Editor’s note: This story has been updated to add that Zogenix resubmitted a new drug application for Fintepla to the FDA in late September.
Treatment with Fintepla (ZX008) can provide a clinically meaningful and profound reduction in the frequency of seizures in Dravet syndrome patients, according to data from two Phase 3 clinical trials.
The most common cause of mortality in Dravet patients is either sudden unexpected death in epilepsy (SUDEP) or status epilepticus (long epileptic episodes). Generalized tonic-clonic seizures (seizures that start in both sides of the brain) are a major risk factor for SUDEP.
Fintepla is a low-dose oral solution of fenfluramine hydrochloride, being developed by Zogenix to treat epileptic seizures linked to Dravet syndrome. Its anti-epileptic properties are associated with the stimulation of serotonin release in the brain.
Researchers assessed the impact of Fintepla in combination with other antiepileptic therapy regimens on generalized tonic-clonic seizures, and focal to bilateral tonic-clonic seizures (which start on one side of the brain and spread to both sides) in children and teenagers with Dravet syndrome.
Results were presented in the poster, “ZX008 Fenfluramine HCl Significantly Reduces Frequency of Generalized Tonic-Clonic Seizures in Dravet Syndrome: Pooled Analysis from Two Phase 3 Clinical Trials,” at the recent 48th Annual meeting of the Child Neurology Society (CNS), held in Charlotte, North Carolina.
Patients not currently on stiripentol (Diacomit, an approved add-on therapy) is were randomized to either placebo or Fintepla at 0.2 or 0.7 mg/kg/day (maximum daily dose of 26 mg/day). Patients being treated with stiripentol were treated with Fintepla at 0.4 mg/kg/day (maximum daily dose of 17 mg/day).
Fintepla’s use resulted in clinically meaningful (defined as a greater than 50% reduction) and profound reductions in the frequency of both generalized tonic-clonic and focal-to-bilateral tonic-clonic seizures.
Specifically, the frequency of focal-to-bilateral tonic-clonic seizures was reduced by 97%, 33%, and 69% in patients given Fintepla at 0.7, 0.4, and 0.2 mg/kg/day, respectively, and fell by 39% in the placebo group. (Abstract of study is on page S59; values match more recent poster data.)
The most common treatment-related side effects included decreased appetite, lack of energy, fatigue, drowsiness, and diarrhea. No cases of cardiac valvular disease or pulmonary arterial hypertension were seen.
“[Fintepla] may represent an important, effective new treatment option for patients with Dravet syndrome,” the researchers wrote.
After an initial refusal by the U.S. Food and Drug Administration (FDA) to review its application requesting Fintepla’s approval — due to incomplete submission of early studies and an accuracy problem in one clinical data set — Zogenix resubmitted its new drug application for Fintepla to the FDA in late September.