Everolimus Safe, Effective for Reduction of Seizures in Tuberous Sclerosis Complex

The EXIST-3 trial is the first phase 3 study to evaluate the use of EVE for the adjunctive treatment of seizures in TSC.

VANCOUVER – Adjunctive treatment with everolimus (EVE) helps to reduce seizure frequency in patients with tuberous sclerosis complex.

The results from the EXIST-3 trial were reported at the 2016 Child Neurology Society Annual Meeting in Vancouver, British Columbia, October 26-29, 2016.

The randomized, placebo-controlled, double-blind phase 3 study evaluated the safety and efficacy of EVE 3-7 ng/mL (low trough [LT]) or 9-15 ng/mL (high trough [HT]) targeted trough concentration (Cmin) vs placebo as adjunctive treatment in patients aged 2 to 65 years with refractory seizures linked to tuberous sclerosis complex.

After an 8-week baseline period, patients were randomly assigned to EVE LT (n=117), EVE HT (n=130), or placebo (n=119), with dose titrations made throughout as needed. The primary end points included average weekly reduction in seizure frequency from baseline, which was expressed as a response rate (RR ≥50%), and percentage reduction.

Compared with placebo (14.9%), the median percentage reduction in seizure frequency was statistically significant for EVE LT (29.3%, P = .003) and EVE HT (39.6%, P <.001). The response rate was also statistically significant, with an RR of 28.3% for patients receiving EVE LT (P =.008) and 40% in patients receiving EVE HT (P <.001) compared with placebo (15.1%).

Adverse events reported in ≥20% of patients receiving LT, HT, or placebo included stomatitis (28.2%, 30.8%, 3.4%), diarrhea (17.1%, 21.5%, 5%), and mouth ulceration (23.9%, 21.5%, 4.2%). Discontinuation as a result of adverse events was 4.3%, 3.1%, and 1.7% among patients who received EVE LT, HT, or placebo, respectively.

Overall, treatment with EVE appears to be safe and produces significant reductions in seizure frequency in patients with tuberous sclerosis complex.

For more coverage of CNS 2016, go here.


Franz D, Lawson J, Nabbout R, 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: 2016 Child Neurology Society Annual Meeting. October 26-29, 2016; Vancouver, BC. Abstract 41.  

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