and tolerability.⁴

Fycompa^® has the benefit of convenient, once-daily dosing at bedtime and is the only third generation partial epilepsy treatment approved to treat adolescents with epilepsy from launch. ⁴   Despite the various benefits, the drug does come with a host of potential side effects.  A boxed warning flags the risks of life-threatening neuropsychiatric side effects including mood changes and other mental disturbances, including aggression, anxiety, and paranoia.⁴  More common side effects include dizziness and weight gain.

SOURCES:

1. FDA approves Fycompa to treat seizures. Avaialable at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm325038.htm. Accessed Dec 27, 2012.
2. Rogers SJ, Cavazos JE. Chapter 65. Epilepsy. In: Talbert RL, DiPiro JT, Matzke GR, Posey LM, Wells BG, Yee GC, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York: McGraw-Hill; 2011. http://www.accesspharmacy.com/content.aspx?aID=7985219. Accessed December 29, 2012.
3. Centers for Disease Control and Prevention: Epilepsy. Available at http://www.cdc.gov/epilepsy/. Accessed Dec 27, 2012.
4. Fycompa [package insert]. Available at: http:// http://www.fycompa.eu/. Accessed Dec 27, 2012.
5. Rogawski MA. Revisiting AMPA receptors as an antiepileptic drug target. Epilepsy Curr. 2011(2);11;56-63.
6. French J, Krauss G, Biton V et al. Adjunctive perampanel for refractory partial-onset seizures; Randomized phase III study 304. Neurology 2012; 79: 589-596.
7. French J, Krauss G, Steinhoff B et al. Evaluation of adjunctive perampanel in patients with refractory partial-onset seizures: Results of a randomized global phase III study 305. Epilepsia 2012
8. Krauss G, Serratosa J, Villanueva V et al.
   Randomized phase III study 306: Adjunctive perampanel for refractory partial-onset seizures. Neurology 2012; 78:1408–1415