Abstract
Brivaracetam (Briviact®), a 4-n-propyl analogue of levetiracetam developed by UCB Pharma, has been approved in the EU as an adjunctive therapy for the treatment of partial-onset seizures. Brivaracetam binds to synaptic vesicle glycoprotein 2a (SV2A) in the brain with greater selectivity and 15- to 30-fold higher affinity than levetiracetam, as demonstrated in preclinical models, and has demonstrated efficacy in reducing the frequency of partial onset seizures in clinical trials. This article summarizes the milestones in the development of brivaracetam leading to this first approval for use as adjunctive therapy for uncontrolled partial-onset seizures in adults with epilepsy.
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References
Gillard M, Fuks B, Leclercq K, et al. Binding characteristics of brivaracetam, a selective, high affinity SV2A ligand in rat, mouse and human brain: relationship to anti-convulsant properties. Eur J Pharmacol. 2011;664(1):36–44.
UCB. UCB’s new epilepsy drug BRIVIACT® receives EU approval [media release]. 2016. http://www.ucb.com. Accessed 25 Jan 2016.
European Medicines Agency. Briviact (brivaracetam): summary of product characteristics. 2016. http://www.ema.europa.eu. Accessed 10 Feb 2016.
UCB S.A. CHMP recommends EU approval for UCB’s new drug brivaracetam for people with epilepsy [media release]. 2015. http://www.ucb.com. Accessed 25 Jan 2016.
Matagne A, Margineanu DG, Kenda B, et al. Anti-convulsive and anti-epileptic properties of brivaracetam (ucb 34714), a high-affinity ligand for the synaptic vesicle protein, SV2A. Br J Pharmacol. 2008;154(8):1662–71.
Nicolas JM, Hannestad J, Holden D, et al. Brivaracetam, a selective high-affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action. Epilepsia. 2016;57(2):201–9.
Rolan P, Sargentino-Maier ML, Pigeolet E. The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after multiple increasing oral doses in healthy men. Br J Clin Pharmacol. 2008;66:71–5.
Sargentini-Maier ML, Sokalski A, Boulanger P, et al. Brivaracetam disposition in renal impairment. J Clin Pharmacol. 2012;52(12):1927–33.
Stockis A, Sargentini-Maier ML, Horsmans Y. Brivaracetam disposition in mild to severe hepatic impairment. J Clin Pharmacol. 2013;53(6):633–41.
Stockis A, Chanteux H, Rosa M, et al. Brivaracetam and carbamazepine interaction in healthy subjects and in vitro. Epilepsy Res. 2015;113:19–27.
Stockis A, Kruithof AC, Van Gerven JM, et al. Interaction study between brivaracetam and ethanol in healthy subjects [abstract no. 2.307]. Epilepsy Curr. 2015;15(Suppl 1):332.
Stockis A, Watanabe S, Fauchoux N. Interaction between brivaracetam (100 mg/day) and a combination oral contraceptive: a randomized, double-blind, placebo-controlled study. Epilepsia. 2014;55(3):e27–31.
Ryvlin P, Werhahn KJ, Blaszczyk B, et al. Adjunctive brivaracetam in adults with uncontrolled focal epilepsy: results from a double-blind, randomized, placebo-controlled trial. Epilepsia. 2014;55(1):47–56.
Biton V, Berkovic SF, Abou-Khalil B, et al. Brivaracetam as adjunctive treatment for uncontrolled partial epilepsy in adults: a phase III randomized, double-blind, placebo-controlled trial. Epilepsia. 2014;55:57–66.
Pack AM. Brivaracetam, a novel antiepileptic drug: Is it effective and safe? Results from one phase III randomized trial. Epilepsy Curr. 2014;14(4):196–8.
Klein P, Schiemann J, Sperling MR, et al. A randomized, double-blind, placebo-controlled, multicenter, parallel-group study to evaluate the efficacy and safety of adjunctive brivaracetam in adult patients with uncontrolled partial-onset seizures. Epilepsia. 2015;56(12):1890–8.
Beydoun A, Semah F, Villanueva V, et al. Efficacy of brivaracetam stratified according to pathological substrate: findings from a phase 3 clinical trial [abstract no. 2.253]. In: 69th Annual Meeting of the American Epilepsy Society; 2015.
Quarato PP, Whitesides J, D’Souza J, et al. Efficacy and safety of adjunctive brivaracetam for partial-onset (focal) seizures: pooled results from three fixed-dose, randomised, double-blind, placebo-controlled phase III studies. Epilepsia. 2015;56(Suppl 1):208.
Kwan P, Trinka E, Van Paesschen W, et al. Adjunctive brivaracetam for uncontrolled focal and generalized epilepsies: results of a phase III, double-blind, randomized, placebo-controlled, flexible-dose trial. Epilepsia. 2014;55(1):38–46.
French JA, Costantini C, Brodsky A, et al. Adjunctive brivaracetam for refractory partial-onset seizures: a randomized, controlled trial. Neurology. 2010;75(6):519–25.
Van Paesschen W, Hirsch E, Johnson M, et al. Efficacy and tolerability of adjunctive brivaracetam in adults with uncontrolled partial-onset seizures: a phase IIb, randomized, controlled trial. Epilepsia. 2013;54(1):89–97.
Yates SL, Fakhoury T, Liang W, et al. An open-label, prospective, exploratory study of patients with epilepsy switching from levetiracetam to brivaracetam. Epilepsy Behav. 2015;52:165–8.
UCB. UCB announces US and EU regulatory filings for the investigational antiepileptic drug brivaracetam [media release]. 2015. http://www.ucb.com. Accessed 21 Jan 2016.
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The preparation of this review was not supported by any external funding. During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the author on the basis of scientific completeness and accuracy. A. Markham is a contracted employee of Adis, Springer SBM.
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Markham, A. Brivaracetam: First Global Approval. Drugs 76, 517–522 (2016). https://doi.org/10.1007/s40265-016-0555-6
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DOI: https://doi.org/10.1007/s40265-016-0555-6