MedicalResearch.com Interview with: Jacqueline French, MD Professor, Department of Neurology Director Translational Research& Clinical Trials Epilepsy NYU Langone Medical Center  MedicalResearch.com: What is the background for this study? Dr. French:  Tuberous sclerosis complex (TSC) is a disease associated with abnormal cell growth, caused by dysfunction of the TSC1 or TSC2 genes and dysruption of the MTOR pathway, which leads to cortical malformations, neuronal hyperexcitability, and seizures. Seizures in patients with TSC often start within the first year of life, and tend not to respond to traditional treatments. Everolimus is a marketed drug that has been used to treat other manifestations of TSC (including giant cell tumors of the brain, renal angiomyolipomas, and angiofibromas of the skin). This study was a placebo-controlled add-on study of everolimus for the treatment of refractory seizures in children and adults with epilepsy.Following an 8-week baseline phase, patients aged 2-65 years (stratified by age) with TSC and refractory seizures on 1-3 antiepileptic drugs were randomized to EVE LT or HT C_min target ranges or placebo, and treated in an 18 week Core Phase (6-wk titration + 12-wk maintenance). Primary endpoints were change from baseline in average weekly frequency of TSC-seizures (seizures not previously shown to be generalized in onset by EEG), expressed as response rate (≥50% reduction [RR]), and percentage reduction. MedicalResearch.com: What are the main findings? Dr. French:  Overall, 366 patients were randomized to EVE LT (n=117), HT (n=130), or placebo (n=119). The median percentage reduction in TSC-seizures was significantly greater with EVE LT (29.3%, P=0.003) and HT (39.6%, P<0.001) vs placebo (14.9%). RR was also significantly greater with EVE LT (28.2%, P=0.008) and HT (40%, P<0.001) vs placebo (15.1%). The most frequent ≥10% all grade adverse events (AEs) reported with EVE LT/HT vs placebo included stomatitis (28.2%/30.8% vs 3.4%), diarrhea (17.1%/21.5% vs 5%), mouth ulceration (23.9%/21.5% vs 4.2%), nasopharyngitis (13.7%/16.2% vs 16%), upper respiratory tract infection (12.8%/15.4% vs 12.6%), aphthous ulcer (4.3%/14.6% vs 1.7%), and pyrexia (19.7%/13.8% vs 5%). Discontinuations due to AEs (5.1%/3.1% vs 1.7%) were low. (more…)