Fintepla (fenfluramine) - 2 Indications

Scroll down for more information on each indication:

• seizures associated with Dravet syndrome in patients 2 years of age and older; approved June of 2020
• seizures associated with Lennox-Gastaut syndrome in patients 2 years of age and older; approved March of 2022

General Information

Fintepla (fenfluramine) is a selective serotonin reuptake inhibitor.

Fintepla is specifically indicated for:

• the treatment of seizures associated with Dravet syndrome in patients 2 years of age and older
• the treatment of seizures associated with Lennox-Gastaut syndrome in patients 2 years of age and older

Fintepla is supplied as an oral solution. Scroll down for the recommended dosing/administration for each indication.

Mechanism of Action

Fintepla (fenfluramine) is a selective serotonin reuptake inhibitor. The mechanisms by which fenfluramine exerts its therapeutic effects in the treatment of seizures associated with Dravet syndrome are unknown. Fenfluramine and the metabolite, norfenfluramine, increase extracellular levels of serotonin through interaction with serotonin transporter proteins, and exhibit agonist activity at serotonin 5HT-2 receptors.

Side Effects

Adverse effects associated with the use of Fintepla may include, but are not limited to, the following:

• 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
• status epilepticus

The Fintepla drug label comes with the following Black Box Warning: There is an association between serotonergic drugs with 5-HT2B receptor agonist activity, including fenfluramine (the active ingredient in Fintepla), and valvular heart disease and pulmonary arterial hypertension. Echocardiogram assessments are required before, during, and after treatment with Fintepla. Fintepla is available only through a restricted program called the Fintepla REMS. 

Indication 1 - Dravat Syndrome

approved June of 2020

Dosing/Administration

The initial starting and maintenance dosage is 0.1 mg/kg twice daily, which can be increased weekly based on efficacy and tolerability. Please see the drug label for the recommended titration schedule, if needed.

• Patients not on concomitant stiripentol who are tolerating Fintepla at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.35 mg/kg twice daily (maximum daily dosage of 26 mg).
• Patients taking concomitant stiripentol and clobazam who are tolerating Fintepla at 0.1 mg/kg twice daily and require further reduction of seizures may benefit from a dosage increase up to a maximum recommended maintenance dosage of 0.2 mg/kg twice daily (maximum daily dosage of 17 mg).

Clinical Trial Results

The FDA approval of Fintepla for Dravat Syndrome was based on two randomized, double-blind, placebo controlled trials in patients 2 to 18 years of age. Study 1 (N=117) compared a 0.7 mg/kg/day and a 0.2 mg/kg/day dose of Fintepla with placebo in patients who were not receiving stiripentol. Study 2 (N=85) compared a 0.4 mg/kg/day dose of Fintepla with placebo in patients who were receiving stiripentol and either clobazam, valproate, or both. In both studies, patients had a clinical diagnosis of Dravet syndrome and were inadequately controlled on at least one AED or other antiseizure treatment including vagal nerve stimulation or a ketogenic diet. Both trials had a 6-week baseline period, during which patients were required to have a minimum of 6 convulsive seizures while on stable AED therapy. The baseline period was followed by randomization into a 2-week (Study 1) or 3-week (Study 2) titration period and a subsequent 12-week maintenance period, where the dose of Fintepla remained stable. The primary efficacy endpoint in both studies was the change from baseline in the frequency of convulsive seizures per 28 days during the combined 14-week (Study 1) or 15-week (Study 2) titration and maintenance periods (i.e., treatment period).

In Study 1 and Study 2, the reduction in convulsive seizure frequency per 28 days was statistically significantly greater for all dose groups of Fintepla compared to placebo. A reduction in convulsive seizures was observed within 3 to 4 weeks of starting Fintepla, and the effect remained generally consistent over the 14- or 15-week treatment period.

Indication 2 - Lennox-Gastaut syndrome

approved March of 2022

Dosing/Administration

The initial starting dosage is 0.1 mg/kg twice daily, which should be increased weekly based on tolerability.

• Patients not on concomitant stiripentol: The recommended maintenance dosage of Fintepla is 0.35 mg/kg twice daily (maximum daily dosage of 26 mg).
• Patients taking concomitant stiripentol plus clobazam: the recommended maintenance dosage is 0.2 mg/kg twice daily (maximum daily dosage of 17 mg).

Clinical Trial Results

The FDA approval was based on safety and efficacy data from a global, randomized, placebo-controlled Phase 3 clinical trial in 263 patients with LGS (age 2-35 years). Data demonstrated that fenfluramine at a dose of 0.7/mg/kg/day significantly reduced the frequency of drop seizures compared to placebo. Nearly a fourth of those patients on fenfluramine 0.7 mg/kg/day experienced a ≥50% reduction in drop seizure frequency per 28 days; 18% with >50 to <75% reduction and 6% >75% reduction.