The U.S. Food and Drug Administration (FDA) has approved a type of antiangiogenic drug called an mTOR inhibitor to treat a brain tumor disorder related to tuberous sclerosis, a genetic disorder that affects approximately 1 in 6,000 infants and children. Tuberous sclerosis is characterized by benign tumors (hamartomas) that affect multiple organ systems, including the brain, skin, kidneys, lungs, heart, and the retina of the eyes.

Up to 20% of patients with tuberous sclerosis develop benign brain tumors called subependymal giant-cell astrocytomas (SEGA), which frequently cause seizures and somtimes even death. Surgical removal of the tumors is the standard treatment for SEGA, but is often unfeasible due to the location of the tumors in the brain.

Researchers at Cincinnati Children’s Hospital Medical Center enrolled 28 children, aged 3 years and above, with growing SEGAs to receive oral everolimus (Afinitor) at a dose of 3.0 mg per square meter of body surface area. In the study, 32% of patients experienced a reduction of 50% or greater in the size of their largest SEGA at 6 months of follow-up, and 75% (21 patients) had a reduction of tumor volume of at least 30%. No patients developed new tumors during the study, and none required surgery for existing tumors while on treatment. The median duration of everolimus therapy was 21.5 months. Further, a substantial reduction in seizure frequency was observed in 9 of 16 patients who were monitored by video EEG.

mTOR inhibitors, which include everolimus and a similar agent, sirolimus, are antiangiogenic (suppress new blood vessel growth) and also inhibit tumor cell proliferation in certain cancers and in benign tumors in which the mTOR complex of proteins is upregulated. The same research group had previously shown that sirolimus was active in 25 adult patients with benign brain tumors. There is also evidence that mTOR inhibitors may suppress seizures and improve cognitive function independently of shrinking tumors.

The indication for everolimus for SEGA associated with tuberous sclerosis was granted under the FDA’s accelerated approval program, which provides access to therapies that address an unmet medical need pending confirmation in larger clinical trials. The maker of everolimus has initiated a randomized, placebo controlled Phase 3 trial to confirm the results of the initial 28-patient study. The trial involves patients in 10 countries, including Australia, Belgium, Canada, Germany, Italy, the Netherlands, Poland, Russia, the UK and the U.S.