Abstract Details

Title Extended Duration Safety and Efficacy of Adjunctive Ganaxolone Treatment in Patients with CDKL5 Deficiency Disorder: 8-Month Minimum Open-Label Extension Follow-up

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) S13 - Epilepsy/Clinical Neurophysiology (EEG): Antiseizure Medications (1:48 PM-2:00 PM)

Poster/Presentation
Number 005

Background Cyclin-dependent kinase-like 5 deficiency disorder (CDD) is a developmental epileptic encephalopathy with highly drug-resistant seizures. In a recent placebo-controlled phase 3 study, ganaxolone (GNX) significantly reduced major motor seizure frequency (MMSF) over the 17-week treatment period (ganaxolone 30.7% vs placebo 6.9%; p=0.0036) in patients with CDD.

Objective To report an 8-month minimum follow-up analysis of the open-label extension (OLE) study of ganaxolone in the treatment of CDD (cut-off 24Feb2021).

Design/Methods Patients with CDD (aged 2-21 years) who completed the 17-week double-blind phase were eligible to enroll in the OLE. Reductions in MMSF (bilateral motor, >3 seconds) from pre-randomization baseline to 2-month intervals in the OLE, safety and tolerability were assessed.

Results

Of 101 patients entering the double-blind phase, 88 (87.1%) continued into the OLE (43 were initially randomized to ganaxolone (GNX-GNX) and 45 to placebo (PBO-GNX)). At the time of entry into the double-blind study, median age of patients was 5 years; 79.5% were female with median monthly MMSF of 50.6. Median treatment time in the OLE was 262 days. At the time of this analysis, 31 (35.2%) patients withdrew from the OLE, with lack of efficacy (38.7%; n=12) and adverse events (29.0%; n=9) being the most common reasons for discontinuation. Median MMSF reduction from baseline in the OLE was 30.1% in the GNX-GNX arm (n=38) and 33.3% in the PBO-GNX arm (n=34) at 8 months and 46.5 (n=22) and 53.8 (n=26), respectively, at 12 months. Ganaxolone was generally well-tolerated and no new safety findings emerged.

Conclusions Safety findings from this OLE analysis are consistent with the safety in the double-blind phase as well as the known safety profile of ganaxolone. Data from the OLE provides supportive evidence for maintenance of effect in reducing major motor seizures associated with CDD at approximately 8 months and up to 12 months in patients who continue treatment.

Authors/Disclosures
Ian Miller, MD PRESENTER	Dr. Miller has received personal compensation for serving as an employee of Marinus Pharmaceuticals. Dr. Miller has stock in Marinus Pharmaceuticals.
Heather E. Olson, MD (Boston Children's Hospital Peabody)	Dr. Olson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda pharmaceuticals. The institution of Dr. Olson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ovid Therapeutics. The institution of Dr. Olson has received research support from NINDS. The institution of Dr. Olson has received research support from International Foundation for CDKL5 Research. The institution of Dr. Olson has received research support from Marinus Pharmaceuticals. The institution of Dr. Olson has received research support from Ovid Therapeutics.
Ahsan M. Naduvil Valappil, MD (Cleveland Clinic)	Dr. Naduvil Valappil has nothing to disclose.
Eva Rybak, PharmD (Marinus)	Dr. Rybak has received personal compensation for serving as an employee of Marinus Pharmaceuticals . Dr. Rybak has received stock or an ownership interest from Marinus Pharmaceuticals .
Alex Aimetti (Marinus Pharmaceuticals)	No disclosure on file
Joseph Hulihan, Jr., MD (Marinus Pharmaceuticals)	Dr. Hulihan has received personal compensation for serving as an employee of MARINUS PHARMACEUTICALS. Dr. Hulihan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for ZYNERBA PHARMACEUTICALS.
Elia M. Pestana Knight, MD (Cleveland Clinic)	Dr. Pestana Knight has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Marinus Pharmaceuticals. Dr. Pestana Knight has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Marinus Pharmaceuticals.