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Abstracts

Descriptive Analysis of Fenfluramine Use in Adult Patients with Dravet Syndrome Enrolled in an Open-Label Extension Study

Abstract number : 3.277
Submission category : 7. Anti-seizure Medications / 7C. Cohort Studies
Year : 2023
Submission ID : 682
Source : www.aesnet.org
Presentation date : 12/4/2023 12:00:00 AM
Published date :

Authors :
First Author: Rocío Sánchez-Carpintero, MD, PhD – Clínica Universidad de Navarra

Presenting Author: Melanie Langlois, PhD – UCB

Orrin Devinsky, MD – NYU Langone Medical Center; Antonio Gil-Nagel, MD, PhD – Hospital Ruber Internacional; Tilman Polster, MD – Krankenhaus Mara - Bethel Epilepsy Centre, Bielefeld University; Diego Morita, MD – UCB Biosciences, Inc.; Mélanie Langlois, PhD – UCB Pharma, S.A.; Amélie Lothe, PhD – UCB Pharma, S.A.; Shikha Polega, PharmD – UCB, Inc.; Patrick Healy, MS – UCB, Inc.; Julia Jacobs-Le Van, MD, MSc, PD – Alberta Children’s Hospital; Ingrid Scheffer, MBBS, PhD, FRACP, FRS – The Royal Children’s Hospital

Rationale: Dravet syndrome (DS) is a rare, lifelong, treatment-resistant developmental and epileptic encephalopathy (DEE) characterized by high seizure burden, increased comorbidities, and decreased quality of life. Although onset occurs in infancy, there is long-term risk for poor outcomes if diagnosis is delayed and inadequate treatment is utilized. This analysis aims to describe the safety and efficacy of fenfluramine (FFA) in adult patients (18-35 years old) with DS who participated in the phase 3 randomized clinical trials (RCTs, NCT02682927, NCT02826863, NCT0296898) and later enrolled in the open-label extension (OLE) study, or who enrolled in the OLE study de novo.

Methods: Study design for the OLE has been previously described (Sullivan J, et al. Epilepsia 2020). Data for three patient groups enrolled in the OLE were analyzed: patients who were 18-19 yo in the RCTs, those who turned 18 yo in the OLE, and patients ≥ 18 yo who enrolled in the OLE de novo. Demographics, incidence of treatment-emergent adverse events (TEAEs), ratings on the Clinical Global Impression-Improvement (CGI-I) scale, and median percent change in monthly convulsive seizure frequency (MCSF) per 28 days were reported using descriptive statistics. Data cut-off was September 2019 and April 2020 for the RCT/OLE and de novo patients, respectively. Duration/exposure data was only available for the RCT/OLE patients with a data cut-off of October 14, 2019.

Results: Forty-one patients with DS were enrolled as adults: six were 18-19 yo in the RCTs, seven turned 18 yo in the OLE, and 28 enrolled in the OLE de novo. Twenty-one (51.2%) patients were female and mean age at screening was 22.9 y (range, 17-33). Of the 41 patients, 34 experienced ≥ 1 TEAE. There were no reports of valvular heart disease or pulmonary arterial hypertension. At last visit, 33/40 (82.5%) caregivers and 31/40 (77.5%) investigators reported improvement on CGI-I, respectively (see Figure 1). In 27/41 adult patients who had both baseline and post-baseline seizure data, the median reduction in MCSF from baseline ranged from 48.4%-83.1% over the entire OLE. The proportion of adult patients to achieve ≥ 25%, ≥ 50%, ≥ 75% and 100% reduction in MCSF from baseline is described in Figure 2; two de novo adult patients became seizure-free during their treatment with FFA. Median duration/exposure of FFA for the RCT/OLE patients was 27 months (range, 4.4-34.0).

Conclusions: In this analysis of adults with DS treated with FFA for up to three years, there were no new safety signals observed. Efficacy data and CGI-I from caregivers and investigators demonstrate clinically meaningful benefit. These data support the use of FFA as an anti-seizure medication in this subpopulation.

Funding: UCB Pharma

Anti-seizure Medications