Fenfluramine to treat convulsive seizures in patients with CDKL5 deficiency disorder
Abstract number :
1060
Submission category :
4. Clinical Epilepsy / 4C. Clinical Treatments
Year :
2020
Submission ID :
2423393
Source :
www.aesnet.org
Presentation date :
12/7/2020 1:26:24 PM
Published date :
Nov 21, 2020, 02:24 AM
Authors :
Orrin Devinsky, New York University Langone Medical Center; LaToya King - New York University Langone Medical Center; Dana Price - New York University Langone Medical Center;;
Rationale:
CDKL5 Deficiency Disorder (CDD) is an X-linked neurogenetic disorder resulting from mutations in the CDKL5 gene that codes for a kinase involved in neurodevelopment, including synaptic plasticity and glutamatergic signaling. It has an incidence of 1/40,000 live births and presents in the first 3 months of life. Primary symptoms are severe epilepsy and global developmental delays. Most children have uncontrolled seizures despite available therapies; thus there is a desperate need for more effective antiseizure therapies. Fenfluramine (FFA) is a drug which increases serotonergic activity primarily by releasing neuronal serotonin and is a positive modulator of sigma-1 receptors. FFA is effective in treating convulsive seizures in patients with Dravet syndrome and has been approved by the FDA for this indication.
Method:
We assessed the efficacy of FFA in 6 children with CDD with uncontrolled epilepsy whose seizures failed to be controlled with 5 to 12 antiseizure medications as well as with dietary and other therapies.
Results:
The 6 patients included 5 girls and 1 boy. Median age at enrollment was 6.5 years (range 4 to 26 years). They were treated with FFA for 2-9 months (mean 5.3 months). 4 patients received the maximum dose of 0.7 mg/kg/day (absolute maximum of 26 mg/day); 2 patients were maintained on 0.4 mg/kg/day. Among the 5 patients with tonic-clonic seizures, FFA treatment was associated with a median 90% reduction (range 86% to 100%; Figure). Among 2 patients with tonic seizures, there was a 50-60% reduction in their frequency. One patient had a reduction in myoclonic seizures and 1 patient first developed myoclonic seizures on FFA. Two patients reported adverse events: lethargy when valproate was started (the only patient who had a new medication added on FFA therapy; VPA led to a reduction in myoclonic seizures) and 1 had decreased appetite and flatus. No patient developed valvular heart disease or pulmonary arterial hypertension.
Conclusion:
FFA is a promising antiseizure medication for patients with CDD. Our preliminary results suggest FFA is effective in controlling tonic-clonic seizures. Randomized controlled trials should be undertaken.
Funding:
:Zogenix, Inc.
Clinical Epilepsy