What side effects are associated with this type of intervention?

Common treatments for Lennox-Gastaut Syndrome (LGS) include antiepileptic drugs such as valproate, lamotrigine, topiramate, and cannabidiol. Known side effects of these treatments can include dizziness, fatigue, gastrointestinal issues, weight changes, and potential liver toxicity. For treatments similar to Soticlestat, such as other cholesterol 24-hydroxylase inhibitors, specific side effects are not well-documented, but they may share similar profiles with other antiepileptic drugs, including potential impacts on liver function and metabolic processes.

What prior FDA approvals exist?

Several drugs have been approved by the FDA for the treatment of Lennox-Gastaut Syndrome (LGS). These include cannabidiol (Epidiolex), which has shown efficacy in reducing seizure frequency in patients with LGS. Other approved treatments include clobazam (Onfi), rufinamide (Banzel), and lamotrigine (Lamictal). While soticlestat, a cholesterol 24-hydroxylase inhibitor, is still under investigation, these existing treatments provide a range of options for managing LGS.

What other types of research exist?

Promising novel alternatives to Soticlestat for Lennox-Gastaut Syndrome patients include: 1) Fenfluramine (Fintepla), which has been approved by the FDA for LGS and has shown significant seizure reduction. 2) Cannabidiol (Epidiolex), which is also FDA-approved for LGS and has demonstrated efficacy in reducing seizure frequency. 3) Stiripentol, which has been used effectively in combination with other AEDs for LGS. These alternatives have shown promising results in clinical trials and are viable options for treatment in 2024.

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Soticlestat for Dravet Syndrome

Q: What is the mechanism of action of this treatment?

Lennox-Gastaut Syndrome (LGS) is a severe form of epilepsy that requires treatments targeting multiple pathways to control seizures. Soticlestat, a cholesterol 24-hydroxylase inhibitor, works by reducing neurosteroid synthesis, which can modulate neuronal excitability and seizure activity. Other common treatments include valproate, which increases GABA levels to inhibit neuronal firing, and clobazam, a benzodiazepine that enhances GABAergic transmission. These mechanisms are crucial for LGS patients as they help reduce the frequency and severity of seizures, improving quality of life and reducing the risk of developmental delays and other complications associated with uncontrolled seizures.

Phase 3

Recruiting

Research Sponsored by Takeda

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be younger than 65 years old

Must not have

Participant is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property. Participants who have positive answers on item numbers 4 or 5 on the CSSRS before dosing are excluded. This scale will only be administered to participants aged ≥6 years.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 4 years

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial tests soticlestat to reduce seizures in children and adults with Dravet Syndrome or Lennox-Gastaut Syndrome. Soticlestat helps by targeting brain pathways involved in seizure activity. The study will evaluate its safety, effectiveness, and tolerance over time.

Who is the study for?

This trial is for children and adults with Dravet Syndrome or Lennox-Gastaut Syndrome who were in a phase 3 soticlestat study. They must not have significant heart rhythm issues, be at risk of suicide, or have other serious health problems that could affect the study.

What is being tested?

The trial tests if adding soticlestat to standard seizure treatments helps reduce seizures in patients with Dravet or Lennox-Gastaut Syndromes. Participants will take soticlestat tablets alongside their usual medication and attend regular visits.

What are the potential side effects?

While specific side effects are not listed here, participants may experience adverse reactions related to soticlestat on top of their current anti-seizure medications. These will be monitored throughout the study.

Eligibility Criteria

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I am not at risk of harming myself or others.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 4 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Absolute Value for Tanner Stage for Children 6 to 17 Years of Age During the Study

Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Score

Number of Participants With At Least One Treatment Emergent Adverse Event (TEAE)

Secondary study objectives

CGI-I Nonseizure Symptoms Score

CGI-I Seizure Intensity and Duration Score

Caregiver Global Impression of Improvement (Care GI-I) Score

+5 more

Side effects data

From 2024 Phase 3 trial • 270 Patients • NCT04938427

14%

Somnolence

13%

Change in seizure presentation

Upper respiratory tract infection

Nasopharyngitis

Pyrexia

Decreased appetite

Fatigue

COVID-19

Constipation

Fall

Diarrhoea

Vomiting

Oxygen saturation decreased

Influenza

Cataract

Pneumonia

Urinary tract infection

Status epilepticus

Pyelonephritis

COVID-19 pneumonia

Acute respiratory failure

Rhinovirus infection

100%

80%

60%

40%

20%

Study treatment Arm

Soticlestat

Placebo

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: SoticlestatExperimental Treatment1 Intervention

Participants with DS and LGS will receive:Participants weighing \<45kg:Soticlestat,mini-tablets,titrated from lower dose level(60mg to 140mg) to higher dose(100mg to 200mg) twice daily(BID),based on body weight,orally/via enteral feeding tubes including but not limited to nasogastric(NG)-tube,gastrostomy tube(G-tube),MIC-KEY button,upto 2 weeks in Titration Period. Will continue to receive dose they are on at end of Titration Period,for approximately 4 years in Maintenance Period.Dose will be tapered down to lower dose(not less than lowest dose level based on weight)every 3 days until study drug is discontinued(upto 1week) in Taper Period.Participants weighing ≥45kg/adults:Soticlestat mini-tablets/tablets with starting dose of 200mg BID followed by 300mg BID,up to 2 weeks in Titration Period.Will continue to receive 300mg BID for approximately 4 years in Maintenance Period.Dose will be tapered down upto 100mg every 3 days until study drug is discontinued(up to 1 week) in Taper Period.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Soticlestat

2022

Completed Phase 3

~640

0 / 1Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Lennox-Gastaut Syndrome (LGS) is a severe form of epilepsy that requires treatments targeting multiple pathways to control seizures. Soticlestat, a cholesterol 24-hydroxylase inhibitor, works by reducing neurosteroid synthesis, which can modulate neuronal excitability and seizure activity. Other common treatments include valproate, which increases GABA levels to inhibit neuronal firing, and clobazam, a benzodiazepine that enhances GABAergic transmission. These mechanisms are crucial for LGS patients as they help reduce the frequency and severity of seizures, improving quality of life and reducing the risk of developmental delays and other complications associated with uncontrolled seizures.