Dravet syndrome treatment Diacomit may ease status epilepticus
Add-on treatment reduced frequency, may be able to stop episodes, review finds
Add-on treatment with Diacomit (stiripentol) was associated with reductions in the number of episodes of status epilepticus (SE), periods of prolonged seizure activity, in people with Dravet syndrome and other types of epilepsy, a review study found.
Evidence also suggested that Diacomit may be able to stop ongoing SE episodes that aren’t responding to standard treatments, although more research is needed to establish its use for that purpose, the researchers said. “Clinical evidence suggests that [Diacomit] is a well-tolerated and effective therapy that markedly reduces the frequency of SE, and possibly the duration of SE, in Dravet syndrome, and it should be introduced as early as possible in the disease course in order to limit the morbidity [suffering] and mortality associated with SE episodes,” they wrote.
The study, “Efficacy and safety of stiripentol in the prevention and cessation of status epilepticus: A systematic review,” was published in Epilepsia. It was funded by Biocodex, which markets Diacomit.
SE refers to a period of five minutes or more of continuous seizure activity or recurrent seizures without recovery in between. Convulsive SE is seen in almost 90% of Dravet patients, and about half of Dravet patients younger than 2 have frequent episodes, the researchers said.
SE is a serious, life-threatening emergency and is the second-most common cause of mortality in Dravet, according to the researchers. Management of SE often involves an emergency room or hospital visit for treatment, but the condition is commonly resistant to first-line treatment with benzodiazepines such as diazepam, and sometimes second- or third- line treatments as well.
Dravet syndrome treatment benefits
Diacomit is an anti-seizure medication approved in the U.S. and Europe as an add-on to standard Dravet treatments. The therapy modulates the same proteins, called GABA-A receptors, that benzodiazepines do, but in a somewhat different way. Scientists believe that Diacomit could be effective for preventing and terminating SE, including SE that hasn’t responded to benzodiazepines.
The researchers conducted a systematic review of preclinical and clinical studies that have reported on the use of Diacomit for these purposes in Dravet syndrome or other types of epilepsy in which SE occurs. The analysis covered 17 studies, of which 15 were clinical and two were preclinical rodent studies. Of the human studies, 12 investigated Diacomit’s ability to prevent SE, 11 of which included Dravet patients. The studies involved anywhere from three to 131 patients, most of whom were children.
Across these studies, at least 26% of patients saw a reduction in SE events after starting Diacomit, with 41% to 100% seeing at least a 50% reduction. Most studies reported that at least some patients (26% to 100%) became entirely free of SE events. Although follow-up time varied significantly across studies, most showed Diacomit was effective at preventing SE in the long term.
Data from the largest study, which collected data from 131 Dravet patients who started on Diacomit before age 2, showed that 71% of patients experienced at least a 50% reduction in SE events, defined in this study as seizures lasting more than 30 minutes, after a median of two years of treatment.
Some studies suggested that the greatest effects of Diacomit were seen in patients who started treatment when they were younger.
Other reported benefits of Diacomit included a reduction in the duration of SE episodes, the ability to reduce the number of other anti-seizure medications being used, and fewer emergency department visits or hospital admissions after starting the treatment.
Three human studies, which were small case studies or case series, evaluated Diacomit’s ability to stop super-refractory SE, or SE that persists for at least 24 hours or recurs despite third-line treatment. They all involved adult patients, none of whom had Dravet. Results generally indicated that most patients experienced a quick cessation of SE with the treatment, but the researchers noted that given how few patients were involved, more studies are needed.
Data from the rodent studies indicated that Diacomit could stop SE and that it was effective even when seizures were not responsive to benzodiazepines.
Commonly reported Diacomit-related side effects in clinical studies included appetite loss, weight loss/anorexia, sleep disturbances, or mood changes including irritability or excitability, and few patients stopped treatment due to side effects, according to the authors.
Given variability in study design, small numbers of patients, and the fact that most studies were observational in nature, the researchers noted that the “conclusions drawn should be interpreted with caution.”
“The design of future studies of [Diacomit] should ideally address these limitations,” they concluded.
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