A rare new drug for epilepsy in children! Fintepla (fenfluramine oral liquid) has been successfully used in the treatment of Lennox Gastaut syndrome phase III!

February 11, 2020 / BIOON / -- zogenix is a pharmaceutical company dedicated to the development of rare disease treatment drugs Recently, the company published the positive top line results of the global phase III clinical trial (study 1601) of its leading therapy fintepla (zx008, fenfluramine oral solution) in the treatment of Lennox Gastaut syndrome (LGS) LGS is a serious and difficult type of childhood epilepsy This study shows that fintepla has the potential to be an important new treatment option for LGS patients Fintepla is a kind of low-dose fenfluramine of liquid preparation, which can reduce the frequency of epileptic seizures by regulating the activity of serotonin receptor and sigma-1 receptor (see reference: fenfluramine dimentions NMDA receptor mediated seizures via its mixed activity at serotonin 5HT2A and type 1 sigma receptors) Previously, fintepla has been granted orphan drug qualification (odd) by the US Food and Drug Administration (FDA) and European Drug Administration (EMA) to treat LGS In addition, the FDA granted fintepla a breakthrough drug qualification (BTD) for the treatment of Dravet syndrome Currently, the new drug application (NDA) of fintepla for the treatment of epilepsy related to Dravet syndrome is under the priority review of FDA, and the target date of PDUFA is March 25, 2020 EMA is also reviewing the application for marketing authorization (MAA) of fintepla for Dravet syndrome LGS and Dravet syndrome are two rare and often catastrophic epilepsy in children They are characterized by early onset, multiple types of seizures, high frequency of seizures, severe impairment of intelligence, and difficult to treat Fenfluramine - molecular structure formula (image source: Wikipedia ORG) study 1601 is a multi center global LGS trial, which is divided into two parts: the first part is a double-blind, placebo-controlled study to evaluate the safety, tolerance and efficacy of fintepla's current antiepileptic program The study enrolled 263 patients aged 2-35 who were uncontrolled despite receiving one or more antiepileptic drugs (AEDs) In the study, patients were randomly divided into three groups: fintepla (0.7mg/kg/day, maximum daily dose of 26Mg; n = 87), fintepla (0.2mg/kg/day, n = 89), placebo (n = 87) The median age of the patients was 13 years old, 29% of them were ≥ 18 years old They took 1-4 kinds of AEDs, and had tried or stopped 7 kinds of other AEDs on average before The median baseline frequency of falls was 77 episodes per month After establishing a 4-week baseline frequency of falls, randomized patients titrated their doses over a 2-week titration period, followed by a 12 week fixed dose maintenance period Patients who completed part 1 were eligible for Part 2 of the clinical trial, a 12-month open label extension study to assess the long-term safety, tolerability, and efficacy of fintepla The results showed that the study reached the main end point: according to the changes of baseline examination, titration and maintenance treatment period, 0.7mg/kg/day dose of fintepla was superior to placebo in reducing the frequency of fall attacks (the median change of monthly fall attack frequency relative to the baseline: 26.5% vs 7.8%, P = 0.0012), and the data was highly statistically significant Using parametric analysis, the average frequency of falls per month in the fintepla (0.7mg / kg / day) treatment group was 26.5% lower than that in the placebo group (P = 0.0034) In addition, fintepla (0.7mg/kg/day) also showed statistically significant improvement in key secondary efficacy indicators compared with placebo, including the proportion of patients with clinically significant decrease in fall attack frequency (≥ 50%) (25.3% vs 10.3%, P = 0.0165), the proportion of patients with improved CGI-I compared with baseline (48.8% vs 33.8%, P = 0.0567), and the proportion of CGI-I patients with significant improvement from baseline (26.3% vs 6.3%, P = 0.0007) Another secondary end point of the study was that a low dose of fintepla (0.2mg/kg/day) reduced the frequency of falls by 13.2% per month between baseline and treatment, but the change was not statistically significant compared with placebo (P = 0.0915) In the study, fintepla was generally well tolerated and adverse events were consistent with those observed in the company's two previous phase III studies of Dravet syndrome Dr Kelly knupp, lead investigator of study 1601 and associate professor of Colorado children's Hospital, said: "LGS is a rare and serious epilepsy, and almost all patients have high treatment resistance and lifelong epilepsy As a result, frequent falls and injuries, as well as cognitive impairments, limit the quality of life of patients and caregivers, even under current treatment options The results observed in this placebo-controlled study suggest that fintepla has the potential to treat refractory LGS patients If approved, fintepla will become an important new treatment option for these patients and families in need " Original source: zogenix announcements positive top line results from global pivotal phase 3 trial of findepla ® for the treatment of Lennox Gastaut complex