Diacomit Safe, Effective at Easing Seizures in Clinical Use Reaching Out 2 Years

Diacomit (stiripentol) is safe and effective at reducing the frequency of different types of seizures in people with Dravet syndrome when used routinely, including up to about two years, according to interim data from an ongoing study of its real-life use in Japan.

Findings from the study, “Long-term safety and effectiveness of stiripentol in patients with Dravet syndrome: Interim report of a post-marketing surveillance study in Japan,” were published in the journal Epilepsy Research.

Diacomit, an antiseizure medication marketed by Biocodex, is used as an add-on treatment to help control seizures in people with Dravet syndrome, a severe type of epilepsy that often fails to respond to anticonvulsive therapies.

The therapy uses different mechanisms to lower the abnormal brain activity underlying the onset of seizures, including that which promotes GABA signaling. GABA is the main inhibitory neurotransmitter (signaling molecule) in the brain, and is responsible for preventing excessive neuronal activity.

In Japan, Diacomit was approved in 2012 as an add-on therapy alongside Onfi (clobazam) and Depacon (sodium valproate), two antiseizure medications, to treat patients. (It is also approved in both the U.S. and the EU as an add-on Dravet therapy.)

However, due to the small number of patients in clinical trials that supported Diacomit’s approval in Japan, the Ministry of Health, Labour and Welfare (MHLW) demanded the therapy’s safety and effectiveness continued to be assessed in a post-marketing surveillance study, necessary for full approval.

This study involves patients using Diacomit as a marketed product, and is ongoing. It is expected to conclude by September 2022.

Investigators reported findings from an interim study analysis that involved up to 104 weeks (around two years) of data covering all Japanese patients who started treatment with Diacomit between its November 2012 approval and July 2019.

Patients were divided into two groups, depending on the timing of treatment start. Those given Diacomit for the first time following approval were classified as “new patients,” while those who received Diacomit in an earlier clinical trial and continuing to use it were “continuous-use patients.”

Effectiveness analyses considered patients to be responders if the number of seizures they experienced on the treatment dropped by at least 50%, compared with the number they had in the month prior to treatment initiation (a baseline measure).

From the 411 patients whose data had been added by physicians, all but two (one lost in follow-up, and one who was misdiagnosed) were included in the study’s safety and effectiveness analyses. Of these 409 people, 376 were new to Diacomit and 33 were continuous-use patients. (The misdiagnosed patient was included in treatment safety, but not efficacy, analyses.)

Patients started treatment at a median age of 7. Nearly all were also taking Depacon (99%) and Onfi (93%).

Diacomit was continuously administered over the course of 104 weeks to 305 (74.4%) patients. The remainder discontinued Diacomit  treatment at some point during follow-up largely for lack of efficacy and treatment side effects.

Safety analyses showed that 70% of new patients and 44.1% of continuous-use patients experienced side effects, with somnolence and loss of appetite being the most common in both groups. No new safety concerns associated with the use of Diacomit were identified.

Responder analyses showed that after about two years of Diacomit’s use (101–104 weeks), 43% of new patients saw the frequency of their convulsive seizures drop by more 50% compared with baseline measures.

The percentage of responders was even higher for other types of seizures, including focal impaired awareness seizures (55%) and generalized myoclonic and/or generalized atypical absence seizures (62%). Focal impaired awareness seizures are those originating in one side of the brain that cause a person to lose awareness. Generalized myoclonic and generalized atypical absence seizures affect both sides of the brain, and are accompanied either by jerky movements (myoclonic seizures) or marked by being longer lasting with slower onset and offset than typical seizures (atypical absence seizures).

Among the subset of new patients included in effectiveness analyses, physicians considered nearly half of them (45.3%) to have had a moderate or marked improvement in overall health up to the point of treatment discontinuation or study week 104.

“The present post-marketing surveillance study of all patients with DS [Dravet syndrome] who were given STP [stiripentol] in Japan found that STP did not cause any new safety concerns. Thus, STP could be administered safely, effectively, and for a long period of time for the treatment of patients with DS,” the researchers concluded.

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