FINTEPLA®▼ (fenfluramine) oral solution approved in the EU for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS)

The approval by the European Commission (EC) was based on safety and efficacy data from a global, randomized, 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. The most common treatment-emergent adverse events were decreased appetite, somnolence, fatigue, and pyrexia (fever). No cases of valvular heart disease or pulmonary arterial hypertension were observed. (2)

Professor Rima Nabbout, MD, PhD, Professor of Paediatric Neurology at University Paris cité, APHP, Necker Enfants Malades, Institut Imagine, Paris, France, said: “LGS is a developmental and epileptic encephalopathy where seizures are frequent, inducing high level of trauma injuries and negatively impacting development and quality of life. Seizures are often resistant to currently available medications, making this approval especially important for the individuals affected and their families.”

Mike Davis, Head of Global Epilepsy & Rare Syndromes, UCB, said: “With this approval, fenfluramine is now an important additional treatment option for those impacted by this difficult to treat condition in Europe. This approval underscores our commitment to improving treatment outcomes, while addressing the high unmet need for new treatments for people living with LGS and rare epilepsies.”

LGS is a severe childhood-onset developmental and epileptic encephalopathy (DEE) characterized by multiple types of drug-resistant seizures with high morbidity, as well as serious impairment of neurodevelopmental, cognitive, and motor functions, (3,4) affecting an estimated 2 in 10,000 people in European Union (EU).5 Seizures leading to falls ("drop attacks/seizures") are common in LGS and tonic seizures are a hallmark feature of this syndrome. (3,4) In addition, convulsive seizures (e.g., generalized 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 hospitalizations, 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. (2)

Additionally, the EC has also adopted the EMA Committee for Orphan Medicinal Products (COMP) recommendation that the orphan designation for fenfluramine be maintained. (6)

References:

1. Fintepla EMA PI.  https://ec.europa.eu/health/documents/community-register/2023/20230124158297/anx_158297_en.pdf. Accessed February 2023.

2. 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.

3. Strzelczyk A, Schubert-Bast S. Expanding the Treatment Landscape for Lennox-Gastaut Syndrome: Current and Future Strategies. CNS Drugs. 2021;35(1):61-83.

4. 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.

5. EU/3/17/1836: Orphan designation for the treatment of Lennox-Gastaut syndrome https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3171836. Accessed February 2023.

6. EMA/COMP/946245/2022: Committee for Orphan Medicinal Products (COMP). Minutes for the meeting on 06-08 December 2022. https://www.ema.europa.eu/en/documents/minutes/minutes-comp-meeting-6-8-december-2022_en.pdf. Accessed February 2023.