Novartis' phase-II study show Afinitor (everolimus) tablets is the first medication in a clinical trial to decrease the size of subependymal giant cell astrocytomas (SEGAs), benign brain tumours associated with tuberous sclerosis (TS). In this study of 28 patients presented at the 46th American Society of Clinical Oncology (ASCO) annual meeting in Chicago, 75 per cent of patients experienced a reduction of 30 per cent or greater in the size of their brain tumours from baseline to six months (p<0.001).

Everolimus is approved under the trade name Afinitor (everolimus) tablets for the treatment of patients with advanced renal cell carcinoma whose disease has progressed on or after treatment with vascular endothelial growth factor (VEGF)-targeted therapy.

Tuberous sclerosis is a genetic disorder that causes tumours to form in many vital organs. It is estimated to affect 25,000 to 40,000 people in the US and one to two million worldwide. These tumours can grow in any organ, but typically occur in the brain, kidneys, heart, eyes, lungs and skin. Common symptoms include seizures, mental retardation, autism, behaviour problems and kidney and skin abnormalities.

SEGAs, occurring in 5 to 20 per cent of patients with TS, primarily affect children and adolescents and can cause severe swelling in the brain or hydrocephalus. Currently, the only treatment option for patients with growing SEGAs is brain surgery. Patients enrolled in the study had evidence of established SEGA growth. The data show everolimus significantly decreased the size of SEGAs and no patient required surgery or developed new SEGAs while receiving everolimus.

These data formed the basis for a regulatory submission to the US Food and Drug Administration (FDA) for the treatment of patients with SEGA associated with TS. Everolimus has orphan drug designation for TS in the US. Orphan drugs are those developed to treat diseases affecting fewer than 200,000 people nationally[4],[5].

"Our hope is to offer these patients the first approved medication to treat SEGAs associated with tuberous sclerosis," said Herve Hoppenot, president of Novartis Oncology. "As part of our worldwide everolimus development program, Novartis has launched the EXIST phase-III trial programme to continue to evaluate the impact of everolimus in the fight against tuberous sclerosis."

Tuberous sclerosis is caused by defects in the TSC1 and TSC2 genes that negatively control mTOR, a protein that acts as a central regulator of tumor cell division, blood vessel growth, cell metabolism and cell orientation in neurons. By inhibiting mTOR activity in this protein pathway, everolimus may inhibit tumour growth and resulting symptoms caused by tumour growth in the brain, including hydrocephalus.

In the European Union (EU), everolimus is approved under the trade name Afinitor (everolimus) tablets for the treatment of patients with advanced renal cell carcinoma (RCC) whose disease has progressed on or after treatment with vascular endothelial growth factor (VEGF)-targeted therapy.