The European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for Novartis’ Votubia (everolimus) dispersible tablets as an adjunctive therapy for patients, ages 2 and older, whose refractory partial-onset seizures are associated with tuberous sclerosis complex (TSC).
If approved by the European Commission (EC), Votubia would be the first drug approved as an adjunctive treatment for TSC.
“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,” Bruno Strigini, CEO, Novartis Oncology, said in a press release. “This CHMP opinion is an important milestone in our longstanding commitment to improving care for patients affected by TSC.”
CHMP’s opinion was based on data from EXIST-3, a three-arm, randomized, double-blind, placebo-controlled (NCT01713946) clinical trial. The study evaluated the efficacy and safety of two trough-ranges of Votubia as an adjunct therapy in TSC patients who have refractory partial-onset seizures. Results showed that, used in this manner, Votubia could reduce TSC-caused refractory partial-onset seizures compared to placebo.
All the patients in the study were being treated with one to three anti-epileptic drugs (AEDs).
Those also treated with Votubia had a higher seizure response rate (more than 50% reduction) compared to patients treated with placebo, and a greater reduction from baseline in seizure frequency.
The most common side effects observed were nasopharyngitis, stomatitis, fever, diarrhea, and upper respiratory tract infection.
The EC will now review CMPH’s opinion on the drug and issue a final decision.
Votubia targets mTOR, a protein that acts as an important regulator of tumor cell division, blood vessel growth, and cell metabolism. In TSC, hyperactivity in the mTOR pathway leads to increased cellular growth and proliferation, neuronal hyper-excitability, brain abnormalities, and impaired synaptic plasticity. Results from preclinical studies have suggested that hyperactive mTOR activity could play a role in the gradual process by which the brain develops epilepsy in TSC.
Votubia tablets are approved in Europe to treat adults with renal angiomyolipoma associated with TSC, who are at risk of complications but do not need immediate surgery. In the U.S., the drug is available under the brand name Afinitor for this same group of patients.