Everolimus Effective in Reducing Seizures in Tuberous Sclerosis Complex

The drug, which is indicated to treat certain types of cancer, is effective at reducing seizures in TSC when used as adjunctive therapy.

VANCOUVER, British Columbia – When used as adjunctive therapy, everolimus significantly reduces pharmacoresistant seizures in patients with tuberous sclerosis complex (TSC) compared to placebo.

Researchers reported the data from the Examining  in a Study of TSC (EXIST-3) trial at the 2016 annual meeting of the American Academy of Neurology (AAN).

Patients with TSC often experience seizures; however, up to two-thirds of patients are unable to achieve seizure control with currently available antiepileptic drugs (AEDs).

In this study, 366 patients (aged 2.2-56.3 years) with TSC and pharmacoresistant seizures were randomly assigned to either low exposure (3 to 7 ng/mL; n=117) of everolimus, high exposure (9 to 15 ng/mL; n=130), or placebo (n=119). Patients in all 3 treatment arms were also taking up to 3 AEDs.

From baseline, the percentage reduction in seizure frequency among low-exposure everolimus patients was 29.3% (P=.003) and 39.6% for high-exposure everolimus patients (P<.001) compared with 14.9% in the placebo group. More than 28% and 40% of patients in the low- and high-exposure groups (P=.008; P<.001), respectively, experienced a greater than 50% reduction in seizures compared with 15.1% of patients in the placebo group.

“These findings are encouraging as this is the first clinical study demonstrating benefit specifically for TSC patients who suffer from treatment-resistant seizures,” lead investigator Jacqueline French, MD, assistant professor and Director of Translational Research and Clinical Trials in Epilepsy at NYU Langone Medical Center, said in a statement.

The most common adverse events reported in the treatment groups vs placebo were stomatitis (28.2%, 30.8% vs 3.4%), mouth ulceration (23.9%, 21.5% vs 4.2%), diarrhea (17.1%, 21.5% vs 5%), nasopharyngitis (13.7%, 16.2% vs 16%), upper respiratory tract infection (12.8%, 15.4% vs 12.6%), aphthous ulcer (4.3%, 14.6% vs 1.7%), pyrexia (19.7%, 13.8% vs 5%), vomiting (12%, 10% vs 9.2%), cough (11.1%, 10% vs 3.4%), and rash (6%, 10% vs 2.5%) Serious adverse events were reported in 13.7% and 13.8% of patients in the treatment groups compared to 2.5% in the placebo group.

Click here for more coverage from the 68th Annual Meeting of the American Academy of Neurology, April 15-21, 2016, in Vancouver, British Columbia, Canada.


French J, et al. Adjunctive everolimus therapy for the treatment of refractory seizures associated with tuberous sclerosis complex: results from a randomized, placebo-controlled, phase 3 trial. Presented at: The 68th Annual Meeting of the American Academy of Neurology; April 15-21, 2016; Vancouver, British Columbia.