Neuro News Roundup: Dravet Syndrome Awareness Day


In honor of Dravet Syndrome Awareness Day, held June 23, 2023, get caught up on some of the latest news in Dravet syndrome as the NeurologyLive® team shares some of our data updates.

In recent months, the NeurologyLive® team has been covering the news on the latest updates in the clinical care of individuals with neuromuscular disorders, multiple sclerosis, movement disorders, sleep disorders, and more.

For Dravet Syndrome Awareness Day — June 23, 2023 —the team has culminated some of the biggest pieces of news to offer updates on new developments in literature on Dravet syndrome to spread awareness on the prevention and treatment of the epilepsy condition.

Click here for more coverage of the latest epilepsy news from NeurologyLive®.

Latest Literature

DEA Rules Fenfluramine No Longer a Controlled Substance

Originally marked as a Schedule IV controlled substance, the DEA has published its final ruling on fenfluramine (Fintepla; UCB Pharma) stating that the oral medication is no longer subject to the Controlled Substances Act (CSA). Following receipt of this DEA rule, UCB has filed a labeling supplement with the FDA to remove Schedule IV designation from the medication.1

Fenfluramine, an antiseizure medication, originally received FDA-approval as a therapy for Dravet syndrome in patients aged 2 years and older in 2020, and later for the treatment of Lennox-Gastuat syndrome in March 2022. With the new ruling, most prescribers will be able to write a prescription for a full year’s supply versus the current limitation of 6 months. Prescribers will also now have the option to send a prescription to pharmacies electronically.

Schedule IV drugs, substances, or chemicals are defined as drugs with a low potential for abuse and a low risk of dependence. Other examples of these drugs include Xanax, Soma, Darvon, Darvocet, Valium, Ativan, Talwin, Ambien, and Tramadol. In its labeling, fenfluramine has been noted to cause some serious adverse events, including valvular heart disease and pulmonary arterial hypertension. Echocardiograms are taken prior to fenfluramine initiation, again every 6 months during treatment, and 1 time 3-6 months after the last dose of fenfluramine.

The therapy also has boxed labeling about potential decreased appetite and weight, as well as increased sleepiness, sedation, and lack of energy. Like all other antiepileptic drugs, fenfluramine may cause suicidal thoughts or actions, although rare. Fenfluramine should not be prescribed to those who may be allergic to any of the ingredients of the therapy, and for those who are taking or have stopped taking monoamine oxidase inhibitors in the previous 14 days as this might cause serotonin syndrome.

DEA Rules Fenfluramine No Longer a Controlled Substance

Seizure-Free Days and Duration Intervals Increased With Fenfluramine in Dravet Syndrome

News from a recent post-hoc pooled analysis of two clinical trials (NCT02682927, NCT02826863) showed an increase in seizure-free days and increased duration of seizure-free intervals with antiseizure medication, fenfluramine (Fintepla; UCB Pharma), in patients with Dravet syndrome (DS).2 These findings suggest that there might be a dose-response to the treatment and that the quality of life for both caregivers and patients may improve.

All told, there was a significantly higher probability of not reaching the pre-randomization seizure count in both fenfluramine groups, fenfluramine 0.7 mg/kg/day (62.3%) and fenfluramine 0.2 mg/kg/day (35.3%), in comparison with the placebo group (9.1%)(both fenfluramine groups, P <.001).

The investigators observed that during the 14-week titration and maintenance period, fenfluramine increased the probability of failing in the count for the pre-randomization convulsive seizures. The study was conducted as a time-to-event (TTE) analysis, an alternative to routinely used clinical trial endpoints, as a way to provide data on changes in seizure frequency. TTE was defined as the time required during the 14-week combined titration-maintenance period to experience the same number of convulsive seizures as experienced during the baseline period (Kaplan-Meier log-rank test). The participants were patients with DS, 2 to 18 years of age, with no pulmonary hypertension or cardiovascular or cerebrovascular disease history.

At baseline, the average number of convulsive seizures ranged from 22.0 to 28.5 and the average number of seizure-free days per 28 days ranged from 16.3 to 19.3 days. The seizure free days per 28 days with treatment were analyzed by ANCOVA, using age as factors. The log baseline seizure-free days per 28 days was a covariate and a response. The Wilcoxon rank sum test analyzed the longest convulsive seizure-free interval.

Seizure-Free Days and Duration Intervals Increased With Fenfluramine in Dravet Syndrome

Strong Communication on Seizure Management Leads to Improved Care in Dravet Syndrome

In a recent qualitative study, findings suggested that a strong foundation of trust between clinicians and the caregivers of patients with Dravet syndrome (DS) is a critical component for successful treatment decision in this patient population.3 This analysis provided evidence that most effective way to combat the complexity of treatment for the disease is communication.

In the study, investigators observed high levels of anxiety in all caregivers of patients with DS that was linked to the treatment decisions for these patients. They concluded that having trust in a healthcare provider is important for the caregivers, allowing them to feel more confident to discuss their concerns, thus potentially may improving engagement with care priorities. Although, building a foundation of trust with a clinician for caregivers may be a challenge especially after poor past experiences.

