Results presented at American Academy of Neurology will be discussed with health authorities for potential worldwide regulatory filings
Novartis has announced the results from a phase III study showing Afinitor (everolimus), when used as an adjunctive therapy, significantly reduces 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). The study, EXIST-3, was presented during a plenary session at the 68th Annual Meeting of the American Academy of Neurology (AAN).
In the study, 366 patients with TSC and treatment-resistant seizures were randomised 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).
TSC 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 tumours 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.
EP News Bureau – Mumbai