Authors :
Presenting Author: John Flatt, MD – Marinus Pharmaceuticals, Inc.
Alex Aimetti, PhD – Marinus Pharmaceuticals, Inc.; Ian Miller, MD – Marinus Pharmaceuticals, Inc.
Rationale:
Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a developmental and epileptic encephalopathy characterized by global developmental impairment and early-onset, refractory seizures. Ganaxolone, a neuroactive steroid and positive allosteric modulator that targets both synaptic and extrasynaptic GABAA receptors, is FDA-approved for the treatment of seizures associated with CDD in patients 2 years of age and older. Here we review the clinical data obtained from ganaxolone patient enrollment forms, submitted to a specialty pharmacy for patients with CDD, to assess the clinical features of patients being prescribed ganaxolone.
Methods:
A retrospective analysis was conducted using de-identified patient enrollment form clinical data from a single specialty pharmacy in the United States. Patients included in the analysis had CDD (ICD-10 G40.42) and were prescribed ganaxolone between July 2022 and February 2023. Collected clinical data included epilepsy-related ICD-10 codes, age at seizure onset, previously and concomitantly utilized medications, additional seizure interventions, and current seizure burden. A subgroup analysis based on demographic factors was not performed.Results:
Data from 114 patients were included in the analysis. At the time of prescribing, 54.4% of patients were experiencing daily seizures (>30 seizures/month) with another 28.9% experiencing weekly seizures (four to twenty-nine seizures/month). Seizure onset, when known, occurred within the first three months of life in 72.5% of patients. The three most frequent seizure-related ICD-10 diagnoses beyond CDD were “Lennox-Gastaut Syndrome,” followed by “epilepsy, unspecified,” and “other generalized epilepsy and epileptic syndromes.” The most common medications discontinued prior to ganaxolone prescription were levetiracetam, topiramate, phenobarbital, and valproate. The most common concomitant medications were clobazam, levetiracetam, cannabidiol, and valproate. In this group of patients, additional active or previously used non-pharmacological interventions included 31 patients on the ketogenic diet and 25 patients with a vagal nerve stimulator.Conclusions:
This real-world clinical prescribing data provides valuable insights into the population of CDD patients that healthcare providers are intending for ganaxolone use as the next line of antiseizure therapy. Early prescription data suggests use across the spectrum of seizure burden including many patients with highly refractory epilepsy. These results represent the first step in establishing evidence surrounding the real-world use of ganaxolone to help further inform clinical decision-making for providers treating patients with CDD.Funding:
Marinus Pharmaceuticals, Inc.