The analysis showed that besides the challenges with caring for DS, priorities for the management of seizures following diagnosis need to be considered with a caregiver’s focus. The study included 43 families spanning across 5 European countries. For patients with DS, the age ranged from 15 months of age for children up to 23 years of age for young adults. The severity of DS among those included ranged from mild to severe. There were telephone and video conferences interviews performed by the investigators until no new additional information was provided. This study’s interpretative phenomenological analysis was ultimately applied to analyze the data and to make observations on emerging themes.

Strong Communication on Seizure Management Leads to Improved Cartrong Communication on Seizure Management Leads to Improved Care in Dravet Syndrome

Transition to Adult Care Is Inconsistent for Patients With Dravet Syndrome, Survey Suggests

The findings of an electronic survey of adult individuals with Dravet syndrome (DS) and their caregivers suggest that a large number of these patients do not undergo a transition of care from pediatric physicians to adult physicians, highlighting a possible detriment to the optimal care of these individuals.4

Ultimately, of the 46 survey responses that were included in the analysis, almost two-thirds (n = 29; 63%) of the adults with DS did not undergo the transition to adult care, and most were still being followed by their pediatric physicians (n = 20; 71%). Other reasons for a lack of transition of care included discharge from the pediatric clinic (n = 5; 18%), diagnosis by an adult neurologist or epileptologists (n = 2; 7.1%), or other (n = 1; 3.6%).

Of the individuals who had undergone, or were undergoing, the transition of care (n = 17; 37%), the average age of patients when the conversations about transition began with the pediatric care team was 19 years (range, 16-27). These patients first saw an adult neurology physician at an average age of 21.6 years (range, 18-28). Of those who transitioned care, 29% (n = 5) were being seen by both their pediatric and adult provider simultaneously, for a range of 4 to 24 months, with a single respondent still being seen by both at the time of the survey.

All told, more than half of the 17 surveyed caregivers who underwent a transition of care noted that these challenges were either never or rarely addressed. The only item that was indicated as something that always or often occurred was the addressing of patients’ self-advocacy capabilities—still only reported by fewer than half of the caregivers.

Transition to Adult Care Is Inconsistent for Patients With Dravet Syndrome, Survey Suggests

New Prospective Data on Patients With Dravet Syndrome Inform Outcome Measurements in Trials

Data from the BUTTERFLY study suggest that over the course of 12 months, patients with Dravet syndrome (DS) who were being treated with antiseizure medications (ASMs) experienced small improvements in receptive communication, with most deemed either unchanged or slightly improved on measurements of cognition. The study investigators noted that these data—including the lack of significant changes—will help inform outcome measurements for future trials in DS.5

On the Vineland Adaptive Behavior Scales-III (VABS-III), the least squares (LS) mean change from baseline to 12 months was 5.49 (95% CI, 0.56-10.41; P = .030) for receptive communication. The LS mean change for expressive communication was 2.37 (95% CI, –0.10 to 4.85; P = .060), and for interpersonal relationships was 2.99 (95% CI, –1.22 to 7.20; P = .16), with gross and fine motor scores changing by 1.90 points (95% CI, –3.24 to 7.05 P = .45) and 3.59 points (95% CI, –1.93 to 9.11; P = .19), respectively.

On the cohort's Bayley Scales of Infant Development-III (BSID-III) scores, the LS mean change in cognitive scores was –1.08 (95% CI, –3.53 to 1.37; P = .37). The LS mean change on BSID-III receptive communication and expressive communication scores were 3.68 (95% CI, 0.48-6.89; P = .027) and 3.23 (95% CI, –1.66 to 8.11; P = .18), respectively.

BUTTERFLY, conducted by Stoke Therapeutics, is an observational study aimed at collecting information about the mental development, behavior, movement, communication skills, seizure frequency, and sleep patterns of young people with DS.1,2 The primary objective is to assess neurodevelopmental change from baseline to 24 months, with secondary outcomes of the number of countable convulsive seizures per 4 weeks prior to visits and the change from baseline in clinical status, quality of life, and executive function.

New Prospective Data on Patients With Dravet Syndrome Inform Outcome Measurements in Trials
1. UCB announces Fintepla (fenfluramine) oral solution is now descheduled and is no longer listed as a controlled substance. News release. April 17, 2023. Accessed June 21, 2023.
2. Sullivan J, Specchio N, Devinsky O, et al. Time-to-Event Analysis to Measure Treatment of Fenfluramine Therapy: Pooled Analysis of Two Phase 3 Studies in Dravet Syndrome. Presented at: AES Annual Meeting; December 2-6, 2022; Nashville, TN, and virtual. Poster.
3. Luker J, Fisher K. Balancing seizure management with broader needs in the Dravet Syndrome patient: a qualitative study of the lived experience of patients and families. Presented at: AES Annual Meeting; December 2-6, 2022; Nashville, TN, and virtual. Late Breaking Poster 467.
4. Nascimento FA, Yap S, Sheikh IS, Hood V, Meskis M, EA Thiele. Epilepsy transition of care in Dravet syndrome. Presented at: AES Annual Meeting; December 2-6, 2022; Nashville, TN, and virtual.
5. Sullivan J, Wirrell E, Knupp KG, et al. Twelve-month analysis of BUTTERFLY: An observational study to investigate cognition and other non-seizure comorbidities in children and adolescents with Dravet syndrome (DS). Presented at: AES Annual Meeting; December 2-6, 2022; Nashville, TN, and virtual.
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