The FINANCIAL — Novartis received approval from the European Commission for Votubia tablets for the treatment of adult patients with renal angiomyolipoma associated with tuberous sclerosis complex who are at risk of complications but who do not require immediate surgery.
This marks the first approval of a medical treatment in this patient population in Europe.
"Renal angiomyolipomas affect the vast majority of patients with TSC and over time can cause debilitating symptoms, a decline in renal function, and possibly even the need for kidney transplant or dialysis," said Dr. Chris Kingswood, Royal Sussex County Hospital, Brighton, United Kingdom. "This approval represents a major advance in the treatment of the disease in Europe, giving clinicians a non-surgical option to manage TSC kidney tumors."
This approval is based on data from the Phase III EXIST-2 trial, which found that 42% of patients taking everolimus experienced an angiomyolipoma response versus 0% of patients in the placebo arm. The evidence is based on analysis of the change in the sum of the angiomyolipoma volume. Median time to angiomyolipoma progression was 11.4 months in the placebo arm and was not reached in the everolimus arm .
"For the first time, European patients living with renal angiomyolipoma associated with TSC now have an effective non-surgical option," said Hervé Hoppenot, President, Novartis Oncology. "This approval reinforces the potential of Votubia to treat a wide range of manifestations associated with TSC, a debilitating, lifelong disease where there remains critical unmet need."
Up to 80% of patients with TSC, a genetic disorder that may cause non-cancerous tumors to form in vital organs, develop renal angiomyolipomas. Typical onset occurs between the ages of 15 and 30 and prevalence increases with age. Over time, these kidney tumors may grow large enough to cause severe internal bleeding, require emergency surgical interventions, such as embolization and nephrectomy, and lead to kidney failure or cardiovascular diseases. As Novartis reported, the tumors can be difficult to manage as they may be numerous and often form in both kidneys. In the EU, approximately 7,000 TSC patients have large growing renal tumors (>3 cm) at risk of bleeding.
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 and can cause uncontrolled tumor 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.
This EC approval follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) adopted for Votubia in September 2012 for the treatment of renal angiomyolipoma associated with TSC and applies to all 27 EU member states, plus Iceland and Norway.
