Fintepla Improves Behavioral and Emotional Control in Dravet Patients, Analysis of Phase 3 Trial Shows
Zogenix‘s investigational compound Fintepla (fenfluramine HCl oral solution) improves behavioral and emotional control in children and young adults with Dravet syndrome, according to recent data presented at the 72nd American Epilepsy Society Annual Meeting in New Orleans.
These findings were based on a post-hoc analysis performed on patients who participated in Zogenix’s Study 1 for Fintepla, also known as ZX008.
The company also presented data on findings from two additional analyses examining the impact of Dravet syndrome and other epileptic diseases on patients’ siblings and parents.
Study 1 was a prospective analysis of a randomized, double-blind, placebo-controlled Phase 3 clinical trial (NCT02682927); a second identical Phase 3 study (NCT02826863) is underway. These trials were designed to assess the efficacy and safety of Fintepla at a dose of 0.2 mg/kg/day and 0.8 mg/kg/day in children and young adults with Dravet syndrome over a period of 14 weeks compared with a placebo.
The study, “Improved Everyday Executive Function With Fintepla® (Fenfluramine HCl Oral Solution): Results From a Phase 3 Study in Children and Young Adults With Dravet Syndrome,” assessed the impact of Fintepla on caregiver-reported everyday executive function of children with Dravet syndrome. A total of 77 patients out of the 119 originally enrolled in Study 1 were examined using the Behavior Rating Inventory of Executive Function (BRIEF) scale.
This scale was specifically designed to assess everyday executive function of Dravet patients between 5 and 18 years old based on reports from their parents and caregivers. The post-hoc analysis was based on an updated, more stable, and sensitive version of the scale, called BRIEF2, which was applied to patients at the start of the study and after 14 weeks of treatment.
After 14 weeks of treatment with Fintepla, patients achieved clinically meaningful improvements in behavior, emotion, and cognitive regulation compared with those on placebo. However, no significant differences were found between patients treated with different doses of Fintepla.
“The clinically meaningful impact of Fintepla on behavioral and emotional regulation is encouraging, as these are considered the ‘building blocks’ necessary for higher-level cognitive function,” Gerard A. Gioia, PhD, division chief of neuropsychology at the Children’s National Health System in Maryland, said in a press release. Gioia is also the co-author of the BRIEF and BRIEF2 scales.
“These responses to [Fintepla] will continue to be examined in the long-term extension study (NCT02823145) to determine if everyday executive function continues to improve with longer-term treatment with [Fintepla],” the researchers wrote.
Two additional posters, “Assessing Quality of Life in Siblings of Children With Severe Epileptic Encephalopathies: A Comparative Analysis of Sibling Self-Reports and Parental Perception of Sibling Experiences” and “Psychosocial Concerns of Growing Up With a Sibling With a Severe Epileptic Encephalopathy: Results From the Sibling Voices Survey Identify Potential Targets for Psychosocial Assessment,” included new analyses of data from the Sibling Voices Survey.
This online survey was created by Zogenix to examine the emotional impact of growing up with a sibling with severe forms of epileptic encephalopathies (EE), such as Dravet syndrome and Lennox-Gastaut syndrome. Between July 19 and Dec. 31, 2017, the survey gathered responses from 128 parents, representing 115 patients, and 120 siblings, representing 107 patients with an EE.
The first analysis assessed quality of life in siblings of children with EEs and compared parental perception and sibling reports on the psychosocial impact of growing up with a sibling with an EE.
Findings revealed substantial differences between parental perception and sibling reports on mood symptoms, degree of sadness, anger, worry/fear, and stress, and a nearly twofold difference in responses regarding lack of parental attention and comfort level in talking with others about the sibling’s diagnosis.
The second analysis assessed the psychosocial concerns of growing up with a sibling with severe EE from the perspective of their brothers and sisters. Young siblings (13-17 years old) described feelings of guilt, resentment, and jealousy toward their sibling. Conversely, adult siblings (older than 18) reported feeling overly responsible for the well-being of their affected sibling.
Researchers believe that these results “highlight the need for increased awareness and ongoing assessment of the potential need to support siblings of patients with an EE,” and that clinicians “should discuss the potential for sibling depressed mood and anxiety with parents.”
Future research should identify “specific interventions to improve care and reduce the emotional burdens/stress on siblings,” they said.