Favourable opinion for reimbursement 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, only in last-resort situations.
Unfavourable opinion for reimbursement in the other situations covered by the MA indication.
Clinical Benefit
Substantial
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.
Insufficient
The clinical benefit of FINTEPLA (fenfluramine) is insufficient to justify public funding in view of the available alternatives in the other MA situations.
Clinical Added Value
minor
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.
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