FDA Approves First Adjunctive Treatment for TSC-Associated Seizures

This morning, it was announced that everolimus (Afinitor DISPERZ) has become the first therapy to be specifically approved by the U.S. Food and Drug Administration (FDA) to treat patients aged 2 years and older with tuberous sclerosis complex (TSC)-associated partial-onset seizures.

The drug, developed by Novartis, was first given the go-ahead in May 2011 for the treatment of progressive neuroendocrine tumors of pancreatic origin (PNET) in patients with unresectable, locally advanced or metastatic disease. It had also been previously approved by the FDA for the treatment of adult and pediatric patients aged 1 year and older with TSC who have subependymal giant cell astrocytoma (SEGA) and adults with angiomyolipomas.

The new indication will address a completely unmet need, as more than 60% of patients with TSC suffer from seizures that have become resistant to available anti-epileptic medicines.

"In TSC, 85 percent of individuals have seizures at some point in their lifetime. But very importantly and urgently, more than 60% experience intractable epilepsy, and this new indication for Afinitor means they now have a much-needed new treatment option," said TS Alliance President & CEO Kari Luther Rosbeck in a press release. "Afinitor is the first mTOR inhibitor approved in the United States for the treatment of epilepsy and further demonstrates TSC as a model system for developing new therapies."

Everolimus has been designed to inhibit the mammalian target of a protein that regulates multiple cellular functions, known as rapamycin (mTOR). Pre-clinical research had suggested that hyperactive mTOR activity has the potential to influence several mechanisms of epileptogenesis, the progressive process by which the brain develops epilepsy.

The approval is primarily based off the success of the EXIST-3 Phase 3 clinical trial of everolimus. Results from the study showed the drug to achieve clinically significant seizure control in TSC patients compared to placebo. In the study, 366 patients with TSC and treatment-resistant seizures were randomized to receive targeted concentrations of everolimus titrated to Low Exposure (LE), High Exposure (HE) or placebo. The percentage reduction from baseline in seizure frequency was significantly greater among patients randomized to everolimus LE and HE vs placebo. Seizure response rate was also significantly greater with everolimus LE and HE vs placebo.

"The TS Alliance certainly appreciates the FDA's attention to the needs of the TSC community," said Rosbeck. "We are also grateful to Novartis along with the study's clinicians and researchers as well as those who volunteered to take part in the clinical trial."

"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.

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