SK Life Science, Inc., a global leader in treatments for central nervous system (CNS) disorders and a subsidiary of SK Biopharmaceuticals Co., Ltd., presented data at the American Epilepsy Society (AES) Annual Meeting, showcasing its antiseizure medication XCOPRI® (cenobamate tablets) CV. Key data offered a better understanding of cenobamate’s unique dual mechanism of action (MOA) that enhances GABAergic inhibition at the type A γ-aminobutyric acid (GABAA) ion channel and reduces neuronal excitability by preferentially inhibiting the persistent sodium current.
“We are a company dedicated to advancing treatment options for epilepsy, supporting the epilepsy community and providing meaningful solutions for patients and their families,” said Louis Ferrari, BS, RPh, MBA, vice president, Medical Affairs at SK Life Science. “It is critically important for patients with epilepsy to achieve seizure control as early as possible. The data we presented at AES offer new insights into our drug’s unique dual MOA and highlight the potential for flexible and individualized dosing with cenobamate which, along with adjustment of concomitant ASMs to improve tolerability, may help more patients achieve optimal seizure reduction. Additionally, our data provided objective evidence of our treatment’s effect on patterns of electrical activity in the brain and seizure reduction.”
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Clarification of the MOA of cenobamate
Deeper understanding of cenobamate’s bi-modal mechanism of action further elucidates its dual role on voltage-gated sodium channels and GABAA receptors. Specifically, in preclinical studies, researchers observed cenobamate’s selectivity for blockade of persistent sodium currents (INaP), while sparing the transient sodium current (INaT). The effect of cenobamate’s selective INaP block on the resting membrane potential is augmented by its positive allosteric modulation of GABAA receptor-mediated tonic currents. Cenobamate’s selectivity for the INaP over the INaT likely represents action on the NaV1.6 channel over the NaV1.1 channel, a feature not seen with traditional ASMs, like phenytoin or carbamazepine.
Potential for flexible and individualized dosing
New data examining the initial doses of cenobamate that were associated with seizure freedom in the phase 3 open-label efficacy subset showed the initial seizure freedom interval occurred at a wide range of cenobamate doses, with some patients requiring higher doses. These data highlight the potential for flexible and individualized dosing with cenobamate which, along with adjustment of concomitant antiseizure medication to improve tolerability, may help more patients achieve optimal seizure reduction.
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The effect of cenobamate on responsive neurostimulation epileptiform events
A retrospective, multicenter, observational, 24-week study among 37 patients with uncontrolled seizures, showed a significant reduction in epileptiform events along with a significant reduction in clinically reported seizures during adjunctive cenobamate treatment. Results from this analysis demonstrate, through electrocorticographic data and observation of clinical seizures, the effectiveness of cenobamate in the treatment of focal seizures.
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Source – Prnewswire
