Efficacy, tolerability, and retention of fenfluramine for the treatment of seizures in patients with Dravet syndrome: Compassionate use program in Germany.

Abstract

Dravet syndrome (DS) is a rare but severe drug-resistant epilepsy. Before the approval of fenfluramine (FFA) for the treatment of seizures in DS, patients in Germany could receive treatment under a compassionate use program (CUP). We conducted a multicenter, retrospective, observational study to describe the efficacy, tolerability, and retention of FFA within the CUP. Patients received add-on therapy with oral FFA gradually titrated to a target dose between .13 and .7mg/kg/day. Overall, 78 patients with DS (median age = 8.0 years, range = 2.1-46.0; 53% female, median concomitant antiseizure medications [ASMs] = 3) were treated with FFA for a median duration of 255.5days (range = 31-572). Responder rates (a ≥50% reduction; n=78) and seizure-freedom rates at 3months were 68% and 14% for total seizures, respectively, and 67% and 23% for generalized tonic-clonic seizures. Responder rates were consistent at 6 and 12months (n=66 and n=43, respectively). Median seizure days per month significantly decreased from 10.0 (range = .5-30) to 3.0 (range = 0-30) in the 3-month period before and after FFA treatment (p<.001). Significantly fewer patients reported at least one episode of status epilepticus (28% vs. 14% patients before and after FFA initiation, p=.005). During FFA treatment, 35 (45%) patients were able to discontinue a concomitant ASM. At the last follow-up date, 66 (85%) patients remained on treatment with FFA. The most common adverse events were somnolence (36%), decreased appetite (22%), and ataxia (8%). Forty-eight (62%) patients were reported as having a meaningful global clinical improvement. In a large cohort of patients, FFA demonstrated efficacy across a range of outcomes including clinically significant reductions in convulsive seizures, and was well tolerated, providing valuable information for real-world practice.