Efficacy and safety of adjunctive everolimus for treatment-resistant focal onset seizures in tuberous sclerosis according to age: insights from EXIST-3 (P3.146)

Objective: To evaluate efficacy and safety of everolimus (EVE) 3–7 (low exposure [LE]) or 9–15 ng/mL (high exposure [HE]) targeted trough concentration (C min ) ranges vs placebo as adjunctive therapy in patients with treatment-resistant seizures associated with tuberous sclerosiscomplex (TSC), according to age categories ( Background: Epileptic seizures are the most common neurological symptoms affecting up to 80–85% of patients with TSC. EVE is shown to improve seizures in TSC. We report the treatment outcomes of epilepsy in pediatric subset of EXIST-3. Design/Methods: Patients aged 2–65 years with TSC and ≥16 treatment-resistant seizures on a stable regimen of 1–3 antiepileptic drugs were randomized to receive EVE LE or HE or placebo. The primary endpoint, which was met and previously reported, was change from baseline in seizure frequency during the maintenance period, expressed as response rate (RR, ≥50% reduction), and median percentage reduction (PR) in seizure frequency. Results: Among 366 patients,117 were randomized to EVE LE, 130 to HE, and 119 to placebo. Majority of the patients were pediatric (81.7%; Conclusions: Adjunctive EVE therapy improved seizure frequency across all age categories, markedly improved with HE in patients Study Supported by: Novartis Pharmaceuticals Disclosure: Dr. Roberts has received personal compensation for activities with Livanova as a speaker. Dr. Kuperman has nothing to disclose. Dr. Koenig has nothing to disclose. Dr. Wu has received personal compensation for activities with Tuberous Sclerosis Alliance, Novartis, Lundbeck Research USA, Inc., the Department of Defense, and the National Institutes of Health. Dr. Wu has received research support with Novartis. Dr. Kohrman has received personal compensation for activities with Novartis. Dr. Kohrman has received research support from Novartis and Upsher-Smith. Dr. Curatolo has received personal compensation for activities with Shire and Novartis as an Advisory Board member. Dr. Nabbout has received personal compensation for activities with Novartis, GW Pharma, Zogenix, Shire, and Eisai. Dr. Berkowitz has received personal compensation for activities with Novartis Pharmaceuticals as an employee. Dr. Herbst has received personal compensation for activities with Novartis as an employee. Dr. Herbst holds stock and/or stock options in Novartis. Dr. Ridolfi has received personal compensation for activities with Novartis as an employee. Dr. Franz has received personal compensation for activities with Novartis for travel support or honoraria or as a consultant.