CHMP recommends Votubia (everolimus) to treat partial-onset seizures, with or without secondary generalization associated with tuberous sclerosis complex.- Novartis

Novartis announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for Votubia (everolimus) dispersible tablets as an adjunctive treatment of patients aged two years and older whose refractory partial-onset seizures, with or without secondary generalization, are associated with tuberous sclerosis complex (TSC). If approved by the European Commission (EC), Votubia would address an unmet need as currently there are no pharmacologic treatments approved specifically for the treatment of refractory seizures associated with TSC.

The positive CHMP opinion was based on efficacy and safety data from a pivotal Phase III study (EXIST-3: EXamining everolimus In a Study of TSC), which found that when used as an adjunctive therapy, everolimus significantly reduced refractory partial-onset seizures associated with TSC compared to placebo. The youngest patient enrolled was two years of age and patients in all treatment arms received one to three anti-epileptic drugs (AEDs). Seizure response rate (>=50% reduction) was significantly greater with everolimus low exposure (LE) (28.2%, 95% CI 20.3 - 37.3; p=0.008) and high exposure (HE) (40.0%, 95% CI 31.5 - 49.0; p<0.001) vs placebo (15.1%, 95% CI 9.2 - 22.8). The median percentage reduction from baseline in seizure frequency was also significantly greater among patients randomized to everolimus LE (29.3%, 95% CI 18.8 - 41.9; p=0.003) and HE (39.6%, 95% CI 35.0 - 48.7; p<0.001) vs placebo (14.9%, 95% CI 0.1 - 21.7). The most common all-grade adverse events (AEs) of any cause reported during the core phase at frequencies >15% in everolimus LE/HE arms included stomatitis, diarrhea, pyrexia, nasopharyngitis, and upper respiratory tract infection.