Fenfluramine safe, effective in reducing drop seizures in Lennox-Gastaut syndrome
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Patients with Lennox-Gastaut syndrome experienced a significant reduction in drop seizures with fenfluramine, according to results of a clinical trial published in JAMA Neurology.
“Most patients with [Lennox-Gastaut syndrome (LGS)] develop between three and five seizure types that wax and wane during disease progression,” Kelly G. Knupp, MD, MSCS, a neurologist at Children’s Hospital Colorado, and colleagues wrote. “Convulsive seizures (e.g., generalized tonic-clonic seizures) are also commonly observed and usually occur in later stages of LGS but sometimes may precede core seizure types.”
Knupp and colleagues sought to evaluate the safety and efficacy of fenfluramine as a new treatment option in LGS patients, and conducted a double-blind, placebo-controlled randomized 20-week clinical trial. They enrolled 263 patients (median age, 13 years; 56% men) with confirmed diagnosis of LGS who experienced two or more drop seizures per week during a 4-week baseline period at 65 sites across North America, Europe and Australia.
Participants received either 0.7 mg/kg per day or 0.2 mg/kg per day (maximum 26 mg per day) of fenfluramine or placebo, which they took for 12 weeks, following a 2-week titration interval.
The primary outcome was percentage change from baseline in drop seizure frequency in patients who received 0.7 mg/kg per day of fenfluramine compared with placebo.
Knupp and colleagues reported there was a median percentage reduction in frequency of drop seizures of 26.5 percentage points in the 0.7 mg/kg fenfluramine group, 14.2 percentage points in the 0.2 mg/kg fenfluramine group and 7.6 percentage points in the placebo group.
In addition, patients in the 0.7 mg/kg fenfluramine group achieved an estimated median difference in drop seizures of 19.9 percentage points (95% CI, 31.0 to 8.7) from baseline compared with placebo, which met the trial’s primary outcome.
Generalized tonic-clonic seizures, which were observed in 120 of 263 patients, were determined to be most responsive to fenfluramine, with a decrease in frequency of 45.7% in the 0.7 mg/kg fenfluramine group and 58.2% in the 0.2 mg/kg group, compared with an increase of 3.7% in the placebo group.
The most common treatment-emergent adverse events were decreased appetite, sleepiness and fatigue. Investigators did not observe valvular heart disease or pulmonary arterial hypertension in any participants.
“The findings reinforce the clinical profile of [fenfluramine] and its value as a new and important treatment option for [LGS] patients two years of age and older,” Knupp told Healio. “The data show that [fenfluramine] 0.7 mg/kg/day, in combination with a patient’s current anti-epileptic treatment regimen for seizures associated with LGS, is effective in reducing the frequency of seizures associated with drop seizures compared to placebo, particularly for those experiencing generalized tonic-clonic seizures, which often result in bodily injury and hospitalizations and increase risk for [sudden, unexpected death in epilepsy patients].”
[Editor’s Note: This story was updated to include original comments from Knupp.]