Improving Epilepsy Care: XCOPRI’s Effectiveness and Safety

• Cenobamate, marketed as XCOPRI in the US and ONTOZRY in the EU, provides various dosage choices to improve treatment adherence and efficacy. 
• SK Life Science’s cenobamate via its multimodal approach, provides much-needed relief for patients with partial-onset seizures by reducing repetitive neuronal firing and hyperexcitability.

Despite a copious amount of antiepileptics in the current market, a significant percentage of individuals still experience uncontrolled seizures, highlighting the dire need for more responsive therapies. Non-adherence is a major pressing issue, particularly prevalent among individuals grappling with refractory epilepsy. There is a thirst for therapies that not only eliminate or diminish seizures but also exhibit minimal adverse effects, thus enhancing patients’ overall quality of life. 

At the 2024 American Academy of Neurology (AAN) conference, SK Life Science unveiled abstracts shedding light on the characterization of their prospective medication, XCOPRI (cenobamate). The data was presented from studies delving into the comparative bioavailability of the drug when administered intact or crushed tablets via oral ingestion or through a nasogastric tube, evaluating the effectiveness of cenobamate in pediatric patients with intractable focal seizures. Furthermore, a retrospective analysis based on claims was also presented, evaluating the efficacy of cenobamate in mitigating hospitalizations among individuals grappling with focal-onset seizures.

The company presented a poster based on a Phase I study, a randomized, open-label, single-dose, three-way crossover with subjects receiving dose each of cenobamate 200 mg as an intact tablet administered with 240 mL of water. All doses were administered in a fasting state measuring the relative bioavailability of cenobamate 200 mg administered as a crushed tablet, either orally or via nasogastric tube, vs. an intact 200 mg cenobamate tablet. Results supported the administration of cenobamate as a crushed tablet in suspension either orally or via nasogastric tube, providing additional dosing flexibility. Therefore, XCOPRI addresses an unmet need for patients who require alternative dosing methods by offering flexibility and providing additional administration options for healthcare providers managing their care with alternative dosing methods.

Another poster presented data from a study with patients ≤17 years old with a diagnosis of intractable focal seizures and taking ≥1 ASM. The retrospective analysis included 176 patients with intractable focal seizures. Patients’ data were assessed based on their line of therapy (LOT), comparing healthcare utilization outcomes. Results indicated an improvement in the rate of epilepsy-related inpatient days from 5.39 days per year to 4.19 per year and a decrease in epilepsy-related emergency room days from 0.82 days per year to 0.58 per year with cenobamate therapy. These findings suggest that cenobamate is associated with reduced inpatient days and ER visits in pediatric patients with intractable focal epilepsy compared to previous therapies, underscoring the potential utility of cenobamate in this population. 

A post-hoc analysis of a Phase III trial, in patients with uncontrolled focal seizures who were taking 1-3 antiseizure medications suggested that early adjustment of adjunctive ASM dosages, including clobazam, phenytoin, phenobarbital, and lacosamide, were beneficial during cenobamate treatment.

Cenobamate’s precise mechanism driving its therapeutic efficacy remains unknown but it is hypothesized to mitigate repetitive neuronal firing primarily through the inhibition of voltage-gated sodium currents. It also serves as a positive allosteric modulator of the γ-aminobutyric acid (GABA_A) ion channel, enhancing its anti-seizure abilities.

With XCOPRI, SK Life Science has established itself as a significant player in the epilepsy market.  The drug also presents itself as a promising treatment option for pediatric patients with drug-resistant epilepsy, with studies indicating its safety and efficacy in this population. Moreover, the recent US FDA approval of XCOPRI as an oral suspension mixed with water for mouth administration or via a nasogastric tube addresses a major route of administration-related impediment in epilepsy treatment.