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The National Institute for Health and Care Excellence (NICE) has issued final draft guidance recommending fenfluramine (Fintepla) for treating seizures associated with Lennox-Gastaut syndrome. The recommendation applies to patients aged ≥ 2 years.

Fenfluramine is approved as an add-on to other antiseizure medications. Its use is contingent on achieving ≥ 30% reduction in seizures at biannual checkups. The drug must also be available at a discount through a commercial arrangement with the National Health Service (NHS) England.

This decision follows an appeal against NICE’s initial rejection of fenfluramine in April 2024. The original decision cited uncertainties regarding its clinical efficacy compared with cannabidiol (Epidyolex) plus clobazam, as well as concerns over cost-effectiveness.

While comparative efficacy remains unclear, NICE overturned its decision after reassessing cost data. The updated analysis suggested that both treatment regimens have similar costs, with fenfluramine potentially being the more affordable option.

Stephen Powis, MBA, PhD, national medical director for NHS England, said in a press release: “Fenfluramine will offer a vital alternative for those who can’t tolerate existing cannabis-based treatment.”

Lennox-Gastaut Syndrome

Lennox-Gastaut syndrome is a chronic, treatment-resistant form of epilepsy that typically starts before the age of 8 years. It is characterised by a distinct electroencephalogram pattern and developmental delay or cognitive impairment.

Patients experience frequent seizures, including ‘drop seizures’ which result in a loss of muscle tone and stiffening of muscles, and generalised tonic-clonic seizures, which involve muscle jerking and loss of consciousness.

Around 60,000 children in England have epilepsy, of whom between 1% and 2% are estimated to have Lennox-Gastaut syndrome.

Fenfluramine works by increasing extracellular serotonin levels and acts as a serotonergic 5-hydroxytryptamine 2 receptor agonist and sigma-1 receptor antagonist. How the drug produces anti-epileptic effects remains unclear.

Clinical Trial Evidence

The primary evidence for fenfluramine came from Study 1601, a phase 3, randomised control trial involving 247 patients aged 2-35 years with Lennox-Gastaut syndrome. 

Participants started with 0.2 mg/kg/day fenfluramine. After 1 month, doses were titrated according to effectiveness and tolerability, assessed every 3 months. Patients were treated for a median of 364 days. Almost 90% of patients received 2-4 concomitant antiseizure medications.

Results showed a 28.6% reduction in monthly drop seizure frequency. Additionally, 31.1% of patients experienced a reduction of more than 50.0% in drop seizures. Other seizure types also decreased, with median reductions of 45.9% for non-drop seizures and 48.8% for generalised tonic-clonic seizures.

Around 36% of caregivers and investigators rated patients as “much improved” or “very much improved” on the Clinical Global Impression of Improvement scale.

The most common adverse events included decreased appetite and fatigue. The study reported no cases of valvular heart disease or pulmonary arterial hypertension.

Fenfluramine is an oral liquid medicine. Its Summary of Product Characteristics recommends starting at 0.2 mg/kg/day and gradually increasing to a maintenance dose of 0.7 mg/lg/day at day 14. The maximum recommended dose is 26 mg when taken without stiripentol, and 17 mg when taken with it.

Fenfluramine’s list price is £1802 for a 120-mL (2.2 mg/mL) bottle and £5408 for a 360-mL bottle. The manufacture, UCB, has a commercial arrangement with the NHS, making it available at a discount.

Improving Quality of Life

Commenting on NICE’s decision in a statement, Ley Sander, MD, PhD, medical director at the Epilepsy Society said: “Most people with this syndrome don’t achieve complete seizure freedom, but this will improve their quality of life.

“Given the limited therapeutic options currently available for Lennox-Gastaut syndrome, this approval offers a significant source of hope for affected families.”

Annie Lennon is a medical journalist. Her writing appears on Medscape.co.uk, Medical News Today, and Psych Central, among other outlets.