Udenafil

SEOUL, South Korea, Aug. 12, 2025 /PRNewswire/ -- A newly published post-hoc analysis of the landmark FUEL (Fontan Udenafil Exercise Longitudinal) Trial demonstrates that udenafil, a PDE5 inhibitor, significantly improves peak oxygen consumption (peak VO₂) in adolescents with single ventricle congenital heart disease (SV-CHD) who have undergone the Fontan procedure and have reduced exercise capacity. Published in the Journal of the American Heart Association: "Revisiting the Effect of Udenafil on Exercise Performance in Patients With Fontan Circulation: Results of a Post Hoc Analysis of the FUEL Trial" The original multinational, randomized, placebo-controlled Phase 3 FUEL trial demonstrated statistically significant improvements in key secondary endpoints – such as VO₂ at ventilatory anaerobic threshold (VAT) and myocardial performance index (MPI) – but narrowly missed statistical significance for the primary endpoint of peak VO₂ in the overall population. Recognition of a high performing "Super Fontan" subgroup prompted further analysis stratifying participants by baseline peak VO₂ (<80% vs. ≥80% of predicted) to assess whether initial exercise capacity influenced treatment response. Key findings from the post-hoc analysis: In the 302 patients with baseline peak VO₂ <80% predicted (80% of the evaluable cohort), udenafil significantly improved peak VO₂ compared to placebo (p=0.021). Significant improvements were also observed in VO₂ at VAT (p=0.023), work at VAT (p=0.032), and MPI (p=0.007). A significant interaction between baseline exercise capacity and treatment effect for peak VO₂ (p=0.036) suggests that including high-functioning patients, whose physiologic ceiling may limit measurable gains, could have masked the full treatment effect in the original trial. "These results provide a possible physiologic explanation for the outcomes of the FUEL trial and support further investigation of udenafil in Fontan patients with reduced exercise capacity," said Dr. David Goldberg, lead author and pediatric cardiologist at Children's Hospital of Philadelphia. "This analysis highlights the need for a confirmatory clinical trial targeted to the large majority of Fontan patients who are most likely to demonstrate benefit using peak VO2 as the primary endpoint." "Importantly, the absence of a detectable change in peak VO₂ among higher-functioning Fontan patients may reflect– what may be termed a 'ceiling effect' – rather than a lack of therapeutic response," added Dr. Bryan H. Goldstein, senior author and Director of the Cardiac Catheterization Laboratory at UPMC Children's Hospital of Pittsburgh. "These patients still achieve meaningful improvements in submaximal exercise measures such as VO₂ at VAT and MPI. Moreover, as these younger, high-performing individuals age and are further exposed to ongoing Fontan circulatory stresses, their exercise capacity with decline and therefore, the need for targeted pharmacotherapy will likely increase." The findings highlight the importance of selecting appropriate endpoints and stratifying populations in rare disease trials. Informed by FUEL, the ongoing confirmatory phase 3 FUEL-2 trial focuses on Fontan patients with reduced baseline exercise capacity – those in whom changes in peak VO₂ are most reliably measurable. "This focused design increases the likelihood of demonstrating efficacy on the primary endpoint, while still capturing udenafil's broader therapeutic potential," said Dr. Rahul Rathod, Global Principal Investigator for FUEL-2 and Director of the Single Ventricle Program at Boston Children's Hospital. "Given the strong link between peak VO₂ and long-term outcomes in Fontan patients, a +1.13 mL/kg/min improvement over six months is clinically meaningful and may influence disease progression." The FUEL trial was supported by the National Heart, Lung, and Blood Institute (NHLBI) and Mezzion Pharma Co., Ltd., the regulatory sponsor of udenafil development for Fontan patients. About Mezzion Mezzion Pharma Co., Ltd. is a biopharmaceutical company developing therapies for rare and orphan diseases. Udenafil is currently being evaluated in the Phase 3 FUEL-2 trial for improving exercise performance in adolescents and young adults with Fontan circulation. For more information, please visit and . Media Contacts: John Presser, Chief Business Officer – [email protected] Sung-Il Noh, Chief Financial Officer – [email protected] SOURCE Mezzion Pharmaceuticals, Inc WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

