Novartis announced phase III trial results that showed more than one-third of patients taking AfinitorR (everolimus) tablets experienced a 50% or greater reduction in the size of their subependymal giant cell astrocytomas (SEGAs), non-cancerous brain tumors associated with tuberous sclerosis complex (TSC).

Afinitor is approved in the U.S. to treat patients with SEGA associated with tuberous sclerosis who require therapeutic intervention but are not candidates for curative surgical intervention. The effectiveness of everolimus is based on an analysis of change in SEGA volume.

The 117-patient, randomized, placebo-controlled phase III EXIST-1 (EXamining everolimus In a Study of TSC) trial met its primary endpoint of SEGA response rate, with 35% of patients (27 of 78) receiving everolimus experiencing a 50% or greater reduction in SEGA volume (sum of volumes of all target SEGAs) relative to baseline versus 0% of patients (0 of 39) on placebo (p<0.0001).

Everolimus targets mTOR, a protein that acts as a regulator of tumor cell division, blood vessel growth and cell metabolism. Tuberous sclerosis complex is caused by defects in the TSC1 and/or TSC2 genes. When these genes are defective, mTOR activity is increased, causing uncontrolled tumor cell growth and proliferation, blood vessel growth and altered cellular metabolism, leading to the formation of non-cancerous tumors throughout the body, including the brain. By inhibiting mTOR activity in this signaling pathway, everolimus may reduce cell proliferation, blood vessel growth and glucose uptake related to SEGA associated with TSC.

The phase III study supports the findings of the phase II study used for registration in several countries.