ZX008 Yields Significant, Long-Term Seizure Reduction in Dravet Patients, Phase 3 Data Reveal

ZX008 Yields Significant, Long-Term Seizure Reduction in Dravet Patients, Phase 3 Data Reveal

Zogenix’s lead investigational compound ZX008 provided significant and long-term seizure reduction in Dravet syndrome patients, according to new clinical trial data.

The company also revealed data from multiple studies assessing the psychological and socioeconomic impact of epileptic encephalopathies, including Dravet syndrome, in the United States and Europe.

These findings were presented in multiple studies during the Annual European Congress of Epileptology (ECE) held Aug. 26-30 in Vienna, Austria.

The study, “Low-dose Fenfluramine Provides Significant and Long-term Seizure Reduction in Dravet Syndrome: Update and Follow-up of the Prospective Study,” revealed updated results of the Belgian long-term and open-label study evaluating Zogenix’s investigational therapy ZX008 to treat epileptic seizures of Dravet syndrome.

ZX008, an oral, low-dose solution of fenfluramine hydrochloride, has been used as an add-on therapy by Dravet patients in Belgium for more than two decades under a Belgian government-sanctioned compassionate use program.

Recent Phase 3 clinical studies (NCT02926898, NCT02682927 and NCT02826863) have shown that ZX008 is well-tolerated and significantly reduces the frequency of seizures in Dravet patients.

These new data regarding 15 Dravet patients confirmed the safety profile and long-term durability of ZX008’s effects. The open-label, Phase 3 study (NCT02823145) is investigating the long-term safety of ZX008 in pediatric and young adult subjects with Dravet syndrome who have successfully completed 14 weeks of treatment in one of the core studies (ZX008-1501 and ZX008-1502) and are candidates for continuous treatment for an extended period of time.

Patients were treated with ZX008 for a median duration of three years, and all participants showed a median reduction of 87% in convulsive seizure frequency during the treatment period. Also, 87% and 67% of treated participants had a 50% and 75% reduction, respectively, in convulsive seizure frequency per month compared to the beginning of the study.

“Combined with the data from our recently completed Phase 3 pivotal trials for ZX008 in Dravet syndrome, we are pleased with the durability of treatment effect that has been observed with fenfluramine in this cohort of patients who continue to experience clinically meaningful reductions in seizure frequency,” Bradley S. Galer, MD, Zogenix’s executive vice president and chief medical officer, said in a press release.

Two additional studies, “Siblings of Epileptic Encephalopathy Patients Are at Risk for Depression and Anxiety: Results From the Sibling Voices Survey,” and “Impact of Severe Rare Childhood Epilepsy on Siblings Under 18 Years of Age,” analyzed data from the Sibling Voices Survey.

This online survey was developed by Zogenix to assess the emotional impact of growing up with a sibling with severe epileptic diseases, such as Dravet syndrome and Lennox-Gastaut syndrome. It was open from July 19 to Dec. 31, 2017.

The results of the responses of 120 siblings with several ages showed they may be at a higher risk for depression and anxiety, with more than 50% reporting feelings of unhappiness, irritability, and being easily startled.

All participants reported substantial sadness and stress over their sibling’s disease, with adult siblings showing the highest degrees of worrying/stress, and 35% of them reporting to have received treatment for clinical depression.

When looking at the answers of 41 siblings under 18 years, the researchers found that feeling worried/scared when their sibling had seizures topped the siblings’ concerns.

Younger siblings (9-12 years old) struggled with less parental attention and having activities changed due to their sibling’s disease, and reported to often feel unhappy, easily scared, and grumpy.

Older siblings (13-17 years) reported being concerned about parental stress, having to help out more at home, and being embarrassed by odd behaviors, and to frequently feel easily frustrated, unhappy, and have bad dreams.

Another study “University of Washington Caregiver Benefit Scale for caregivers of children with epileptic encephalopathy,” evaluated the potential use of a 13-item University of Washington Caregiver Benefit Scale (UW-CBS) to assess the benefits of caregiving for children with epilepsy.

The results revealed these caregivers report significantly lower benefits than those of children with no special healthcare needs, but similar benefits to caregivers of children with muscular dystrophy and Down syndrome.

An additional presentation evaluating the socioeconomic impact of Dravet syndrome within the German healthcare system showed that the burden associated with seizures — reported to have happened at least one time in the prior month by 77% of those patients — was the main contributor to direct and indirect costs. The results also showed that 76% of patients required significant to extreme nursing care.

“These data suggest that the frequency and unpredictability of seizures in Dravet syndrome and other epileptic encephalopathies create a heavy burden that significantly impact the quality of life of the entire family unit,” said Lauren Schwartz, PhD, Department of Rehabilitation Medicine, University of Washington in Seattle. “Alleviating or reducing this seizure burden has the potential to not only affect the lives of patients, but also improve the quality of lives of their caregivers and siblings.”

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