The preclinical discovery and development of brivaracetam for the treatment of focal epilepsy

ABSTRACT

Introduction: Brivaracetam (BRV) is a new AED currently licensed for the adjunctive treatment of adult patients with focal epilepsies. It is a ligand of the ubiquitous synaptic vesicle glycoprotein 2A (SV2A).

Areas covered: This paper covers the preclinical and subsequent clinical development of BRV focusing on the discovery of the SV2A protein as the main target for levetiracetam (LEV) and the main similarities and differences between LEV and BRV in terms of pharmacodynamic and pharmacokinetic properties. Phase II and Phase III studies are also presented and data from post-marketing phase IV studies are discussed.

Expert opinion: The preclinical development of BRV is quite unique and has raised several doubts on current methodologies adopted for AED development, reinforcing the need for new approaches. The preclinical and clinical profile suggest that BRV is potentially an ideal compound in the emergency setting given the rapid onset of action associated with being water soluble and, therefore, available in intravenous formulation. In addition, data from Phase III studies have already suggested that BRV may be effective not only in focal epilepsies but also in generalised syndromes. Further data from special populations such as children and women of child bearing age are urgently needed.

KEYWORDS:

• Brivaracetam
• levetiracetam
• epilepsy
• antiepileptic drugs
• SV2A

Article highlights

• The discovery of the SV2A protein and the subsequent development of BRV have further confirmed the need for new and innovative preclinical models of epilepsy

• The preclinical and clinical profile of BRV suggest that it is probably the ideal AED to be used in an emergency setting but data on treatment of status epilepticus are currently just anecdotal

• Emerging data are suggesting that the overnight conversion from LEV to BRV is not only safe and well tolerated but may provide further benefits in terms of tolerability especially in patients with paradoxical sedation from LEV or behavioural adverse events.

• Data from preclinical and Phase III and IV studies are also suggesting that BRV may be effective also in primary generalised syndromes

• Data from special populations such as children and women of child baring age are urgently needed

This box summarizes key points contained in the article.

Declaration of interest

E Russo has received speaker’s fees from Eisai, Lundbeck and Almirall. M Mula has received consultancy fees from UCB Pharma, Eisai, Bial, Elsevier and has intellectual property rights with Springer Science + Business Media. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This manuscript has not been funded.