Effect of fenfluramine on convulsive seizures in CDKL5 deficiency disorder
Orrin Devinsky, LaToya King, Danielle Schwartz, Erin Conway, Dana Price, Orrin Devinsky, LaToya King, Danielle Schwartz, Erin Conway, Dana Price
Abstract
CDKL5 deficiency disorder (CDD) is an X-linked pharmacoresistant neurogenetic disorder characterized by global developmental delays and uncontrolled seizures. Fenfluramine (FFA), an antiseizure medication (ASM) indicated for treating convulsive seizures in Dravet syndrome, was assessed in six patients (five female; 83%) with CDD whose seizures had failed 5-12 ASMs or therapies. Median age at enrollment was 6.5 years (range: 2-26 years). Mean FFA treatment duration was 5.3 months (range: 2-9 months) at 0.4 mg/kg/day (n = 2) or 0.7 mg/kg/day (n = 4; maximum: 26 mg/day). One patient had valproate added for myoclonic seizures. The ASM regimens of all other patients were stable. Among five patients with tonic-clonic seizures, FFA treatment resulted in a median 90% reduction in frequency (range: 86%-100%). Tonic seizure frequency was reduced by 50%-60% in two patients with this seizure type. One patient experienced fewer myoclonic seizures; one patient first developed myoclonic seizures on FFA, which were controlled with valproate. Adverse events were reported in two patients. The patient with added valproate experienced lethargy; one patient had decreased appetite and flatus. No patient developed valvular heart disease or pulmonary arterial hypertension. Our preliminary results suggest that FFA may be a promising ASM for CDD. Randomized clinical trials are warranted.
Trial registration: ClinicalTrials.gov NCT03861871.
Keywords: CDKL5 deficiency disorder; epilepsy; fenfluramine.
Conflict of interest statement
OD: Research funding, Novartis, PTC Therapeutics, Zogenix; Equity interest, Rettco, Pairnomix, Tilray, and Egg Rock Holdings; LK, DP: No disclosures. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
© 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
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Source: PubMed