Interim Results of the US Fenfluramine Oral Solution Cardiovascular Safety Registry Study
Abstract number :
1.501
Submission category :
7. Anti-seizure Medications / 7D. Drug Side Effects
Year :
2024
Submission ID :
1457
Source :
www.aesnet.org
Presentation date :
12/7/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Almasa Bass, PharmD – UCB Biosciences, Inc.
Diego Morita, MD – UCB Biosciences, Inc.
Julie Shepherd-Smith, BPharm – UCB Pharma
Rebecca Zhang-Roper, MD, PhD – UCB Pharma
Evi Tselenti, MS – UCB Pharma
Amélie Lothe, PhD – UCB Pharma S.A.
Jenna Roberts, PhD – UCB Pharma
Namita Nayak, MS – UCB Biosciences, Inc.
Rationale: In the United States (US), fenfluramine (FFA, FINTEPLA®) oral solution is FDA-approved for the treatment of seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in patients ≥2 years old. Due to cardiovascular (CV) risk, namely valvular heart disease (VHD) and pulmonary arterial hypertension (PAH), identified when FFA was used as an anorectic agent, FFA is only available in the US through a Risk Evaluation and Mitigation Strategy (REMS). This requires prescribers and pharmacies to be certified via REMS and patients to be enrolled in the program. Baseline echocardiogram (ECHO) must be obtained before starting FFA and a repeat ECHO is needed every 6 months during treatment and once 3-6 months post-FFA. As such, the FDA required a post-marketing CV safety registry study. Here we provide the interim results from that study since 2020 whose objective is to characterize the risk of potential development of REMS-defined VHD and/or REMS-defined PAH, in patients exposed to FFA in the US.
Methods: This is an ongoing prospective, observational, cohort study in the US. Data were collected via REMS and pharmacovigilance processes. If applicable, pre-REMS exposure data were obtained from clinical studies and/or early access programs. Data were included from REMS enrollment through follow-up after final FFA dose, at study end, or when patient was lost to follow-up. Data were collected from June 25, 2020, through June 24, 2024. Table 1 provides definitions for analysis sets and CV outcomes. Patient demographics, FFA daily dose, duration of exposure, and occurrence of CV adverse events and potential symptomatic or asymptomatic VHD and/or PAH will be reported for the Enrolled Set. Any case of suspected VHD or PAH are reviewed by an external adjudication committee, consisting of cardiologists with expertise in FFA and adult and pediatric cardiology. Descriptive statistics were used.
Results: As of datacut, 3563 patients have been enrolled in the REMS and received ≥1 FFA dose; 216 (6.1%) had an ECHO abnormality at baseline. Demographics are presented in Table 2. Through June 24, 2024, total duration of exposure was 5611.4 patient-years and mean±SD FFA daily dose was 0.5±0.3 mg/kg/day (17.6±9.3 mg/day). Of the 3563 patients, no patient experienced symptomatic VHD or PAH. Occurrences of REMS-defined VHD and/or REMS-defined PAH will be reported. Safety assessments and review by the adjudication committee are ongoing, including evaluation of other factors that could contribute to VHD/PAH.
Conclusions: Over the four-year evaluation period and 5611 patient-years of FFA exposure in the US, no symptomatic VHD or PAH were reported, highlighting the effectiveness of regular CV monitoring. The results of this interim report add to the current understanding of the CV safety profile of FFA and help to inform patients, caregivers, and providers of the incidence of CV adverse events.
Funding: UCB Pharma.
Anti-seizure Medications