According to an assessment report released by the EMA last month, the EMA reviewed clinical data on cenobamate—marketed in Europe under the brand name “Ontozry”—for use in children and adolescents. This data comes from a Phase 3 clinical trial in which cenobamate was administered in combination with existing antiepileptic drugs and compared to a placebo group. A total of 169 participants took part in the trial, of whom 34 were adolescents aged 12 to under 18.
The trial was conducted on patients who had experienced at least five PGTC seizures during a 12-week pre-observation period. Participants continued their existing treatment while receiving either cenobamate or a placebo as an adjunct.
Analysis of the subgroup of 34 adolescents showed that during the maintenance period, 15 out of 18 patients (83.3%) in the cenobamate group and 10 out of 16 patients (62.5%) in the placebo group experienced a reduction in seizure frequency of at least 50% compared to baseline. The median reduction in seizure frequency during the double-blind treatment period was also higher in the cenobamate group (79.62% among 18 patients) than in the placebo group (63.71% among 16 patients). However, no statistically significant differences were observed for either metric. The respective p-values were 0.1693 and 0.1762.
In contrast, in the overall patient population, the cenobamate group showed significant improvement compared to the placebo group in regional outcome measures. The median 28-day reduction in seizure frequency—the primary outcome measure in the United States and other regions—was 71.9% in the cenobamate group and 39.6% in the placebo group, representing a statistically significant difference (p=0.0034). The “proportion of patients with a ≥50% reduction in seizure frequency during the maintenance period”—the primary endpoint in Europe, South Africa, Australia, and New Zealand—also showed a statistically significant difference, at 71.1% and 51.3%, respectively (p=0.0099).
Consequently, the EMA determined that while a trend toward improved efficacy was observed in the adolescent subgroup, these results alone were insufficient to support the indication for using cenobamate in combination with existing treatments for adolescent patients with PGTC. The agency explained that the clinical trial was designed to evaluate efficacy across the entire patient population and was not large enough to separately demonstrate efficacy in the adolescent patient group.
The company that submitted the clinical data is Angelini Pharma, a partner that holds the European commercialization rights for cenobamate. Angelini Pharma acquired the European rights to cenobamate from SK BIOPHARMACEUTICALS and markets it under the brand name “Ontozri.” At the time Angelini Pharma submitted the clinical data, it stated that it would not apply for an expansion of the pediatric indication based on that data. Although the EMA also concluded that no changes to the product information or separate regulatory measures were necessary, this stands in contrast to the trend in other countries where procedures for expanding indications are continuing.
An SK BIOPHARMACEUTICALS official stated, “Since this is a matter handled by our partner in Europe, the decision on whether to expand the indication rests with them,” adding, “We are currently proceeding with the application in the U.S. The PGTC and pediatric partial seizures are separate issues, and the FDA and EMA will each make their own independent determinations.”
In fact, two separate applications for indication expansion have been filed in the U.S. Last month, SK BIOPHARMACEUTICALS submitted an application to the U.S. Food and Drug Administration (FDA) to expand the age range for cenobamate—an existing treatment for adult partial-onset seizures—to include pediatric patients. This month, the company also filed an application to add an indication for the treatment of PGTC patients aged 12 and older.
Notably, the clinical trial that served as the basis for the pediatric partial-seizure application was conducted separately from the PGTC clinical trial included in the EMA assessment report. A multinational Phase 3 clinical trial involving 154 patients aged 2 to 17 was registered as completed last month. In announcing the U.S. FDA submission, SK BIOPHARMACEUTICALS stated that it had confirmed the drug’s safety in the pediatric partial-seizure clinical trial. In addition, the company is separately developing an oral suspension for patients who have difficulty swallowing tablets and submitted a New Drug Application (NDA) for this formulation to the FDA in March.
In Japan, partner company Ono Pharmaceutical received approval for cenobamate as a treatment for partial seizures in adults last September. Ono Pharmaceutical is also conducting a Phase 3 clinical trial for pediatric partial seizures and a Phase 3 PGTC clinical trial for adolescents and adults.
The expansion of cenobamate’s age range and indications aligns with SK BIOPHARMACEUTICALS’ product growth strategy. The company is reinvesting the revenue from cenobamate sales in the U.S. into new drug development and the introduction of new products. In the third quarter of this year, U.S. sales of cenobamate reached $156.81 million (approximately 223.6 billion won). SK BIOPHARMACEUTICALS has identified expanding the age range to include pediatric partial seizures, adding the PGTC indication, and developing an oral suspension as key strategies for managing the product’s lifecycle.
A biotech industry official stated, “Although statistical significance could not be confirmed for the adolescent subgroup due to the small number of patients, since this is still separate from an application for expanded indications, it is unlikely that Angelini Pharma has completely ruled out the possibility of applying for expanded indications in the future,” adding, “Since a related application has been filed in the U.S., we need to wait and see how the FDA rules on it.”
