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).

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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.