EU Approves Fintepla for Lennox-Gastaut-Related Seizures

EU Approves Fintepla for Lennox-Gastaut-Related Seizures

Rare Daily Staff

The European Union approved Fintepla for the treatment of seizures associated with Lennox-Gastaut syndrome as an add-on therapy to other anti-epileptic medicines for patients two years of age and older.

Lennox-Gastaut syndrome (LGS) is a severe childhood-onset developmental and epileptic encephalopathy characterized by multiple types of drug-resistant seizures with high morbidity, as well as serious impairment of neurodevelopmental, cognitive, and motor functions. Seizures leading to falls are common in LGS and tonic seizures are a hallmark feature of this syndrome. In addition, convulsive seizures, such as 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.

Fintepla is an oral solution of fenfluramine. It was developed by Zogenix, which UCB acquired in March 2022. Fenfluramine is a serotonin releasing agent that stimulates multiple 5-HT receptor sub-types through the release of serotonin. Fenfluramine may reduce seizures by acting as an agonist at specific serotonin receptors in the brain, including the 5-HT1D, 5-HT2A, and 5-HT2C receptors, and also by acting on the sigma-1 receptor. The precise mode of action of fenfluramine in LGS is not known.

The approval by the European Commission 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), which demonstrated adjunctive fenfluramine provided a significantly greater reduction in the frequency of drop seizures compared to placebo. The most common treatment-emergent adverse events were decreased appetite, somnolence, fatigue, and fever. No cases of valvular heart disease or pulmonary arterial hypertension were observed.

“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,” said Rima Nabbout, professor of Pediatric Neurology at University and director of the French reference center for rare epilepsies at Necker Enfants Malades Hospital in Paris. “Seizures are often resistant to currently available medications, making this approval especially important for the individuals affected and their families.”

The European Commission has also adopted the EMA Committee for Orphan Medicinal Products recommendation that the orphan designation for fenfluramine be maintained.

Photo: Rima Nabbout, professor of Pediatric Neurology at University and director of the French reference center for rare epilepsies at Necker Enfants Malades Hospital in Paris.