To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: FDA Approves Keppra, Adjunctive Therapy For Epilepsy URL: http://www.pslgroup.com/dg/14D1EA.htm Doctor's Guide December 1, 1999
SMYRNA, GA -- December 1, 1999 -- UCB Pharma, Inc. announced that the United States Food and Drug Administration (FDA) has approved Keppra(TM) (levetiracetam) tablets, an antiepileptic drug indicated as adjunctive therapy (added to other antiepileptic drugs), in the treatment of partial onset seizures in adults with epilepsy. UCB Pharma, Inc. filed the new drug application (NDA) for Keppra with the U.S. FDA on February 1, 1999. Keppra's approval within ten months of NDA submission makes it the fastest antiepileptic drug (AED) approved to date. Keppra pharmacokinetic profile is its most distinctive feature. "Keppra is an important new treatment for the management of epilepsy because treatment is initiated with an effective daily dose (500 mg BID) and it contributes valuable additional seizure control without concern for interactions with concomitantly administered antiepileptic drugs," said Tony Tebbutt, President of UCB Pharma, Inc. Keppra is rapidly absorbed after oral administration and food does not affect the extent of bioavailability. Pharmacokinetics are linear and steady state is achieved after two days of multiple twice daily dosing. Keppra is not protein bound (<10 percent bound) and its metabolism is not liver cytochrome P450 dependent, with sixty-six percent (66 percent) of the dose renally excreted unchanged. Plasma half-life of the medication is approximately 6 to 8 hours but is increased in the elderly (due to age-related decrease in renal function) and in patients with renal impairment. Keppra is unlikely to produce, or be subject to, pharmacokinetic drug interactions. "Keppra represents a significant new treatment option for people with epilepsy who often have to manage a complex treatment regimen," said Dr. Ilo Leppik, an investigator for Keppra studies and Director of Research at MINCEP(R) Epilepsy Care, Minneapolis, Minnesota. "The fact that studies have shown Keppra's recommended starting dose is also an effective daily dose is particularly good news for physicians who frequently have to start medication at a sub-therapeutic level due to troublesome side effects." Globally, epilepsy is the most common neurological disorder of the brain. More than 2.3 million Americans have epilepsy, which is characterized by recurring seizures from excessive electrical activity in the brain. Partial seizures are caused by extreme electrical activity in one hemisphere of the brain and result in a range of symptoms, typically with or without loss of consciousness. Despite the number of treatment options currently available, only about 50 percent of patients can completely control their seizures. 1393 epilepsy patients participated in all phases of Keppra studies. A total of 3347 study participants have taken Keppra sometime during its development. The effectiveness of Keppra as adjunctive therapy in the treatment of partial onset seizures in adults was established in three multi-center, randomized, double-blind, placebo-controlled clinical studies. In these studies, 904 patients both in the United States and Europe, having experienced refractory partial onset seizures for at least two years participated. Patients remained on a steady dose of 1-2 AEDs and still experienced at least four seizures during each four weeks of the baseline period. The three well-controlled clinical studies compared either 1000 mg/day and 3000 mg/day Keppra and placebo, 1000 mg/day and 2000 mg/day Keppra and placebo or 3000 mg/day Keppra and placebo given in equally divided doses twice daily. After the baseline period of 8-12-weeks, patients were randomized to either a Keppra or placebo treatment group. The 16-18-week treatment period consisted of a 4-6-week titration period, followed by a 12-week fixed dose evaluation period, during which concomitant AED regimens were held constant. The primary measure of effectiveness was a between group comparison of the reduction in weekly partial seizure frequency for the entire treatment period. Secondary measurements included the responder rate (incidence of patients with a greater than or equal to 50 percent reduction from baseline in partial onset seizure frequency for the entire treatment period). In all three studies, patients treated with 1000 mg/day, 2000 mg/day or 3000 mg/day of Keppra achieved a statistically significantly greater reduction in weekly seizure frequency of partial onset seizures over placebo. At 1000 mg/day Keppra patients in Study 1 had a 26.1 percent and in Study 2 had a 17.1 percent reduction in partial seizure frequency over placebo. At 2000 mg/day Keppra patients in Study 2 had a 21.4 percent reduction in partial seizure frequency over placebo. At 3000 mg/day Keppra patients in Study 1 had a 30.1 percent and in Study 3 had a 23.0 percent reduction in partial seizure frequency over placebo. The responder rate was statistically significantly greater in patients taking 1000/mg day, 2000 mg/day or 3000 mg/day Keppra when compared to placebo. At 1000 mg/day Keppra patients in Study 1 had a 37.1 percent and in Study 2 had a 20.8 percent responder rate. At 2000 mg/day Keppra patients in Study 2 had a 35.2 percent responder rate. At 3000 mg/day Keppra patients in Study 1 had a 39.6 percent and in Study 3 had a 39.4 percent responder rate. Patients treated with placebo had a 7.4 percent, 6.3 percent, and 14.4 percent responder rate for studies 1, 2, and 3 respectively. In clinical studies, Keppra was generally well tolerated by patients. Keppra use is associated with the occurrence of central nervous system adverse events classified as somnolence and fatigue, coordination difficulties and behavioral abnormalities. In controlled studies, when Keppra was given with other AEDs, the most frequently reported adverse events were somnolence, asthenia (lack or loss of strength), infection and dizziness. Adverse events were usually mild to moderate in intensity. Of these adverse events most appeared to occur predominantly during the first four weeks of treatment. Fifteen percent of patients receiving Keppra and 11.6 percent of patients receiving placebo discontinued therapy or had a dose reduction as a result of an adverse event. Minor, but statistically significant, decreases compared to placebo in total mean RBC count (0.03 x10(6)/mm(2)), mean hemoglobin (0.09 g/dL) and mean hematocrit (0.38 percent) were seen in Keppra treated patients in controlled trials. Because levetiracetam is substantially excreted by the kidney, caution should be taken in dosing patients with moderate and severe renal impairment and patients undergoing hemodialysis. "While effective seizure control remains the primary concern for people with epilepsy, there is also serious interest among clinicians in the side effects and potential drug interactions of medications to manage these seizures," said Dr. Leppik. "An add-on therapy such as Keppra that is effective, generally well tolerated and not associated with drug interactions when used in conjunction with other AEDs will benefit both patients and the physicians who treat them." Keppra 250 mg, 500 mg and 750 mg tablets are expected to be available in U.S. pharmacies in the spring of 2000. Related Link: UCB Pharma, Inc. --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. 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