USL255 extended-release topiramate for the treatment of epilepsy

Abstract

USL255 is a once-daily, extended-release formulation of the well-established antiepileptic drug topiramate that was recently approved by the US FDA. As a capsule formulation, USL255 can be swallowed intact or opened and sprinkled onto soft food for patients with swallowing difficulties, including children (≥2 years old) and older patients. USL255 has been evaluated in seven key Phase I and III studies. Compared with immediate-release topiramate taken twice daily, once-daily USL255 provides equivalent topiramate exposure with a 26% reduction in plasma fluctuations. A multinational, Phase III, randomized, double-blind, placebo-controlled clinical trial in patients with refractory partial-onset seizures (PREVAIL) demonstrated that USL255 (200 mg/day) significantly improved seizure control and clinical outcomes versus placebo. USL255 is generally safe and well-tolerated, with a low incidence of neuropsychiatric and neurocognitive adverse events. These data suggest that USL255 may provide a useful treatment option for seizure control with convenient once-daily dosing.

Keywords::

• antiepileptic drug
• extended-release
• Lennox–Gastaut syndrome
• partial-onset seizure
• pediatric
• primary generalized tonic-clonic

Financial and competing interests disclosure

S Chung has served as a consultant for UCB Pharma, Lundbeck, SK Life Science, Upsher-Smith and Neuronex; is a member of a speaker’s bureau for Eisai, UCB Pharma, Lundbeck, Supernus and Sunovion; and has grant/research support through Valeant, Schwarz Pharma, UCB Pharma, Supernus, Eisai, Lundbeck, Medtronics, Upsher-Smith and SK Life Science. M Johnstone and J Benjamin from Prescott Medical Communications Group (Chicago, IL) provided assistance with manuscript drafting and editing, funded by Upsher-Smith Laboratories, Inc. The author has 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.

Key issues

• Topiramate is a broad-spectrum, well-studied antiepileptic drug that has been available in the USA since 1996.

• USL255 is an extended-release formulation of topiramate that was recently approved by the US FDA as initial monotherapy in patients ≥10 years of age with partial-onset seizures (POS) or primary generalized tonic-clonic seizures and as adjunctive therapy in patients ≥2 years of age with POS, primary generalized tonic-clonic seizures or seizures associated with Lennox-Gastaut syndrome.

• USL255 provides convenient once-daily topiramate dosing (vs the twice-daily dosing of immediate-release topiramate), which may increase adherence and reduce plasma concentration fluctuations, which may in turn mitigate some adverse effects associated with peak and trough plasma topiramate levels.

• Phase III data demonstrate that USL255 is effective for refractory POS and is generally well tolerated, with a low rate of cognitive and psychiatric side effects.

• USL255 is available as a capsule that can be swallowed intact or opened and sprinkled on a small amount of soft food for patients with swallowing difficulties (e.g., children and elderly).

Notes