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Swissmedic, the Swiss Agency for Therapeutic Products, has approved Votubia® (everolimus) tablets for the treatment of patients aged three years and older, with subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TS), for whom surgery is not a suitable option. Votubia is the first medication approved in Switzerland to treat these patients, who are primarily children and adolescents. In the US, everolimus is approved for patients with SEGA under the trade name Afinitor® tablets.
Tuberous sclerosis is a genetic disorder that may cause benign tumours to form in vital organs and can affect many different parts of the body, most commonly the brain. Signs of TS vary depending on which system and which organs are involved. SEGAs, or benign brain tumours, occur in up to 20% of patients with TS and may lead to a variety of resulting disorders including seizures, swelling in the brain, developmental delays and skin lesions. Prior to this approval, surgery was the only treatment option for Swiss patients with growing SEGAs associated with TS.
The approval is based on a prospective, open-label, single-arm Phase II study of 28 patients. Results showed 75% of patients (21 of 28) experienced a reduction of 30% or greater in the size of their largest SEGA and 32% (nine of 28) experienced a reduction of 50% or greater at six months relative to baseline. Of 16 patients with seizures at the start of the study, nine experienced decreases in seizure frequency, six reported no change and one experienced an increase at six months relative to baseline. Facial angiofibromas (red elevated skin lesions) improved in 87% of patients (13 of 15 evaluated patients) from baseline to six months.
“This approval of Votubia is significant for children and adults who have SEGA associated with tuberous sclerosis and, until now, have had limited treatment options,” said Hervé Hoppenot, President, Novartis Oncology. “This milestone represents our first approval in Europe for Votubia and underscores our commitment to help patients worldwide improve their management of this difficult-to-treat disease.”
Everolimus targets mTOR, a protein that acts as an important regulator of tumour cell division, blood vessel growth and cell metabolism. Tuberous sclerosis is caused by defects in the TSC1 and TSC2 genes. When these genes are defective, mTOR activity is increased, which can cause uncontrolled tumour cell growth and proliferation, blood vessel growth and altered cellular metabolism, leading to the formation of benign tumours throughout the body, including the brain. By inhibiting mTOR activity in this protein pathway, everolimus mayreduce cell proliferation, blood vessel growth and glucose uptake related to SEGA associated with TS.
Regulatory approvals have also been granted in this disease setting in the United States, Brazil, Guatemala and the Philippines. Submissions to the European Medicines Agency (EMA) and other global regulatory agencies are under review.
Tuberous sclerosis affects approximately one to two million people worldwide. In Europe, the prevalence in the general population is estimated to be nearly nine cases per 100,000. SEGAs occur in up to 20% of patients with TS.