Data from a randomized phase 2 ELEKTRA study (NCT03650452) (Takeda Pharmaceutical, New York, NY) showed soticlestat treatment reduced seizure frequency in children with Dravet syndrome (DS) or Lennox-Gastaut syndrome (LGS). Soticlestat is a potent, highly selective, oral, first-in-class inhibitor of the enzyme cholesterol 24-hydroxylase (CH24H). Soticlestat is being investigated for the treatment of rare developmental and epileptic encephalopathies (DEEs), a group of highly refractory epilepsy syndromes including DS and LGS.
There was a 27.8% median reduction from baseline in convulsive seizure (DS) and drop seizure (LGS) frequency compared with a 3.1% median increase in participants who took placebo during a 12-week maintenance period (median placebo-adjusted reduction=30.5%; P=0.0007, based on the efficacy analysis of 120 participants for whom there are seizure data in the maintenance period). In addition, participants with DS and LGS who were treated with soticlestat had a 29.8% median reduction in convulsive seizure (DS) and drop seizure (LGS) frequency compared to 0.0% change in median seizure frequency in those treated with placebo during the full 20-week treatment period (titration plus maintenance) (placebo-adjusted reduction=25.1%; P=.0024).
In the Elektra LGS cohort (n=88), participants treated with soticlestat for 20 weeks had a median 20.6% reduction in drop seizure frequency compared with a median 6.0.% reduction in participants treated with placebo for the 20-week treatment period (median placebo-adjusted seizure-frequency reduction 14.8%; P=.1279). Additional analyses are being conducted to better understand the potential next steps for the development of soticlestat in this highly heterogenous patient population.
In the Elektra DS cohort (n=51), participants treated with soticlestat had a median 33.8% reduction in convulsive seizure frequency compared with a median 7.0% increase in participants treated with placebo over the 20-week treatment period (median placebo-adjusted reduction in seizure frequency 46.0%; P=.0007). A phase 3 registrational program for soticlestat in patients with DS is being considered.
Soticlestat was generally well-tolerated in the Elektra study and demonstrated a safety profile consistent with previous studies, with no new safety signals identified. All participants who completed the Elektra study elected to enroll into the Endymion open-label extension study.
Jill M. Giordano Farmer, DO
Nidhiben Anadani, MD
Jakai D. Nolan, DO, MPH, and Jacqueline A. Nicholas, MD, MPH