Fenfluramine, Antiseizure Medication With Durable Profound Seizure Reduction to Be Resubmitted to FDA This Month
In clinical trials, treatment with low dose fenfluramine (Fintepla; Zogenix, Emeryville, CA) has resulted in large consistent durable reductions in seizure frequency for individuals with Dravet’s syndrome (DS). In 2 pivotal clinical trials, children age 2 to 18 years, who were treated with fenfluramine had a 63% or 54% reduction in monthly convulsive seizure frequency from baseline compared with those treated with placebo.
In responder analysis, approximately half to two-thirds of those treated with fenfluramine had a profound (>75% reduction in seizure frequency) or clinically meaningful (>50% reduction in seizure frequency) response, respectively. Relief from seizures has been maintained at the same levels in 21 months of treatment in open-label extension trials for over 200 participants. At 21 months, approximately 41% of participants treated with fenfluramine continue to have a profound reduction in seizure frequency.
Arnold Gammaitoni, PharmD, vice president of Global Medical and Scientific Affairs of Zogenix said, “We are especially pleased with the magnitude, durability, and consistency of seizure frequency reduction seen with Fintepla. The condition being studied are highly refractory to current medical treatment, creating a high level of unmet medical need. We are hopeful that we will soon bring this drug to the individuals who need it.”
As reported at the 2018 American Epilepsy Society meeting, a higher proportion of children and young adults with DS treated with fenfluramine for 14 weeks had improvements in behavior regulation index (BRI) scores (25% vs 5%, P = .01) and emotional regulation index scores (29% vs 5%; P = .005) compared with those given placebo. The ability to plan and organize was also improved in those treated with fenfluramine. These children and young adults continue to be followed, and longer-term cognitive effects of fenfluramine treatment will be presented at the American Epilepsy Society meeting in December 2019.
Brad Galer, MD, chief medical officer of Zogenix, said “We’ve been working extremely hard in resubmitting our NDA for Fintepla, which we will resubmit to the Food and Drug Administration and at the end of the month. We are 100% laser focused on getting Fintepla to the individuals who need it, both for Dravet’s syndrome and hopefully for LGS, for which clinical trials are ongoing with data readout expected in the first quarter 2020.”
No participants in clinical trials (pivotal or open label extensions) of low dose fenfluramine have developed valvulopathy or pulmonary arterial hypertension, with some subjects now on their third year of treatment; this is notable because fenfluramine when used at higher doses, and most often in combination with phentermine to treat adult obesity was previously withdrawn from the market when these adverse events occurred. Adverse events in the study of Fintepla have included sedation, loss of appetite, and nausea, which tend to resolve with continued treatment.