The Food and Drug Administration (FDA) has approved Fintepla® (fenfluramine; Zogenix) oral solution for the treatment of seizures associated with Dravet syndrome in patients 2 years of age and older.
An amphetamine derivative, fenfluramine was initially developed as an appetite suppressant and is believed to work through serotonergic mechanisms. The exact mechanism by which fenfluramine exerts its therapeutic effects in Dravet syndrome is unknown.
The effectiveness of fenfluramine was established in 2 double-blind, placebo-controlled trials in patients 2 to 18 years of age (N=202) with a clinical diagnosis of Dravet syndrome who were inadequately controlled on at least 1 antiepileptic drug or other antiseizure treatment (including vagal nerve stimulation or ketogenic diet). In both studies, the primary end point was the change from baseline in the frequency of convulsive seizures per 28 days; the median longest interval between convulsive seizures was also assessed.
Results showed a statistically significantly greater reduction in convulsive seizure frequency with fenfluramine (at doses of 0.2mg/kg/day, 0.4mg/kg/day, and 0.7mg/kg/day) compared with placebo. Moreover, a reduction in convulsive seizure frequency was observed within 3-4 weeks of initiating treatment, and this effect was found to be consistent over the treatment period (14 weeks in Study 1 and 15 weeks in Study 2). Additionally, fenfluramine use was associated with a statistically significant longer interval between convulsive seizures when compared with placebo.
As for safety, the most common adverse reactions associated with treatment included decreased appetite, somnolence, sedation, lethargy, diarrhea, constipation, abnormal echocardiogram, fatigue, malaise, asthenia, ataxia, balance disorder, gait disturbance, blood pressure increased, drooling, salivary hypersecretion; pyrexia, upper respiratory tract infection, vomiting, decreased weight, fall, and status epilepticus.
Fintepla carries a Boxed Warning regarding the risks of valvular heart disease and pulmonary arterial hypertension. Prior to initiating treatment, patients must undergo an echocardiogram to evaluate for these conditions; the test should be repeated every 6 months, and once 3 to 6 months after treatment is completed. Due to these potential risks, the drug is only available through a restricted distribution program called the Fintepla REMS program. According to trial data of up to 3 years duration, no patient receiving Fintepla developed valvular heart disease or pulmonary arterial hypertension.
Fintepla, a Schedule IV controlled substance, is supplied as a cherry-flavored oral solution containing 2.2mg/mL of fenfluramine in 30mL and 360mL bottles. The treatment is expected to be available through Zogenix’s specialty pharmacy partner by the end of July.
For more information visit fintepla.com.