Drug Provides Seizure Relief for Patients with Tuberous Sclerosis Complex

Novartis recently announced that the Committee for Medicinal Products for Human Use (CHMP) expressed a positive option regarding everolimus (Votubia) dispersible tablets for use in patients with tuberous sclerosis complex.

Everolimus is indicated for use as an adjunctive treatment for patients age 2 and older who experience refractory partial-onset seizures with or without secondary generalization, according to a press release from Novartis.

If everolimus receives approval from the European Commission, the drug would become the first to gain approval for refractory seizures associated with tuberous sclerosis complex (TSC).

Everolimus inhibits the mTOR protein, which is involved in TSC, where mutations cause increased signaling of the mTOR pathway. Several preclinical studies suggest that increased mTOR activity could potentially play a role in the development of epilepsy in patients with TSC.

The positive opinion was based on safety and efficacy findings from the EXIST-3 clinical trial of everolimus. Results from the phase 3 clinical trial indicate that when used as an adjunctive therapy, everolimus reduced refractory partial-onset seizures linked to TSC compared with placebo, according to Novartis.

Patients as young as 2-years-old were enrolled, and all patients included had refractory partial-onset seizures. In the study, all patients received treatment with 1 to 3 antiepileptic drugs. The researchers discovered the seizure response rate was significantly higher with everolimus low exposure and high exposure compared with placebo.

The median percentage of reduction in seizures was also greater, with a reduction of 29.3% with low exposure and 39.6% with high exposure, according to the press release. A 14.9% reduction in seizure occurrence was seen among the placebo group.

Common adverse events in everolimus treatment groups included stomatitis, diarrhea, pyrexia, nasopharyngitis, and upper respiratory tract infection, Novartis reported.

Typically, the European Commission is in agreement with the CHMP’s recommendation. The final decision will be applicable to all 28 states in European Union (EU) plus Norway and Iceland. The drug has previously been granted orphan drug designation for the treatment of TSC.

If approved, everolimus could provide a novel option for patients with the rare genetic disorder characterized by epilepsy. Everolimus is currently the only non-surgical treatment for benign brain and kidney tumors in patients with TSC, according to Novartis.

Findings from the EXIST-3 study may also be used to support other regulatory findings.

"As refractory seizures are among the most debilitating manifestations of TSC, a new therapy that provides seizure control would be a meaningful advance for these patients in the EU," said Bruno Strigini, CEO of Novartis Oncology. "This CHMP opinion is an important milestone in our longstanding commitment to improving care for patients affected by TSC."