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).

Tuberous Sclerosis Complex is a rare genetic disorder affecting up to one million people worldwide and everolimus is the only approved non-surgical option indicated for treating non-cancerous brain and kidney tumors in certain patients with TSC. EXIST-3 study results show that everolimus is the first adjunctive therapy to achieve clinically significant seizure control in TSC patients and will be the basis for discussion with health authorities worldwide.

Everolimus works by inhibiting the mammalian target of rapamycin (mTOR), a protein that regulates multiple cellular functions. TSC is caused by mutations in the TSC1 or TSC2 genes, resulting in hyperactive signaling of the mTOR pathway which can lead to increased cellular growth and proliferation, neuronal hyper-excitability, abnormalities in cortical architecture and network function and impaired synaptic plasticity.

Pre-clinical research suggests that hyperactive mTOR activity may influence several mechanisms of epileptogenesis, the gradual process by which the brain develops epilepsy.

Tuberous sclerosis complex may cause non-cancerous tumors to form in vital organs including the brain, kidney, heart, lungs and skin, as well as resulting disorders such as epilepsy, autism, cognitive impairment, behavioral problems and psychiatric disorders.