Objective:

Here we provide interim results from the FDA-required post-marketing cardiovascular (CV) safety registry study. The objective is to characterize the risk of valvular heart disease (VHD) and/or pulmonary arterial hypertension (PAH) as defined by the Risk Evaluation and Mitigation Strategy (REMS) in patients exposed to fenfluramine (FFA, FINTEPLA^®) in the US. 

Background:

VHD and PAH occurrences were reported when FFA was used as an anorectic agent; thus, FFA is only available in the US through REMS. This requires a baseline echocardiogram (ECHO) to be obtained before starting FFA, every 6 months during treatment, and once 3-6 months post-FFA.

Design/Methods:

This ongoing prospective, observational, cohort study in the US evaluates data collected via REMS and pharmacovigilance processes. This interim report captures data from June 25, 2020, through June 24, 2024. Patient demographics, FFA daily dose, duration of exposure, occurrence of CV adverse events (CVAEs) and potential symptomatic or asymptomatic VHD and/or PAH will be reported for the Enrolled Set (REMS-enrolled patients who received ≥1 dose of FFA). Cases of suspected VHD or PAH are reviewed by an external adjudication committee. Descriptive statistics are presented.

Results:

As of June 24, 2024, the Enrolled Set included 3563 patients; mean±SD age was 14.9±10.8 years and 216 (6.1%) had an ECHO abnormality at baseline. 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). No patient experienced symptomatic VHD or PAH. Occurrences of REMS-defined VHD and/or REMS-defined PAH will be reported. Assessments by the adjudication committee are ongoing.

Conclusions:

Over the 5611 patient-years of FFA exposure in the US, no symptomatic VHD or PAH was reported, highlighting the effectiveness of regular CV monitoring. The results of this interim report add to the CV safety profile of FFA and help to inform patients, caregivers, and healthcare providers of the incidence of CVAEs.