Ganaxolone for use in treating tuberous sclerosis complex and seizure disorders
Inventors
HULIHAN, Joseph • Aimetti, Alex • BRAUNSTEIN, Scott
Assignees
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Publication Number
US-12268696-B2
Publication Date
2025-04-08
Expiration Date
Abstract
The disclosure to methods for treating tuberous sclerosis complex and epilepsy disorders comprising administering to a subject in need thereof a therapeutically effective amount of ganaxolone or a pharmaceutically acceptable salt thereof.
Core Innovation
The document describes using ganaxolone to treat seizures associated with tuberous sclerosis complex (TSC) and related seizure disorders. A central aspect is a two-phase titration approach designed to mitigate an unexpected interaction with concomitant cannabidiol (CBD). In the described context, CBD exposure is associated with changes in tolerability and seizure suppression outcomes in an open-label TSC trial.
The background-to-results narrative reports that patients receiving CBD above a threshold described as above about 10 mg/kg/day show lower seizure suppression and increased somnolence and tolerability issues. The document further reports that these somnolence-associated tolerability effects correlate with higher ganaxolone plasma concentrations. The proposed approach aims to reach therapeutic ganaxolone plasma concentrations while reducing somnolence-associated efficacy loss.
The document proposes dose escalation in two phases to reach therapeutic ganaxolone plasma levels described as about 75–175 ng/mL by about 4–5 weeks while managing tolerability. It describes dosing schedules that include fixed mg/day escalation and weight-based mg/kg/day escalation regimens, with titration stopping at a specified upper dose for higher-dose CBD patients and optional continuation for some patients. It also states inclusion of formulations such as oral liquid or oral suspension and provides additional trial-linked analysis in a CDKL5 deficiency disorder context connecting somnolence-related adverse events to reduced efficacy.
Claims Coverage
The partial content provides two independent claims, each directed to oral ganaxolone administration with a stepwise, escalating dosing regimen for treating seizures associated with CDKL5 deficiency disorder. Both independent claims focus on the titration pattern over successive treatment periods followed by a remaining treatment period.
Stepwise oral ganaxolone escalation for CDKL5 deficiency disorder
Orally administering ganaxolone in an amount of about 150 mg per day for about one week, followed by about 300 mg per day for about one week, followed by about 600 mg per day for about one week, followed by about 1,200 mg per day for about one week, followed by about up to 1,800 mg per day for the remaining treatment period.
Weight-based stepwise oral ganaxolone escalation for CDKL5 deficiency disorder
Orally administering ganaxolone in an amount of about 6 mg/kg/day for about one week, followed by about 12 mg/kg/day for about one week, followed by about 24 mg/kg/day for about one week, followed by about 42 mg/kg/day for about one week, followed by about up to 63 mg/kg/day for the remaining treatment period.
Across the two independent claims, the core claim coverage is directed to oral ganaxolone treatment of seizures associated with CDKL5 deficiency disorder using an escalation regimen with successive about-one-week dose steps and a specified remaining treatment period, using either fixed daily mg amounts or weight-based mg/kg/day amounts.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating seizures associated with tuberous sclerosis complex (TSC) using ganaxolone with a two-phase titration approach in the presence of concomitant cannabidiol (CBD).
A phase 2 open-label TSC trial finding is reported, including somnolence-related tolerability and seizure suppression outcomes associated with CBD exposure and ganaxolone plasma concentrations.
A phase 3 randomized placebo-controlled trial design in TSC is described.
Additional supporting analysis from a CDKL5 deficiency disorder (CDD) phase 3 study is described, linking somnolence-related adverse events to reduced efficacy.
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