Zogenix reported that its lead experimental therapy Fintepla met both its primary and secondary endpoints in reducing the frequency of drop seizures in a global phase 3 study in patients with Lennox-Gastaut syndrome, a severe and treatment-resistant childhood-onset epilepsy.
Shares of Zogenix lost a third of their value, however, as investors were not impressed by the magnitude of the improvements in patients because they were not significantly better than that achieved in studies of GW Pharmaceuticals’ cannabinoid-based drug Epidiolex, and because they expect Fintepla (fenfluramine) to be more expensive and therefore likely used as a second-line treatment.
Epidiolex is already approved in the United States and Europe as a treatment for both Lennox-Gastaut and Dravet syndromes.
Lennox-Gastaut syndrome (LGS) is a rare and devastating form of childhood-onset epilepsy characterized by many different seizure types, which are hard to control and often don’t respond to currently available seizure medications. The intellectual and behavioral problems associated with LGS, as well as around-the-clock care requirements, add to the complexity of life with this disease.
“LGS is a rare and severe form of epilepsy where nearly all patients have highly treatment resistant and lifelong seizures. As a result, the frequent falls and injuries, and also the cognitive impairment, limit the quality of life for patients and caregivers, even with current treatment options,” said Associate Professor Kelly Knupp, of Children’s Hospital Colorado and principal investigator of the study. “The results observed in this placebo-controlled study are indicative of the potential of fenfluramine to treat patients with refractory LGS.”
The two-part phase 3 multicenter, global trial enrolled 263 patients between the ages of 2 and 35 years whose seizures were currently uncontrolled while on one or more anti-epileptic drugs. The median baseline drop seizure frequency across the study groups was 77 seizures per month. Patients were randomized into three groups: high dosage, low dosage, and placebo. After establishing baseline seizure frequency for 4 weeks, randomized patients were titrated to their dose over a 2-week titration period, followed by a 12-week fixed dose maintenance period. Patients who completed part 1 were eligible to enter part 2 of the clinical trial, an ongoing 12-month open-label extension study to evaluate the long-term safety, tolerability and effectiveness of Fintepla.
The trial met its primary objective of demonstrating that at its high dose, Fintepla reduced the frequency of drop seizures by 26.5 percent compared to a 7.8 percent reduction in the placebo group. Patients taking the high dose also demonstrated statistically significant improvements versus placebo in key secondary efficacy measures, including the proportion of patients with a clinically meaningful reduction of greater than 50 percent drop in seizure frequency. Fintepla was generally well-tolerated, with the adverse events consistent with those observed in the Zogenix’ two prior phase 3 studies in Dravet syndrome.
“We are pleased with the top-line efficacy and safety results from Study 1601, which highlight Fintepla’s potential to be an important new treatment option for one of the most difficult to treat rare epilepsies,” said Stephen Farr, president and CEO of Zogenix.
Fintepla has U.S. and E.U. orphan drug designation as a treatment for LGS. It is also currently under priority review by the U.S. Food and Drug Administration for marketing approval as a treatment for seizures associated with Dravet syndrome, with a March 25 decision date. It is also under review by the European Medicines Agency for the same indication.
Photo: Stephen Farr, president and CEO of Zogenix