공시 • May 03
UCB Announces Jama Neurology Publishes Phase 3 Study Results on the Efficacy and Safety of Fintepla® (Fenfluramine) Oral Solution in Lennox-Gastaut Syndrome
UCB announced the publication in JAMA Neurology of its multi-center, double-blind, placebo-controlled, parallel-group, randomized Phase 3 trial demonstrating that FINTEPLA 0.7 mg/kg/day, when added to a patient's current anti-epileptic treatment regimen for seizures associated with LGS, is effective in reducing the frequency of drop seizures.1 Drop seizures cause a person to suddenly lose muscle tone, become limp, and fall to the ground, with a high likelihood of injury.6 Within the study, drop seizures were further defined as GTC, secondary GTC [focal to bilateral tonic clonic], tonic, atonic, or tonic and atonic. LGS is a severe childhood-onset developmental and epileptic encephalopathy characterized by drug-resistant seizures with high morbidity2 as well as serious impairment of neurodevelopmental, cognitive and motor functions. LGS has far-reaching effects beyond seizures, including issues with communication, psychiatric symptoms, sleep, behavioral challenges and mobility.7 LGS affects 30,000-50,000 patients in the U.S. The trial met its primary efficacy endpoint. Patients taking FINTEPLA 0.7 mg/kg/day experienced an estimated mean difference in the reduction of drop seizure frequency by 19.9% from placebo (P=.001). The median percent reduction in the frequency of drop seizures in the 0.7 mg/kg/day group was 26.5%, compared with 14.2% in the 0.2 mg/kg/day group, and 7.6% in patients taking placebo (P=.09). In key secondary outcomes, the trial demonstrated that a greater proportion of patients taking FINTEPLA experienced a 50% or greater reduction in drop seizure frequency, compared with patients in the placebo group. The study also included a seizure-type subgroup analyses that demonstrated that FINTEPLA 0.7 mg/kg/day was highly effective in reducing the frequency of GTCs in nearly 50% of patients. During the maintenance and titration period, patients experienced a decrease in frequency of 45.7% in the FINTEPLA 0.7 mg/kg/day group, a decrease in frequency of 58.2% in the 0.2 mg/kg/day FINTEPLA group, compared with an increase in frequency of 3.7% in the placebo group (P=.001 and P<.001 respectively). The percentage reduction in tonic or atonic seizure frequency was 46.7% in the FINTEPLA 0.7 mg/kg/day group, compared with 6.8% in the placebo group (P=.046). The reason these data are compelling is because GTCs are commonly observed in patients with LGS.9 Moreover, GTCs may result in bodily injury. Sudden unexpected death in epilepsy (SUDEP) is a major concern for people living with LGS, and patients with a history of GTCs have an estimated 10-fold greater risk of SUDEP. FINTEPLA was generally well-tolerated in this study. The most common treatment-emergent adverse events included decreased appetite, somnolence, and fatigue. The FINTEPLA safety database includes long-term cardiovascular safety data for patients treated for up to 3 years in Dravet syndrome (DS) and LGS. Site investigators and caregivers also rated patients as significantly much or very much improved on the Clinical Global Impression of Improvement (CGI-I) scale (investigators 26% vs. 20% vs. 6% and caregivers 34% vs. 27% vs. 5% for 0.7 mg/kg vs. 0.2 mg/kg vs. placebo, respectively). FINTEPLA was approved by the U.S. FDA for the treatment of LGS in patients 2 years and older in March 2022 and was also approved for the treatment of DS in patients 2 years and older in June 2020. UCB acquired Zogenix Inc. and FINTEPLA on March 7, 2022. The acquisition is consistent with UCB's sustainable patient value strategy and continued commitment to providing patient value to all people living with epilepsy, with an increasing focus on creating value and new solutions that address the unmet needs of people with certain specialized or rare types of epilepsy, where few or no options exist. The multi-center, double-blind, placebo-controlled, parallel-group, randomized Phase 3 clinical trial was conducted from 27 November 2017 to 25 October 2019, and had a 20-week trial duration. Patients were enrolled at 65 study sites in North America, Europe, and Australia. A total of 263 patients were randomly assigned to receive either FINTEPLA 0.7 mg/kg/day (n=87) or FINTEPLA 0.2 mg/kg/day (n=89) or placebo (n=87). After titration (2-week period), patients were maintained on their randomized dose for 12 additional weeks. The median age was 13 years of age. Children and adults, aged 2 to 35 years, with a confirmed LGS diagnosis who were using stable anti-seizure medication (ASM) regimens (=1 and =4 concomitant ASMs) were eligible for enrollment if these criteria were met: onset of seizures at age 11 years or younger; multiple seizure types, including tonic and tonic or atonic seizures; stable 4-week seizure baseline with 2 of more drop seizures per week of GTC, or secondary GTC (i.e., focal to bilateral tonic-clonic seizures), tonic, atonic, or tonic or atonic seizure; abnormal cognitive development; and medical history showing electroencephalogram evidence of abnormal background activity with slow spike-and-wave pattern (<2.5Hz). Key exclusion criteria were degenerative neurological disease, history of hemiclonic seizures in the first year of life, only drop seizure clusters, previous or current exclusionary cardiovascular or cardiopulmonary abnormality or concomitant cannabidiol use (not FDA approved at time of study). This study was funded by Zogenix Inc., now part of UCB.