The study, “Stiripentol: A Novel Antiseizure Medication for the Management of Dravet Syndrome,” was published in the journal Annals of Pharmacotherapy.
Dravet syndrome is a severe type of epilepsy which usually manifests during the first year of life and is characterized by seizures, cognitive deficits, and increased mortality. Treatments are focused on reducing the frequency and duration of seizures, and, in particular, on helping to prevent and manage long epileptic episodes known as status epilepticus.
“Unfortunately, often, it is not possible to eliminate all seizures, even with combination therapy,” the researchers wrote.
Diacomit, marketed by Biocodex, is a new type of anticonvulsive medication that has been shown to reduce the frequency of seizures in patients with Dravet syndrome, especially when administered in combination with other antiseizure medications, such as Onfi (clobazam), Depacon (valproate), and topiramate (sold as Topamax among other names), or with dietary interventions such as the ketogenic diet (low-carbohydrate, high-fat diet).
This new antiseizure therapy received the designation of orphan drug in 2001 from the European Medicines Agency, followed by its approval in Europe as an add-on therapy in 2007. The U.S. Food and Drug Administration approved Diacomit in 2018 as an add-on therapy for the treatment of seizures in children with Dravet syndrome who are 2 years of age or older and already taking Onfi.
In the study, researchers from the University of Virginia reviewed the chemical properties, mode of action, safety, and efficacy of Diacomit to control refractory seizures (seizures that do not respond to standard anti-epileptic medications) in patients with Dravet syndrome and other types of drug-resistant epilepsies.
They analyzed data from relevant studies published between 1978 and April 2019, including observational and retrospective studies, as well as Phase 1, 2, and 3 clinical trials.
Diacomit has two different effects on the brain’s GABAergic system — the main system that is responsible for preventing excessive neuronal activity, which is at the root of many types of epilepsy, including Dravet syndrome.
The medication helps increase the levels of GABA — the main inhibitory neural signal in the brain — by preventing its re-uptake in the brain. At the same time, Diacomit stimulates the activity of GABAA receptors — the channels located on the surface of neurons where GABA passes through to reach brain cells — which results in additional stimulating of the brain’s inhibitory GABAergic system.
Several studies have shown that Diacomit is well-absorbed by the body when administered orally, reaching a maximal concentration in the plasma within two to three hours after its administration.
In clinical trials — including two placebo-controlled Phase 3 trials called STICLO-France and STICLO-Italy, and several open-label studies — Diacomit showed potential in managing Dravet seizures when used in combination with Onfi and Depacon. Frequency of seizures was reduced by 50% or more in approximately 40%–70% of patients with Dravet syndrome. Some studies also reported that Diacomit reduced the duration of seizures and the number of status epilepticus episodes.
In general, clinical data showed that the oral therapy was well-tolerated. The most common adverse effects linked to Diacomit use include somnolence (sleepiness), decreased appetite, low white blood cell counts, and low platelet levels.
“[Diacomit] is an effective adjunctive therapy for reducing the frequency and duration of refractory seizures in patients with Dravet syndrome,” the researchers said.
“Additional research is currently underway to identify clinically significant drug interactions, better define optimal dosing in adults with Dravet syndrome, and determine the role of [the therapy] in other refractory epilepsies.”