FDA Approves Diacomit

On August 20, 2018, the U.S. Food and Drug Administration (FDA) approved Diacomit (stiripentol) for seizures associated with Dravet syndrome in patients 2 years of age and older taking clobazam.

Dravet syndrome is a rare genetic condition that usually appears during the first year of life with prolonged fever-related seizures. Later, other types of seizures typically appear, and additionally, status epilepticus, a potentially life-threatening state of continuous seizure activity requiring emergency medical care, may occur. Children with Dravet syndrome typically experience poor development of language and motor skills, hyperactivity, and difficulty relating to others.

The efficacy of Diacomit was established in two multicenter placebo-controlled double-blind randomized studies (Study 1 and Study 2). Patients enrolled in the studies were required to be aged between 3 years and under 18 years with Dravet syndrome that was inadequately controlled with clobazam and valproate, and experiencing at least 4 generalized clonic or tonic-clonic seizures per month.

After a 1-month baseline period where patients continued to receive clobazam and valproate, they were then randomly selected to receive additional treatment with either Diacomit or placebo for a double-blind period of two months.

The primary efficacy endpoint for both studies was the responder rate – a responder being a patient who experienced more than 50% decrease in the frequency of seizures per month during the two month double-blind period compared to the one month baseline period.

In both studies, the responder rate was significantly greater for Diacomit than for placebo. In Study 1 (N=41), 71% of Diacomit patients (N=21) were responders, compared to 5% of patients taking the placebo (N=20), and 43% of patients reported no generalized clonic or tonic-clonic seizure during the duration of the study. In Study 2 (N=23), 67% of Diacomit patients (N=12) were responders, compared to 9.1% of patients taking the placebo (N=11), and 25% of patients reported no seizures.

The exact mechanism of action by which Diacomit exerts its anticonvulsant effect in humans is unknown, but possible actions include direct effects mediated through GABAA receptors and indirect effects involving inhibition of CYP450 activity.

Common side effects (occurring in at least 10% of Diacomit-treated patients) included somnolence (sleepiness and drowsiness), decreased appetite, agitation, ataxia (impaired coordination and balance), weight decreased, hypotonia (low muscle tone), nausea, tremor, dysarthria (difficulty speaking words; difficulty forming words during speech), and insomnia.

Diacomit will be available as oral capsules and powder for oral suspension, and prescriptions must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks. As is true for many other drugs that treat epilepsy, the most serious risks include thoughts about suicide, attempts to commit suicide, feelings of agitation, new or worsening depression, aggression, and panic attacks.

Posted: August 2018

Diacomit (stiripentol) FDA Approval History

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