Dravet Syndrome Treatment Returns Positive Results in Phase 3 Study

Results from Study 1, a randomized, double-blind phase 3 study, on low-dose fenfluramine hydrochloride (ZX008, Zogenix Inc), a treatment for Dravet syndrome, otherwise known as severe myoclonic epilepsy of infancy (SMEI), have come back positive, meeting its primary objective and proving superiority to placebo.

Study 1 examined the drug at 2 doses, 0.8 mg/kg per day and 0.2 mg/kg per day, and evaluated the epilepsy treatment’s performance in changing the frequency of seizures from a 6-week baseline observation to the 14-week treatment period (p<0.001). The findings demonstrated a significant improvement in both doses, The 0.8 mg/kg group (n=40) achieved a 63.9% average reduction in monthly seizures and an average reduction of 33.7% for the 0.2 mg/kg group (n=39), both compared with placebo.

“Dravet syndrome is a rare, but catastrophic form of epilepsy that can be devastating for patients and their families,” Joseph Sullivan, MD, director of the Pediatric Epilepsy Center in UCSF Benioff Children’s Hospital San Francisco, and principal investigator of Study 1 in the US, said in a statement. “These results are truly exciting and demonstrate, in a large multicenter controlled trial, the impressive efficacy of low-dose fenfluramine for patients with Dravet syndrome. If approved, ZX008 could play an important role in treating this devastating condition.”

The 0.8 mg/kg arm showed a median percent reduction in monthly seizure frequency of 72.4% compared to 17.4% with placebo. The drug was generally well tolerated, with the adverse events occurring remaining consistent with fenfluramine’s known safety profile.

A patient population of 119 was randomized to each of the 3 arms a 1:1:1 ratio. Patients were titrated to their assigned dose and then remained at the fixed dose for 12 weeks. The secondary endpoint of the proportion of patients with a 50% reduction in seizures was seen by 70% of the 0.8 mg/kg dose group and by 41% of the 0.2 mg/kg dose group, compared to 7.5% on placebo.

The 0.8 mg/kg cohort observed the longest seizure-free period at 20.5 days (p<0.001), while the 0.2 mg/kg group saw a 14-day period (p=0.011) and 9 days with placebo. This is especially heartening, as improving the quality of life for epilepsy remains one of the biggest unmet needs, according to Jerry J Shih, MD, the director of the epilepsy center and a profesor of neurosciences at UC San Diego Health.

"One of the biggest unmet needs in the field of epilepsy is how do we improve quality of life in patients who continue to have seizures? A lot of energies have been focused on trying to eliminate seizures to make people seizure-free, and absolutely that's our primary goal," Shih told MD Magazine. "But for patients who are not seizure-free and who have undergone all of the appropriate studies — have tried a number of medications, may have gone through some surgical evaluation and procedures and are still not seizure-free – I think one of the challenges is how we as a society can come up with better ways of elevating their quality of care, our quality of life."

Zogenix is expecting top-line results from Study 1504, which is nearing full enrollment its second phase 3 study, in the first half of 2018.