SEOUL, South Korea, July 31, 2025 /PRNewswire/ -- Mezzion Pharmaceuticals, Inc. (Mezzion) announced that its confirmatory Phase 3 FUEL-2 study evaluating JURVIGO® (udenafil)1 in adolescents and young adults with Fontan circulation has surpassed a key enrollment milestone randomizing approximately 50% of the planned 400+ participants. Continue Reading “FUEL-2 is aiming to bring hope to a resilient and underserved community.” FUEL-2 is the largest randomized clinical trial ever conducted for the Fontan population, a group of patients born with single ventricle congenital heart disease who require a series of surgeries culminating in the Fontan procedure. This population remains at high risk for heart failure, organ dysfunction, and early mortality, with no FDA-approved pharmacologic therapies available today. "The Fontan journey is long, complex, and often isolating," said Dr. Rahul Rathod, Global Principal Investigator for FUEL-2 and Director of the Single Ventricle Program at Boston Children's Hospital. "With FUEL-2, we're doing more than just advancing a treatment – we're building hope, community, and scientific clarity around a disease that has gone too long without answers." Udenafil, a highly selective and long-acting PDE5 inhibitor, has demonstrated its clinical benefit in Fontan patients with reduced functional capacity (peak VO₂ < 80% of predicted). In the original FUEL trial, this subgroup experienced the most pronounced improvements, particularly in submaximal exercise measures such as ventilatory efficiency and anaerobic threshold – indicators closely tied to functional status in daily life. These findings, combined with FDA-aligned guidance and a growing body of published evidence, informed the focused enrollment criteria for FUEL-2, which is evaluating udenafil exclusively in this higher-risk population. Udenafil has been shown to be safe and well tolerated across more than five years of cumulative exposure, including long-term use in a diverse group of adolescents and young adults from the FUEL trial's open-label extension. In FUEL-2, the primary efficacy endpoint is the change in peak VO2 (mL/kg/min) following 26 weeks of treatment. Peak VO₂ is a validated surrogate for major clinical outcomes, including hospitalization, transplant, and mortality, and a 10% decline is associated with nearly double the risk of death or transplant in Fontan patients.2"We believe every child and young adult living with Fontan circulation deserves a future with better options," said Dong Hyun 'Dean' Park, Chairman and CEO of Mezzion. "FUEL-2 reflects our deep commitment not only to science but also to the families, clinicians, and advocates who have helped bring this vision to life." To ensure the highest data quality, all cardiopulmonary exercise testing (CPET) in FUEL-2 is centrally reviewed by The Lundquist Institute, an internationally recognized leader in cardiopulmonary diagnostics. This centralized approach enhances consistency and precision in measuring both primary and secondary endpoints across all global sites. FUEL-2 is being conducted at more than 30 of the world's leading children's hospitals across the United States and South Korea. The trial is supported by a global coalition of patient advocacy organizations, clinical investigators, and families dedicated to improving long-term outcomes for individuals with Fontan circulation. Join the Movement Patients and families interested in learning more or joining the study can visit or speak with their care team at a participating center. Clinical sites and investigators are encouraged to continue building on this momentum as we enter the second half of enrollment. Your partnership is critical to delivering the first potential FDA-approved therapy for this vulnerable and resilient community. About Mezzion Mezzion Pharmaceuticals, Inc., a U.S.-based subsidiary of Mezzion Pharma Co., Ltd. (KOSDAQ: 140410), is a late-stage biopharmaceutical company focused on developing life-changing therapies for patients with rare and underserved diseases. Headquartered in New Jersey, Mezzion leads the global clinical development and commercialization of JURVIGO® (udenafil), an investigational therapy currently in Phase 3 trials for patients with single ventricle heart disease and Fontan physiology. The company has received Rare Pediatric Disease Designation from the U.S. FDA and anticipates submitting a New Drug Application (NDA) following completion of the FUEL-2 trial. For more information, visit and . ¹ JURVIGO® (udenafil) is an investigational drug and has not been approved for the treatment of Fontan patients by the U.S. FDA or any other regulatory authority. The safety and efficacy of JURVIGO® in this population have not been established. 2 Cunningham JW, Nathan AS, Rhodes J, Shafer K, Landzberg MJ, Opotowsky AR. Decline in peak oxygen consumption over time predicts death or transplantation in adults with a Fontan circulation. Am Heart J. 2017;189:184–192. Media Contacts: John Presser, EVP, CBO: [email protected] Mr. Sung-Il Noh, CFO: [email protected] SOURCE Mezzion Pharmaceuticals, Inc WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED