The European Medicines Agency (EMA) designated Diacomit an orphan drug for Dravet syndrome in 2001 and approved its use in the EU in 2007. It recommends Diacomit as a complement to Onfi (clobazam) and Depacon (sodium valproate)
Diacomit was approved by the U.S. Food and Drug Administration (FDA) in August 2018 as an add-on therapy alongside Onfi in children ages 2 and older. In September 2022, the FDA extended this approval to children as young as 6 months who weight at least 7 kg (about 15 lbs).
How Diacomit works
Diacomit has two different mechanisms of action.
The first is an effect on GABAA receptors. GABA is a neurotransmitter — a signaling molecule in the brain — that inhibits brain cell activity. GABA acts by binding to GABA receptors like GABAA. Diacomit can also bind to GABAA receptors, blocking neurons in the same way GABA does. (Seizures are thought to be the result of excessive brain cell activity; it is hoped that by inhibiting this activity, they can be stopped).
Diacomit also inhibits an enzyme called cytochrome P450. This enzyme degrades toxic substances in the body, and can also degrade pharmaceutical agents such as clobazam. When Diacomit is used as add-on therapy, clobazam levels in the blood are higher and the treatment can be more effective.
Diacomit in clinical trials
Two independent Phase 3 double-blind, placebo-controlled, and randomized trials in France (STICLO-France) and in Italy (STICLO-Italy) assessed the efficacy and safety of Diacomit as an additional therapy to Onfi and Depacon. There were 42 children with Dravet syndrome in the SILCO-France study and 23 in the SILCO-Italy study.
In both trials, patients received Onfi and Depacon during a one-month baseline period. They were then randomized to either 50 mg per kg of Diacomit per day, or a placebo, in addition to Onfi and Depacon for two months. After the double-blind period, all were given the Diacomit combination in an open-label phase that ran for 30 days. Patients who experienced at least a 50 percent reduction in the frequency of clonic seizures were classified as responders.
In the STICLO-France trial, 71 percent of patients responded to treatment in the Diacomit group, and one patient (5 percent of all participants) in the placebo group. Forty-three percent of patients in the Diacomit group, but none in the placebo group, were free of seizures after two months. In the STICLO-Italy trial, 67 percent of patients in the Diacomit group responded to treatment, compared to 9 percent in the placebo group.
Another study assessed the efficacy of Diacomit in addition to Onfi and Depacon in patients with and without mutations in the SCN1A gene. The SCN1A gene provides instructions to build the NaV1.1 sub-unit of sodium channels and is mutated in 70 to 85 percent of all Dravet patients. Fifteen patients carrying a known SCN1A mutation and 17 without reported SCN1A mutations received Diacomit as an adjunctive therapy for four weeks. Their seizure frequency decreased by 72.53 percent in the mutation group and 50.58 percent in the non-mutation group.
More recent studies in Japan, published in the journal Epilepsy Research, supported the short- and long-term use of Diacomit as an add-on therapy in Dravet syndrome. The study enrolled 24 patients to receive Diacomit alongside either Onfi or Depacon. Significantly more patients responded to Diacomit compared to placebo, with at least a 50 percent reduction in clonic and tonic-clonic seizures compared to baseline. These results were sustained long-term, with a similar response rate seen after 56 weeks of treatment.
The most common adverse events associated with Diacomit therapy are drowsiness and loss of appetite, which can result in weight loss.
Diacomit has an expanded access status at the Cook Children’s Medical Center in Fort Worth, Texas, the Cincinnati Children’s Hospital Medical Center in Cincinnati, Ohio, and the Children’s Hospital Colorado in Aurora, Colorado. More information can be found at ClinicalTrials.gov.
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