The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for Votubia (everolimus) tablets for the treatment of adult patients with renal angiomyolipoma associated with tuberous sclerosis complex (TSC) who are at risk of complications (based on factors such as tumour size or presence of aneurysm, or presence of multiple or bilateral tumours) but who do not require immediate surgery. Votubia would be the first medication available in the European Union (EU) for these patients.
Hervé Hoppenot, President, Novartis Oncology, said, “Today’s positive CHMP opinion for Votubia is important for patients in the EU with TSC, as renal angiomyolipoma is among the most difficult-to-treat manifestations of this debilitating disease. There remain many unmet medical needs in TSC, and Novartis is committed to understanding and improving the lives of people affected by this rare disease through clinical research, education and collaboration with the global TSC community.”
In the EU, the European Commission generally follows the recommendations of the CHMP and delivers its final decision within three months of the CHMP recommendation. The decision will be applicable to all 27 EU member states plus Iceland and Norway. In Europe, everolimus has orphan drug designation for TSC. Orphan drugs are those that treat a condition which affects no more than five in 10,000 people in the EU.
The CHMP positive opinion is based on data from the phase III EXIST-2 (EXamining everolimus In a Study of TSC) trial, which found that 42 per cent of patients on everolimus experienced an angiomyolipoma response versus zero per cent of patients in the placebo arm (p<0.0001). The evidence is based on analysis of change in sum of angiomyolipoma volume. Median time to angiomyolipoma progression was 11.4 months in the placebo arm and was not reached in the everolimus arm (p<0.0001). Among the 97 per cent of patients with skin lesions, one of the key concerns for the majority of patients with TSC, a 26 per cent response rate was seen with everolimus versus zero per cent with placebo (p=0.0002).
Everolimus works by inhibiting mTOR, a protein implicated in many tumor-causing pathways. TSC is caused by defects in the TSC1 and/or 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. According to preclinical studies, by inhibiting mTOR activity in this signaling pathway, everolimus reduces cell proliferation and blood vessel growth.
EP News Bureau