Brivaracetam is an analog of levetiracetam with a much higher binding affinity to the SV2 synaptic vesicle protein than levetiracetam. The drug showed strong efficacy in Phase II clinical trials evaluating patients with medically refractory partial onset seizures. UCB Pharma has now announced mixed results from two large Phase III clinical trials that evaluated a range of brivaracetam doses for adjunctive treatment of drug-resistant partial-onset seizures. One large pivotal study (N01253) conducted in North America (US, Canada, Mexico), Brazil and Australia compared 5 mg, 20 mg and 50 mg/day doses with placebo. This study showed brivaracetam significantly reduced the number of partial-onset seizures compared to placebo. A second large pivotal study (N01252) conducted in Europe (including Poland and Hungary) and India compared 20 mg, 50 mg and 100 mg/day doses of brivaracetam to placebo; this study, however, failed to reach its primary efficacy endpoint. A third large study conducted in Asia, Europe (including Russia and Ukraine) and South Africa compared safety and tolerability of doses of brivaracetam up to 150 mg/day with placebo for treating partial or generialized seizure types in adults. This study demonstrated the safety of brivaracetam treatment over 16 weeks, but did not assess efficacy as a primary endpoint. Overall, these studies demonstrate that additional studies and analysis are needed to determine which patients might benefit from treatment with brivaracetam.

REFERENCES:

N01253
Double-Blind, Parallel-Group, Placebo Controlled, Safety and Efficacy Study of Adjunctive Brivaracetam in Subjects (>= 16 to 70 Years Old) With Partial Onset Seizures
UCB PBO, 5 mg, 20 mg and 50 mg
http://clinicaltrials.gov/ct2/show/study/NCT00464269?show_locs=Y#locn
Inclusion partial onset seizures, male or female between 16 and <70 years, no more than 2 concomitant AEDs. Study locations: US, Canada, Mexico, Brazil and Australia.

N01252
Double-Blind, Parallel-Group, Placebo Controlled, Safety and Efficacy Study of Adjunctive Brivaracetam in Subjects (>= 16 to 70 Years Old) With Partial Onset Seizures
Doses: PBO, 20 mg BID, 50 mg BID, 100 mg BID
http://clinicaltrials.gov/ct2/show/NCT00490035
Inclusion: male or female between 16 and <70 years, partial epilepsy, 2 concomitant AEDs. Study locations: Europe (including Poland and Hungary), India

by Gregory Krauss, M.D.
Editor: Joseph I. Sirven, M.D.
Submitted: 4/28/09

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Authored Date: 
04/2009