UCB, a global biopharmaceutical company, announced that Epilepsia published findings from the final analysis of the long-term open-label extension (OLE) study evaluating the safety and effectiveness of FINTEPLA^® (fenfluramine) in patients with Dravet syndrome (DS). Results showed that FINTEPLA was generally well tolerated. The most common treatment-emergent adverse events (TEAEs) were pyrexia, nasopharyngitis and decreased appetite. The efficacy analysis showed a statistically significant and clinically meaningful sustained reduction in monthly convulsive seizure frequency (MCSF) with FINTEPLA in both children and adults with DS.²  

"Anti-seizure medications that provide long-term tolerability and effectiveness are needed for patients with DS, who often have many other medical conditions that are adversely impacted by seizure frequency and severity," said Ingrid E. Scheffer, MBBS, Ph.D., co-author of the publication and laureate professor, chair of pediatric neurology at the University of Melbourne. "This analysis, showing that FINTEPLA was generally well tolerated over the long-term and increased seizure-free days, builds on previous findings from randomized, controlled trials in adults and children with DS and provides additional evidence of the sustained tolerability and efficacy of this treatment." 

The OLE study enrolled patients with DS who had participated in one of three randomized, placebo-controlled Phase 3 trials of FINTEPLA or who were 19 to 35 years old and had not received FINTEPLA prior to study entry. The primary objective of the OLE study was to assess the long-term safety and tolerability of FINTEPLA. Efficacy endpoints evaluated the median percentage change in MCSF from Day 1 to end of study (EOS) and Day 31 to EOS compared with baseline; the proportion of patients to achieve seizure reduction thresholds; the longest convulsive seizure-free interval; and the percentage of convulsive seizure-free days in the modified intent-to-treat (mITT) population. Clinical Global Impression-Improvement (CGI-I) ratings by caregiver and investigator and changes in baseline in the Quality of Life Childhood Epilepsy (QOLCE) score were also evaluated.

Results showed that FINTEPLA was generally well tolerated with only 11 patients (2.9%) discontinuing therapy due to an adverse event. TEAEs occurring in ≥10% of patients were pyrexia, nasopharyngitis, decreased appetite, seizure, decreased blood glucose, diarrhea, abnormal echocardiogram (only physiologic regurgitation), upper respiratory tract infection, influenza, vomiting, and ear infection. No valvular heart disease or pulmonary arterial hypertension was observed in this study.

Efficacy outcomes showed a sustained reduction in MCSF with FINTEPLA in the mITT population of 324 patients, with a median change from Day 1 to EOS compared with baseline of -66.8% (p<0.001) and -67.8% (p<0.001) from Day 31 to EOS compared with baseline. FINTEPLA was effective in both patients less than six years old and those six years or older. The analysis showed that 64.2% of patients experienced a 50% or more reduction in MCSF; two patients were seizure-free throughout the OLE. From Month 1 to EOS, there was a significant 20.3% median increase in convulsive seizure-free days (p<0.0001). Caregivers rated 61.3% of patients as much/very much improved at the last visit on the CGI-I, as did 62.6% of investigators. Significant improvements from baseline were observed in several subscales of the QOLCE, including energy/fatigue, language, general health, QOL and overall QOL.

DS is a rare, severe, drug-resistant developmental and epileptic encephalopathy (DEE) that is characterized by seizure onset before the first year of life and developmental slowing or regression.^4,5 DS is often challenging to diagnose.⁶ Patients often experience multiple seizure types⁵ and effects beyond seizures, including cognitive impairment, speech impairment, sleep and gait issues, and behavioral issues, including impulsivity and hyperactivity, that can adversely impact quality of life.^5-7

"The ability to meaningfully address the complexities of Dravet, inclusive of the severe and often debilitating seizures, is critical for patients living with this rare syndrome and those who care for them," said Brad Chapman, head of U.S. epilepsy and rare syndromes at UCB. "The publication of these new long-term findings, in which patients were exposed to FINTEPLA for up to 3.5 years and experienced durable and clinically meaningful reductions in seizure frequency, emphasizes the benefit of this treatment and our commitment to helping improve outcomes for patients with DS and other rare epilepsies."