The FDA has approved Novartis’ Afinitor DISPERZ® (everolimus tablets for oral suspension), for the adjunctive treatment of adult and pediatric patients aged two years and older with tuberous sclerosis complex (TSC)-associated partial-onset seizures. 

Afinitor DISPERZ is now the first approved pharmacologic therapy in the US specifically indicated for the treatment of this condition. TSC is a rare genetic disorder affecting up to one million people worldwide. Approximately 85% of individuals with TSC are affected by epilepsy, and uncontrolled seizures associated with TSC can be debilitating for patients. More than 60% of TSC patients who experience seizures stop responding to available anti-epileptic therapies. 

EXIST-3 is the first Phase III study to demonstrate the significant benefit of adjunctive Afinitor DISPERZ in the treatment of patients with TSC-associated partial-onset seizures. Afinitor® is the only approved non-surgical option indicated for treating TSC-associated non-cancerous brain tumors (subependymal giant cell astrocytoma, or SEGA) and TSC-associated kidney tumors (renal angiomyolipoma).

“We are pleased that this latest approval for Afinitor DISPERZ in the US will make an important difference to patients with tuberous sclerosis complex who experience partial-onset seizures, one of the most debilitating manifestations of TSC,” said Ameet Mallik, executive vice president, Novartis Oncology US. “This is a welcome advance that reinforces the commitment of Novartis to patients with rare diseases.”

The FDA approval of Afinitor DISPERZ was based on efficacy and safety data from a pivotal Phase III study, EXIST-3 (EXamining everolimus In a Study of TSC), which found that when used as an adjunctive therapy, Afinitor DISPERZ significantly reduced the frequency of treatment-resistant seizures associated with TSC compared to placebo. 

Afinitor works by inhibiting the mammalian target of rapamycin (mTOR), a protein that regulates multiple cellular functions. In TSC, inactivating mutations in either the TSC1 or the TSC2 gene lead to hamartoma formation throughout the body as well as seizures and epileptogenesis. Overactivation of mTOR results in neuronal dysplasia, aberrant axonogenesis and dendrite formation, increased excitatory synaptic currents, reduced myelination, and disruption of the cortical laminar structure causing abnormalities in neuronal development and function.