FDA Approves Diacomit as Add-On Therapy for Dravet Syndrome

FDA Approves Diacomit as Add-On Therapy for Dravet Syndrome

The U.S. Food and Drug Administration (FDA) has approved Biocodex’s Diacomit (stiripentol) as an add-on therapy for seizures associated with Dravet syndrome in patients 2 years and older who are undergoing treatment with Onfi (clobazam), an anticonvulsant therapy marketed by Lundbeck.

Diacomit is used as an adjunctive (add-on) therapy for treating Dravet syndrome, and according to the FDA, no clinical data exists to support its use alone (mono-therapy).

This is the second FDA-approved therapy for Dravet syndrome. In June, GW Pharmaceutical‘s plant-derived cannabinoid Epidiolex also was approved to treat seizures associated with Dravet syndrome in patients 2 and older. The approval also extended to patients with Lennox-Gastaut syndrome, a childhood form of severe epilepsy characterized by multiple types of seizures and intellectual disability.

Diacomit works via two mechanisms: one that targets GABAA receptors and another that inhibits an enzyme called cytochrome P450.

GABAA receptors are the targets of the natural neurotransmitter GABA, a signaling molecule in the brain that inhibits brain cells’ activity. Diacomit targets and binds to GABAreceptors, blocking nerve cells’ (neurons) activity, which can trigger seizures when excessive.

The second mode-of-action of Diacomit is by inhibiting the cytochrome P450. This enzyme degrades toxic substances in the body, but also can degrade pharmaceutical agents such as clobazam, decreasing this agent’s therapeutic potential.

Adding Diacomit to clobazam treatment decreases clobazam degradation, allowing its therapeutic levels to be maintained in the blood so it can be effective.

Diacomit’s safety and efficacy as an add-on therapy to Onfi and AbbVie’s injectable anticonvulsant Depacon (sodium valproate) has been established in two Phase 3 randomized and placebo-controlled trials, one in France (STICLO-France) and one in Italy (STICLO-Italy).

A total of 42 children with Dravet syndrome participated in the SILCO-France study and 23 in the SILCO-Italy study.

In the STICLO-France trial, 71% of patients responded to treatment (defined as 50% or higher reduction in the frequency of clonic seizures) in the Diacomit group, and 43% were seizure-free after two months. In the placebo group, only one patient responded to the treatment and none were free of seizures.

In the STICLO-Italy trial, 67% of patients in the Diacomit group responded to treatment, compared to 9% in the placebo group.

Diacomit as an add-on therapy for four weeks led to a decrease in seizure frequency by 72.53% in patients with mutations in the SCN1A gene (mutated in 70 to 85% of all Dravet patients), and by 50.58% in patients without SCN1A mutations.

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