Log in

Brivaracetam: First Global Approval

  • AdisInsight Report
  • Published:
Drugs Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price includes VAT (Germany)

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. 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.

    Article  CAS  PubMed  Google Scholar 

  2. UCB. UCB’s new epilepsy drug BRIVIACT® receives EU approval [media release]. 2016. http://www.ucb.com. Accessed 25 Jan 2016.

  3. European Medicines Agency. Briviact (brivaracetam): summary of product characteristics. 2016. http://www.ema.europa.eu. Accessed 10 Feb 2016.

  4. 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.

  5. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. 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.

    Article  CAS  PubMed  Google Scholar 

  7. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sargentini-Maier ML, Sokalski A, Boulanger P, et al. Brivaracetam disposition in renal impairment. J Clin Pharmacol. 2012;52(12):1927–33.

    Article  CAS  PubMed  Google Scholar 

  9. Stockis A, Sargentini-Maier ML, Horsmans Y. Brivaracetam disposition in mild to severe hepatic impairment. J Clin Pharmacol. 2013;53(6):633–41.

    Article  CAS  PubMed  Google Scholar 

  10. Stockis A, Chanteux H, Rosa M, et al. Brivaracetam and carbamazepine interaction in healthy subjects and in vitro. Epilepsy Res. 2015;113:19–27.

    Article  CAS  PubMed  Google Scholar 

  11. 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.

    Google Scholar 

  12. 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.

    Article  CAS  PubMed  Google Scholar 

  13. 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.

    Article  CAS  PubMed  Google Scholar 

  14. 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.

    Article  CAS  PubMed  Google Scholar 

  15. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  16. 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.

    Article  CAS  PubMed  Google Scholar 

  17. 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.

  18. 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.

    Google Scholar 

  19. 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.

    Article  CAS  PubMed  Google Scholar 

  20. 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.

    Article  CAS  PubMed  Google Scholar 

  21. 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.

    Article  PubMed  Google Scholar 

  22. 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.

    Article  PubMed  Google Scholar 

  23. 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.

Download references

Disclosure

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Anthony Markham.

Additional information

This profile has been extracted and modified from the AdisInsight database. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch and beyond.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Markham, A. Brivaracetam: First Global Approval. Drugs 76, 517–522 (2016). https://doi.org/10.1007/s40265-016-0555-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-016-0555-6

Keywords

Navigation