Standard epilepsy medications are unable to counter Dravet-associated seizures, which can cause cognitive impairment and even death. Doctors usually use anticonvulsant medications for the disease, but patient outcomes remain poor.
ZX008 is an oral formulation of fenfluramine hydrochloride, given with food.
Its potential to treat Dravet-associated seizures prompted U.S. and European regulators to grant it Orphan Drug and Fast Track status. The designations are aimed at accelerating its development and regulatory review.
The effectiveness measure that researchers used was whether ZX008 could decrease the number of patients’ monthly seizures. Researchers tested two doses of ZX008 in the trial, which consisted of a six-week observation period and 14 weeks of treatment.
The higher dose of ZX008 led to a 64 percent reduction in seizures, compared with a placebo. The lower dose led to a 34 percent drop.
Both doses led to an increase in the number of patients reporting major reductions in seizures and longer periods between seizures.
Both doses of ZX008 were safe, and patients tolerated them well, researchers said. Most of the treatment’s side effects were mild to moderate.
Although ZX008-treated patients had more adverse events than the placebo group, the number of serious side effects was the same in the two groups. There was no evidence of patients having high lung blood pressure or cardiac valvulopathy — inflamed and stiff heart valves.
The second Phase 3 trial (NCT02926898) will evaluate ZX008’s effectiveness as an add-on to a combination of standard treatment and stiripentol in children and young adults with Dravet.
Researchers will randomize patients to receive ZX008 or a placebo for 15 weeks. As with the other trial, the team will measure the treatment’s effectiveness by whether it can reduce the number of patients’ monthly seizures, compared with the placebo.
The dose that researchers select for the trial will take into account the drug interaction between ZX008 and stiripentol. With that interaction figured in, the amount of ZX008 used in the study will equate to the higher dose in the previous trial, the team said.
“We expect to announce top-line data [key results] from this study in the second quarter of this year,” Stephen J. Farr, Zogenix’s president and chief executive officer, said in a press release. “The data generated to date from the Phase 3 clinical program have further strengthened our confidence in the potential of ZX008 to become an important treatment option for the control of seizures in patients suffering from Dravet syndrome, a rare and catastrophic form of epilepsy.”