The U.S. Food and Drug Administration has granted breakthrough therapy designation to ZX008 to treat seizures associated with Dravet syndrome.
This new status adds to the orphan drug and fast track designations previously granted by the FDA and the European Medicines Agency (EMA) and is intended to support the clinical development of ZX008 and expedite regulatory review for its approval to treat patients with this life-threatening disease.
ZX008 is a low-dose formulation of fenfluramine that is being developed by Zogenix. The compound can stimulate the release and activity of several neuroactive signaling molecules, including serotonin, which is known to have an antiepileptic effect.
Data from two parallel Phase 3 clinical trials, referred to by Zogenix as “Study 1,” (NCT02682927, NCT02826863) in children and young adults with Dravet syndrome have demonstrated the potential of this investigative therapy.
The researchers analyzed merged clinical data of 119 participants whose seizures were not controlled completely with their available therapy regimen. Patients were randomized to receive ZX008 0.2 or 0.8 mg/kg per day, or placebo for a total of 14 weeks.
Treatment with ZX008 significantly reduced the number of convulsive seizures. The group treated with the higher dose experienced a reduction of mean monthly convulsive seizures of 63.9% compared to placebo, and those treated with a lower dose had a reduction of 33.7%.
Approximately 26.2% of the participants who received ZX008 did not have any seizures during the trial period and 15.2% had only one seizure. In contrast, none of the placebo-treated patients achieved such a low frequency of seizures.
These results were presented at the 71st Annual Meeting of the American Epilepsy Society held in December 2017 in Washington, D.C. The presentation was titled “ZX008 (Fenfluramine HCl Oral Solution) in Dravet Syndrome: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial.”
“We are very pleased that the FDA has granted Breakthrough Therapy Designation based on the efficacy and safety results from Study 1 reported in fall of 2017,” Gail M. Farfel, PhD, chief development officer of Zogenix, said in a press release. “We look forward to working closely with the FDA as we conclude our Phase 3 clinical program in Dravet syndrome.”
The trial, expected to finish in the summer of 2018, is going to evaluate the safety and effectiveness of twice-daily oral administration of ZX008, in a maximum dose of 20 mg per day, compared to placebo when added to those approved antiepileptic therapies for 18 weeks. Similar to previous studies, the primary outcome measure is change in frequency of convulsive seizure.