FDA approves Novartis’ Afinitor for treatment of renal angiomyolipomas and TSC

Novartis Pharmaceuticals Corporation ("Novartis") announced today that the US Food and Drug Administration (FDA) approved Afinitor® (everolimus) tablets for the treatment of adult patients with kidney tumors known as renal angiomyolipomas and tuberous sclerosis complex (TSC), who do not require immediate surgery. This marks the first approval of a medical treatment in this patient population.

The accelerated approval was based on the Phase III EXIST-2 (EXamining everolimus In a Study of TSC) trial, which found that 42% of patients on everolimus experienced an angiomyolipoma response versus 0% of patients in the placebo arm (p<0.0001). The time to angiomyolipoma progression was also statistically significantly longer in patients on everolimus (p<0.0001).  Among the 97% of trial patients with skin lesions, one of the key concerns for the majority of patients with TSC, a 26% response rate was seen with everolimus versus 0% with placebo.             

"Renal angiomyolipomas are one of the greatest causes of morbidity and mortality in adult TSC patients and can be one of the most challenging aspects of the disease to treat," said John Bissler, MD, Clark D. West Endowed Chair of Nephrology at Cincinnati Children's Hospital Medical Center. "Today marks an important step for the TSC community, as Afinitor is now the only approved medicine to reduce the kidney tumor burden in these patients."

Up to 80% of patients with TSC, a genetic disorder that may cause non-cancerous tumors to form in vital organs, will develop renal angiomyolipomas. Typical onset occurs between the ages of 15 and 30 and prevalence increases with age. Over time, these tumors may grow large enough to cause severe internal bleeding, require emergency surgical interventions, such as embolization and nephrectomy, or lead to kidney failure. The tumors can be difficult to manage as they often form in both kidneys. In addition, skin lesions occur in more than 90% of patients with TSC. They may develop in infancy, can become more prevalent with age and cause disfigurement.

"With this FDA approval, Afinitor becomes the first medical option to treat two of the most debilitating manifestations of this challenging, lifelong disease – kidney tumors called renal angiomyolipomas and brain tumors known as SEGAs," said Herve Hoppenot, President, Novartis Oncology. "This approval further strengthens our commitment to address unmet needs in TSC as we continue to research everolimus and mTOR inhibition across other manifestations of the disease."

Based on an effect on a clinical endpoint other than survival or irreversible morbidity, this indication was approved under the FDA's accelerated approval program, which provides patients access to a treatment for a serious or life-threatening illness and provides meaningful therapeutic benefits to patients over existing treatments. Novartis previously received approval for everolimus for the treatment of adult and pediatric patients, aged three or older, with subependymal giant cell astrocytoma (SEGA) associated with TSC who require therapeutic intervention but are not candidates for curative surgical resection, in the US and in more than 40 additional countries. Filings for renal angiomyolipoma are under way in multiple countries outside of the US.

Afinitor 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 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.