Positive results from the randomized phase 2 ELEKTRA study of Soticlestat in children with Dravet syndrome ( DS ) or Lennox-Gastaut syndrome ( LGS ) were announced.
Soticlestat is a potent, highly selective, oral, first-in-class inhibitor of the enzyme cholesterol 24-hydroxylase ( CH24H ).
It is being investigated for the treatment of rare developmental and epileptic encephalopathies ( DEEs ), a group of highly refractory epilepsy syndromes including Dravet syndrome and Lennox-Gastaut syndrome.
The ELEKTRA study achieved its primary endpoint with high statistical significance, demonstrating a 27.8% median reduction from baseline in convulsive seizure ( DS ) and drop seizure ( LGS ) frequency compared to a 3.1% median increase in patients taking placebo during the 12-week maintenance period ( median placebo-adjusted reduction=30.5%; p=0.0007, based on the efficacy analysis set of 120 patients with seizure data in the maintenance period ).
In addition, DS and LGS patients treated with Soticlestat have demonstrated a 29.8% median reduction in convulsive seizure ( DS ) and drop seizure ( LGS ) frequency compared to 0.0% change in median seizure frequency in patients taking placebo during the full 20-week treatment period ( titration plus maintenance ) of the ELEKTRA study ( placebo-adjusted reduction=25.1%; p=0.0024 ).
In the ELEKTRA DS cohort ( n=51 ), patients treated with Soticlestat have demonstrated a 33.8% median reduction in convulsive seizure frequency compared to a 7.0% median increase in patients taking placebo during the full 20-week treatment period of the study ( median placebo-adjusted reduction in seizure frequency is 46.0%; p=0.0007 ).
In the ELEKTRA LGS cohort ( n=88 ), patients treated with Soticlestat have demonstrated a 20.6% median reduction in drop seizure frequency compared to a 6.0.% median reduction in patients taking placebo during the full 20-week treatment period of the study ( median placebo-adjusted reduction in seizure frequency is 14.8%; p=0.1279 ).
Soticlestat was generally well-tolerated in the ELEKTRA study and has demonstrated a safety profile consistent with those of previous studies, with no new safety signals identified.
All patients who completed the ELEKTRA study elected to enroll into the ENDYMION open-label extension study.
Dravet syndrome and Lennox-Gastaut syndrome are types of developmental and epileptic encephalopathies, a heterogeneous group of rare epilepsy syndromes.
Dravet and Lennox-Gastaut syndrome typically become apparent during infancy or early childhood and are highly refractory to many antiseizure medications.
Dravet syndrome is most commonly caused by a genetic mutation in the SCN1A gene and affects approximately 1 in 15,000 to 1 in 21,000 people in the United States.
Dravet syndrome is characterized by prolonged focal seizures that can evolve to convulsive tonic-clonic seizures.
Children with Dravet syndrome experience developmental disabilities as seizures increase. Other common symptoms include changes in appetite, difficulty balancing and a crouched gait when walking.
Lennox-Gastaut syndrome is estimated to affect approximately 1 in 11,000 people in the United States.
Lennox-Gastaut syndrome is a heterogeneous condition and characterized by several different types of seizures, most commonly atonic ( drop ), tonic and atypical absence seizures.
Children with Lennox-Gastaut syndrome may also develop cognitive dysfunction, delays in reaching developmental milestones and behavioral problems.
Lennox-Gastaut syndrome can be caused by a variety of underlying conditions, but in some cases no cause can be identified. ( Xagena )
Source: Ovid Therapeutics & Takeda Pharmaceutical, 2020