This year, the American Academy of Neurology (AAN) Annual Meeting took place virtually from April 17-22, 2021. During the meeting, a variety of stakeholders discussed new treatments and research within the field of neurology. According to Neurology Advisor, one presentation focused on the efficacy, tolerability, and safety of soticlestat for pediatric patients with either Dravet syndrome or Lennox-Gastaut syndrome (LGS). Interested in seeing the full abstract? Search here for abstract #S1.005.

Soticlestat

According to a prior press release from Takeda Pharmaceutical Company Ltd. (“Takeda”), soticlestat is:

a potent, highly selective, first-in-class inhibitor of the enzyme cholesterol 24-hydroxylase (CH24H), with the potential to reduce seizure susceptibility and improve seizure control. CH24H is predominantly expressed in the brain, where it converts cholesterol into 24S-hydroxycholesterol (24HC) to adjust the homeostatic balance of brain cholesterol [and] recent literature indicates that…increased expression of CH24H can…[result] in neurotoxicity.

Takeda secured developmental and commercialization rights to soticlestat through an exclusive partnership with Ovid Therapeutics Inc. (“Ovid”).

Within this study, researchers evaluated the safety, efficacy, and tolerability of soticlestat for pediatric patients with Dravet syndrome or LGS. Altogether, 51 patients with Dravet syndrome enrolled. 88 children with LGS enrolled. All patients within the  Phase 2 ELEKTRA clinical trial were between ages 2-17. During the trial, patients received a weight-adjusted dose of soticlestat up to 600mg – or a placebo – for a 20-week period. The goal was to determine whether the therapy improved baseline seizure frequency. For the purposes of this trial, seizure frequency was 3+ convulsive seizures per month for Dravet syndrome or 4+ drop seizures per month for LGS. Overall, researchers discovered:

• In patients with Dravet syndrome, the median placebo-adjusted seizure frequency fell by 46%. Alternately, in patients with LGS, seizure reduction fell by 14.8%. Altogether, considering all of the data, soticelestat reduced seizure frequency by 25.1%.
  • This is particularly important as Dravet syndrome is normally difficult to treat due to treatment-averse epilepsy. Thus, soticlestat could fulfill an unmet patient need.
• Approximately 80.3% of patients taking soticlestat experienced side effects or adverse reactions. Most commonly reported symptoms included constipation and lethargy.
• Altogether, 15.5% of patients treated experienced severe adverse reactions. However, researchers still believe that soticlestat is relatively safe for pediatric patients.

Dravet Syndrome

Although Charlotte Dravet first described Dravet syndrome around 43 years ago, the condition’s genetic basis was not found until 2001. Typically, SCN1A gene mutations cause this rare epilepsy. However, other genetic mutations such as HCN1 may also lead to a Dravet syndrome diagnosis. Normally, this epilepsy appears within the first year of life in an otherwise healthy infant. However, the epilepsy will last a lifetime. Dravet syndrome affects males and females equally. If your child is experiencing any of the following, please consider speaking to your doctor about a Dravet syndrome diagnosis:

• Seizures which last for 10+ minutes
• Epileptic seizures affecting one side of the body
• Any seizures triggered by warm water in children under 1 year old

As Dravet syndrome progresses, patients may experience prolonged febrile and non-febrile seizures; myoclonic or partial seizures; or ataxia. Within the first few years of life, patients may experience status epilepticus (SE), a serious and continuous seizure requiring medical care. Other symptoms include:

• Unsteady or uncoordinated gait
• Cognitive or developmental delays
• Impaired speech
• Loss of coordination
• Behavioral disorders
• Decreased muscle tone

Learn more about Dravet syndrome here.

Lennox-Gastaut Syndrome (LGS)

An estimated 5% of childhood epilepsy diagnoses relate to Lennox-Gastaut syndrome (LGS), a rare and severe epilepsy appearing in childhood. Typically, symptoms and seizures appear between ages 2-6. Patients with LGS often have frequent and diverse seizures. However, doctors are not sure exactly what causes LGS. Potential causes include premature birth and a low birth weight; a lack of oxygen at birth; severe brain injury or brain development problems; encephalitis or meningitis; or a variety of genetic disorders.

Patients with LGS may experience atonic seizures (sudden loss of muscle tone, causing someone to collapse); tonic seizures (muscle stiffening which often occurs while sleeping); or absence seizures (prolonged episode of epileptic activity). Thus, frequent and severe seizures are often the clearest symptom of LGS. However, patients may display other symptoms, including:

• Cognitive and developmental delays
• Injuries associated with falling
• Muscle stiffness, rigidity, or jerking
• Difficulty processing information
• Behavioral problems which could develop into psychosis
• Drooping eyelids
• Head nodding or rapid blinking
• Loss of awareness
• Partial or complete loss of consciousness