FINTEPLA (fenfluramine) - Epilepsy

The clinical benefit of FINTEPLA (fenfluramine) is substantial in the treatment of seizures associated with Dravet syndrome as an add-on therapy to other anti-epileptic medicines for drug-resistant patients 2 years of age and older, only in last-resort situations.

Considering:

• initial data having demonstrated the superiority of fenfluramine compared to placebo, as add-on therapy, in two double-blind, randomised studies (including one study in combination with stiripentol plus clobazam and/or sodium valproate), in children and adolescents with Dravet syndrome,
  • with respect to the mean change in total seizure frequency in the short term over 14 and 15 weeks (primary endpoint), with a 54 to 62% reduction, for a mean number of seizures at baseline ranging from 22 to 45 seizures per month, respectively
  • with respect to the percentage of patients responding to treatment (i.e. ≥ 50% reduction in seizures) and the seizure-free interval over 14 and 15 weeks, ranked secondary endpoints,
• new comparative efficacy data versus placebo issues from a study with a similar methodology having reported similar results for these endpoints,
• the medical need that remains substantial, due to the limited alternatives in this rare disease,
• the absence of robust indirect comparative data versus cannabidiol (EPIDYOLEX) in a concomitant development context,

but:

• the absence of robust data on quality of life,
• the safety profile with abnormal echocardiographic events (all trace mitral and/or aortic valve regurgitations and one case of mild mitral valve regurgitation) reported during short-term studies (16.4% in the fenfluramine groups versus 6.0% in the placebo groups) at the time of initial inclusion,
• the risk of pulmonary arterial hypertension now classed as an important identified risk following a post-marketing case, justifying the maintenance of supervision along with the need for echocardiogram monitoring, taking into account the history of the drug in the obesity indication in adults,
• the absence of long-term efficacy and safety data for fenfluramine, particularly in terms of the impact on the neurocognitive deterioration and psychomotor development of patients, in the context of a chronic disease,

the Committee deems that FINTEPLA (fenfluramine) provides a minor clinical added value (CAV IV) in the current last-resort care pathway for the treatment of seizures associated with Dravet syndrome as an add-on therapy to other anti-epileptic medicines for drug-resistant patients 2 years of age and older.