Fenfluramine a promising long-term treatment option for Lennox-Gastaut syndrome

Treatment with fenfluramine produces sustained reductions in drop seizure frequency, especially generalized tonic-clonic seizures, in patients with Lennox-Gastaut syndrome (LGS), according to the results of an open-label extension trial.

The trial included LGS patients who completed a 14-week phase III randomized clinical trial. All patients received 0.2-mg/kg/day fenfluramine initially, with the treatment dose titrated after 1 month to provide adequate efficacy while minimizing risk. Researchers assessed efficacy and tolerability at 3-month intervals.

A total of 247 patients (mean age 14.3 years, 32 percent adults) were enrolled in the OLE, with median fenfluramine treatment duration of 364 days. Most (88.3 percent) patients received 2–4 concomitant antiseizure medications.

Monthly drop seizure frequency decreased by a median of 28.6 percent over the entire open-label extension (OLE; n=241) and by a median of 50.5 percent at month 15 (n=142; p<0.0001). There were 75 patients (31.1 percent) who achieved a ≥50-percent reduction in drop seizure frequency. On the other hand, nondrop seizure frequency decreased by 45.9 percent (n=192; p=0.0038).

The greatest response to treatment was seen for generalized tonic-clonic seizures and tonic seizures, with median reductions of 48.8 percent (p<0.0001; n=106) and 35.8 percent (p<0.0001; n=186), respectively, over the entire OLE.

There were 37.6 percent (95 percent confidence interval [CI], 31.4–44.1; n=237) of investigators and 35.2 percent of caregivers (95 percent CI, 29.1–41.8; n=230) who rated patients as “much improved” or “very much improved” on the Clinical Global Impression of Improvement scale.

The most common treatment-emergent adverse events were decreased appetite (16.2 percent) and fatigue (13.4 percent). None of the patients developed valvular heart disease (VHD) or pulmonary arterial hypertension (PAH).

Based on the findings, fenfluramine is posed as an important long-term treatment option for LGS.