Phase III of Afinitor (everolimus) shows benefits for tuberous sclerosis complex- Novartis

Novartis announced results from a Phase III study showing Afinitor (everolimus), when used as an adjunctive therapy, significantly reduced treatment-resistant seizures associated with tuberous sclerosis complex (TSC) compared to placebo. Patients in all treatment arms were also taking one to three anti-epileptic drugs (AEDs). In the study, 366 patients with TSC and treatment-resistant seizures were randomized to receive targeted concentrations of everolimus titrated to Low Exposure (LE; 3-7 ng/mL; n=117) or High Exposure (HE, 9-15 ng/mL; n =130), or placebo (n=119). The percentage reduction from baseline in seizure frequency was significantly greater among patients randomized to everolimus LE (29.3%) and HE (39.6%) vs placebo (14.9%).

Seizure response rate (at least 50% reduction) was also significantly greater with everolimus LE (28.2%) and HE (40.0%) vs placebo (15.1%). The most common (at least 20%) adverse events reported with everolimus LE/HE vs placebo included stomatitis (28.2%/30.8% vs 3.4%), mouth ulceration (23.9%/21.5% vs 4.2%), and diarrhea (17.1%/21.5% vs 5.0%). Serious AEs reported were 13.7%/13.8% vs 2.5%. The study, EXIST-3 (EXamining everolimus In a Study of TSC), is being presented during a plenary session at the 68th Annual Meeting of the American Academy of Neurology.

Comment: TSC is a genetic disorder that may cause non-cancerous tumors to form in vital organs, including the kidney and brain. Known as Votubia in the European Union and Switzerland for the treatment of certain patients with TSC, everolimus is the first and only medication for adult patients with these kidney tumors associated with TSC who do not require immediate surgery, and separately for pediatric and adult patients with SEGAs who require therapeutic intervention but are not amenable to surgery.