FINTEPLA®▼ (fenfluramine) oral solution recommended for approval in the EU
- Recommendation based on Phase 3 study data demonstrating safety and efficacy in the most difficult to treat seizure types, including drop seizures1,2
- LGS is a rare severe form of epilepsy that typically starts during childhood and persists into adulthood. It is characterized by multiple types of drug-resistant seizures with high morbidity3,4 as well as serious impairment of neurodevelopmental, cognitive, and motor functions4
UCB, a global biopharmaceutical company, announced on 19th December 2022 that FINTEPLA®▼ (fenfluramine) oral solution has been recommended for marketing authorisation in the European Union (EU) for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) as an add-on therapy to other anti-epileptic medicines for patients 2 years of age and older. Fenfluramine is already approved in the US for the treatment of seizures associated with Lennox- Gastaut syndrome. In addition, it is also approved for the treatment of seizures associated with Dravet syndrome in the EU*, US, and Japan.5,6,7
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its positive opinion on safety and efficacy data from a global, randomised, placebo-controlled Phase 3 clinical trial, in 263 patients with LGS (aged 2-35 years), that demonstrated adjunctive fenfluramine at a dose of 0.7/mg/kg/day, provided a significantly greater reduction in the frequency of drop seizures (p=0.001) compared to placebo.1 The most common treatment-emergent adverse events were decreased appetite, somnolence, fatigue and pyrexia.1 No cases of valvular heart disease or pulmonary arterial hypertension were observed.1
The CHMP’s positive opinion on fenfluramine will be referred to the European Commission (EC), which will deliver a final decision in Q1 2023.
“This positive CHMP opinion is a significant regulatory milestone towards providing a new treatment option to individuals – and their families – living with this rare epilepsy in the EU,” said Mike Davis, Head of Global Epilepsy & Rare Syndromes, UCB. “We’re delighted by this recommendation, highlighting our ongoing commitment to the LGS community by ensuring we bring differentiated medicines to those with unmet needs.”
Additional data supporting the safety and efficacy of fenfluramine in LGS in the open label extension (OLE) part of the study was recently published in Epilepsia showing fenfluramine, when added to a patient’s current anti-epileptic treatment regimen for seizures associated with LGS, was effective in reducing the frequency of multiple seizure types and was generally well tolerated during a median treatment duration of 364 days.2 Study participants experienced a sustained reduction in the frequency of motor seizures including those that resulted in a drop or fall (Generalised Tonic-Clonic Seizures (GTCS), secondary GTCS (SGTC; focal to bilateral tonic-clonic), tonic seizures, atonic seizures, and tonic-atonic seizures).2 In the OLE phase, the most common treatment-emergent adverse events were decreased appetite, fatigue, nasopharyngitis and seizure. The cardiovascular safety in this study further corroborates the fenfluramine safety profiles observed; no cases of valvular heart disease or pulmonary arterial hypertension were observed. 2
LGS is a severe childhood-onset developmental and epileptic encephalopathy (DEE) characterised by multiple types of drug-refractory seizures with high morbidity3,4 as well as serious impairment of neurodevelopmental, cognitive, and motor functions.4 LGS affects an estimated 2 in 10,000 people in European Union (EU).8 LGS has far-reaching effects beyond seizures, including issues with developmental communication, psychiatric symptoms, sleep, behavioural challenges, and mobility.9 Drop seizures are hallmark features of LGS, particularly tonic seizures. Convulsive seizures (eg, generalised tonic-clonic [GTC] seizures) are also commonly observed and usually occur in later stages of LGS but sometimes may precede core seizure types. In addition to being associated with bodily injury and hospitalisations, GTC seizures are a primary risk factor of sudden unexpected death in epilepsy (SUDEP). Patients with GTC seizures have an approximately 10-fold greater risk for SUDEP than patients with other seizure types.5
▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
- Knupp K, Scheffer I, Ceulemans B, et al. Efficacy and safety of fenfluramine for the treatment of seizures associated with Lennox-Gastaut syndrome. A Randomized Clinical Trial. JAMA Neurol. 2022;79(6):554-564
- Knupp K, Scheffer I, Ceulemans B, et al. Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox-Gastaut syndrome: interim analysis of an open-label extension study. Epilepsia. 2022; doi: 10.1111/epi.17431
- Strzelczyk A, Schubert-Bast S. Expanding the Treatment Landscape for Lennox-Gastaut Syndrome: Current and Future Strategies. CNS Drugs. 2021;35(1):61-83.
- Specchio, N, Wirrell, EC, Scheffer, IE, Nabbout, R, Riney, K, Samia, P, et al. International League Against Epilepsy classification and definition of epilepsy syndromes with onset in childhood: Position paper by the ILAE Task Force on Nosology and Definitions. Epilepsia. 2022;63:1398– 1442.
- Fintepla EMA SmPC https://www.ema.europa.eu/en/documents/product-information/fintepla-epar-product-information_en.pdf Accessed December 2022
- Fintepla US PI https://www.ucb-usa.com/fintepla-prescribing-information.pdf Accessed December 2022
- Fintepla Japan PI. September 2022. フィンテプラ内用液2.2mg/mL (pmda.go.jp). Accessed December 2022
- EMA. EU/3/17/1855 : Orphan designation for the treatment of Lennox-Gastaut syndrome https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3171855#:~:text=At%20the%20time%20of%20designation,is%205%20people%20in%2010%2C000. Accessed December 2022
- LGS Foundation. LGS Characteristics and Major Concerns Survey. https://www.lgsfoundation.org/wp-content/uploads/2021/08/2019-PFDD-Caregiver-Survey-1.pdf. Accessed December