Fintepla (fenfluramine) safely lowered the frequency of drop seizures — those where part or all of the body may become limp — in patients with Lennox-Gastaut syndrome (LGS), according to data from a Phase 3 trial.
The study (NCT03355209) also showed the medication was able to lower the frequency of generalized tonic clonic seizures — characterized by abnormal electrical activity throughout the brain that usually leads to convulsions — by more than 50% in some cases.
“With … full results from our Lennox-Gastaut syndrome Phase 3 trial we are eager to continue advancing Fintepla as a potential new treatment option for additional rare epilepsies,” Bradley S. Galer, MD, chief medical officer of Zogenix, the therapy’s developer, said in a press release.
Trial findings were presented in a poster, titled “Fenfluramine for the Treatment of Patients with Lennox-Gastaut Syndrome: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial,” at the American Epilepsy Society Annual Meeting, held online Dec. 4–8.
Formerly known as ZX008, Fintepla is an oral anti-seizure medication that was recently approved in the U.S. to treat children ages 2 and older with Dravet syndrome, a drug-resistant form of epilepsy similar to LGS. The medication is currently being investigated as a potential add-on therapy to help control seizures in LGS patients.
The Phase 3 trial, also known as Study 1601, has been assessing the safety and efficacy of two daily doses of Fintepla (0.2 or 0.7 mg/kg), compared with a placebo, in reducing the frequency of seizures experienced by patients with LGS.
The study enrolled a total of 263 patients, ages 2 to 35, whose seizures tended to fail to respond to anti-epileptic medications. Before enrolling in the study, participants had already taken a median of seven different anti-seizure medications to control their seizures, without success.
Patients were allowed to continue taking their routine medications while receiving Fintepla or the placebo during an initial four-week period to determine their seizure frequency. They then entered a two-week dose titration period, where they were randomly assigned to receive increasing doses of Fintepla (or placebo) until reaching their target dose.
After that, participants entered a 12-week maintenance period, where they received fixed doses of Fintepla (or placebo). Those completing the maintenance phase of the study were also given the option to enroll in a one-year open-label extension phase to continue treatment with Fintepla.
The study’s main goal was to determine if the higher dose of Fintepla might be superior to the placebo at lowering the monthly frequency of drop seizures during the first phase of the study.
Secondary goals included a similar assessment for those receiving the lower dose of Fintepla, as well as evaluating the percentage of patients seeing their seizure frequency drop by at least 50%, considered a clinically meaningful reduction.
Top-line data previously announced by Zogenix showed the trial met its primary goal, with the higher dose of Fintepla lowering the monthly frequency of drop seizures by 26.5% compared with the placebo.
Although a reduction in drop seizure frequency was also seen among patients receiving the lower dose of the medication, these differences were not statistically significant.
The proportion of patients seeing their seizure frequency drop by at least 50% was higher among those receiving Fintepla than in those given the placebo. Likewise, the number of investigators and caregivers who rated the patients’ overall health status as “much improved” or “very much improved” on the Clinical Global Impression of Improvement test was higher in the group of patients treated with Fintepla.
The new data shows that Fintepla was particularly effective at reducing the frequency of generalized tonic clonic seizures. Compared with the placebo, the lower dose of Fintepla reduced the frequency of these seizures by 61.9%, while the higher dose lowered their frequency by 49.4%.
“Given that [generalized tonic clonic seizures] are a primary risk factor for sudden unexpected death in epilepsy, these results suggest [fenfluramine] may be an advantageous choice for LGS patients experiencing this seizure type,” the researchers wrote.
The therapy was also found to be safe and well-tolerated. The most common side effects included decreased appetite, drowsiness, fatigue, vomiting, diarrhea, irritability, seizures, and fever. None of the participants developed valvular heart disease or pulmonary arterial hypertension.
Fintepla was named an orphan drug in 2017 for the treatment of LGS by regulatory authorities in the U.S. and Europe.