Food and Drug Administration Grants Breakthrough Therapy Designation for ZX008 for Treatment of Dravet Syndrome
Low-dose fenfluramine (ZX008, Zogenix) is classified as an orphan drug for the treatment of two rare forms of epilepsy: Dravet syndrome and Lennox-Gastaut syndrome. Positive results from the first pivotal phase 3 trial of ZX008 by Zogenix for treatment of Dravet syndrome have led to it being first, fast-tracked, and now, granted breakthrough therapy status by the Food and Drug Administration (FDA).
Dravet syndrome is a rare (incidence 1:20,900), polymorphic epilepsy of infancy, also known as severe myoclonic epilepsy in infancy, primarily caused by a mutation in the gene coding for the sodium channel 1-alpha (SCN1A). Dravet syndrome typically begins with a febrile seizure in the first year of life and continues with more seizures and subsequent developmental delays. Dravet syndrome requires treatment of seizures and the developmental delays; however, seizures have been refractory to most known treatments to date.
FDA Breakthrough Therapy Designation is given when there is preliminary clinical evidence that an investigational drug may offer substantial improvement over existing therapies on at least one clinically significant endpoint of a clinical trial for treatment of a serious or life-threatening disease. The designation is used to classify a drug as one that will receive expedited development and review from the FDA.
According to a press release from Zogenix, the designation as a breakthrough therapy was given based on the first global phase 3 trial having met the primary efficacy endpoint and prespecified secondary efficacy endpoints. These results were announced in September 2017 and showed a 63.9% (P = .001) reduction from baseline in seizures frequency with a dose of 0.8 mg/kg per day compared to placebo. A lower dose of 0.2 mg/kg per day resulted in a 33.7% (P = .019) reduction in seizure frequency from baseline compared to placebo. The length of seizure-free intervals also increased with ZX008 treatment and an increase in seizure-free intervals. Adverse events were consistent with the know safety profile of fenfluramine.
“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,” said Gail M. Farfel, Ph.D., Chief Development Officer of Zogenix. “We look forward to working closely with the FDA as we conclude our phase 3 clinical program in Dravet syndrome, a rare and catastrophic form of childhood epilepsy.”