The Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for udenafil for the treatment of single ventricle heart disease (SVHD) in patients 12 years of age and older who have undergone Fontan palliation.
Udenafil is an orally administered, long acting, highly selective phosphodiesterase type 5 inhibitor (PDE5). Inhibition of PDE5 results in the relaxation of pulmonary vascular smooth muscle cells and vasodilation of the pulmonary vascular bed.
The NDA submission is supported by data from more than 200 studies completed over the last 2 decades, including the pivotal phase 3 Fontan Udenafil Exercise Longitudinal (FUEL) trial (ClinicalTrials.gov Identifier: NCT02741115), which evaluated the efficacy and safety of udenafil in 400 patients who underwent Fontan palliation. Patients were randomly assigned 1:1 to receive either udenafil 87.5mg orally twice daily or placebo. The primary endpoint was the change in exercise capacity from baseline to 26 weeks, as measured by maximal oxygen consumption at peak exercise.
Results showed that treatment with udenafil was not associated with statistically significant improvements in oxygen consumption at peak exercise compared with placebo (44 ± 245 mL/min [2.8%] vs -3.7 ± 228mL/min [-0.2%], respectively; P=.071). However, analysis at ventilatory anaerobic threshold demonstrated statistically significant improvements in submaximal exercise performance. Treatment with udenafil was associated with improvement in the myocardial performance index, but not with changes in reactive hyperemia index or serum brain-type natriuretic peptide levels.
A Prescription Drug User Fee Act (PDUFA) target date of March 26, 2022 has been assigned to the application.
- Mezzion’s New Drug Application (“NDA”) for its orphan drug udenafil for the treatment of single ventricle heart disease (“SVHD”) has been accepted for filing by the FDA. [press release]. Seoul, South Korea: Mezzion Pharma Co., Ltd.; May 25, 2021.
- Goldberg DJ, Zak V, Goldstein BH, et al. Results of the FUEL trial. American Heart Association. Published online February 25, 2020. doi: 10.1161/CIRCULATIONAHA.119.044352