Confirmatory Phase 3 trial for Udenafil expands to Europe; targets H2 2027 for results and FDA filing
Company estimates peak annual U.S. sales of $3 billion; simultaneous preparations for production and insurance coverage underway
Mezzion Pharma (140410.KQ) is advancing its bid to develop the first FDA-approved treatment for patients who have undergone the Fontan procedure. By expanding its confirmatory Phase 3 trial, FUEL-2, for the oral candidate "Udenafil" into Europe, the company is broadening its patient recruitment base while simultaneously preparing the manufacturing and insurance frameworks required for post-approval sales. Mezzion plans to leverage the data and expertise accumulated through global clinical trials to directly lead the authorization and commercialization processes, while applying these capabilities to its follow-on drug pipeline.
Since beginning Phase 1 and 2 trials for Fontan patients in the United States in 2014, Mezzion has continued its development through global Phase 3 trials, regulatory preparation, and supplemental studies. From 2023 to 2025, the company’s consolidated R&D expenditure is estimated at approximately 50 billion KRW, reflecting the significant capital invested in sustaining long-term development.
Bridging the Treatment Gap Post-Surgery; Targeting Improved Exercise Capacity
The Fontan procedure is a surgical intervention that reroutes blood circulation in patients with congenital heart defects where only one ventricle is functional. Following the surgery, blood must pass through the lungs without the pumping action of a ventricle to push it toward the pulmonary system, making pulmonary vascular resistance a critical factor in circulation. In this circulatory structure, exercise capacity often declines as patients grow, creating a need for therapeutic means to manage functional deterioration post-surgery.
Udenafil is a PDE5 inhibitor designed to relax pulmonary blood vessels, thereby lowering pulmonary vascular resistance to facilitate smoother blood flow and improve exercise capacity. Mezzion estimates there are approximately 35,000 Fontan patients in the United States. In the absence of an FDA-approved treatment specifically indicated for Fontan patients, Udenafil could become a vital new therapeutic option upon approval.
Refining Study Design from Initial Clinical Experience; Target for FDA Filing in H2 2027
The FUEL-2 trial incorporates the achievements and lessons learned from previous clinical efforts. The initial Phase 3 trial, FUEL, did not meet statistical significance for its primary endpoint—peak oxygen consumption (VO2 peak) at maximum exercise—across the entire patient population. However, it did show improvement in certain secondary endpoints evaluating exercise intervals before reaching maximum intensity. Subsequently, researchers analyzed how drug response varies based on a patient’s baseline exercise capacity, using these insights to refine the patient selection criteria for the follow-on trial.
This approach is supported by post-hoc analysis results. A paper published in the Journal of the American Heart Association in 2025 revealed that Udenafil showed significant improvement over the placebo in a subgroup of patients whose peak oxygen consumption was less than 80% of the predicted normal value. FUEL-2 is designed to recruit patients between 45% and 80% of their predicted normal capacity, excluding those whose exercise capacity is already near normal to verify efficacy in the population most in need of improvement. The trial involves approximately 436 patients aged 12 to 18 who have undergone the Fontan procedure. After a 26-week administration of Udenafil or a placebo, changes in peak oxygen consumption will be compared via cardiopulmonary exercise testing (CPET).
The clinical network supporting recruitment is also expanding. On October 1, Mezzion began patient recruitment for FUEL-2 at Great Ormond Street Hospital in London. The company plans to expand its recruitment base to 14 hospitals across six European countries, including the UK, France, Italy, Germany, the Netherlands, and Slovakia. Mezzion intends to utilize its cooperation with these specialized medical institutions, which provide intensive care for Fontan patients, for future European authorization and market entry.
In June, Mezzion announced that an independent blinded statistical review concluded there was no need to increase the target sample size. Maintaining the planned recruitment scale, the company aims to complete patient enrollment by the end of 2026, with the goal of announcing topline results and submitting a New Drug Application (NDA) to the FDA in the second half of 2027. Following the end of recruitment, final results will be derived after the 26-week dosing period for the last patient, followed by data verification and analysis.
Manufacturing and Insurance Preparations; Peak U.S. Sales Estimated at $3 Billion
In alignment with the filing schedule, Mezzion is concurrently securing clinical data and preparing for manufacturing and quality control (CMC). In a notice on July 10, the company stated it had completed production orders for two batches of the active pharmaceutical ingredient (API). Mezzion plans to pursue manufacturing and quality discussions with the FDA based on data from these new batches and is also preparing mock inspections in anticipation of pre-approval plant audits. According to its business report, Mezzion partners with Polpharma in Poland for API production and Halo Pharma in Canada for the finished dosage form, establishing a structure for regulatory review and commercial supply through external manufacturing facilities.
Alongside production readiness, Mezzion is refining its U.S. pricing and sales strategy. In its business report, based on surveys of Pharmacy Benefit Managers (PBMs) and the pricing of similar drugs, Mezzion projected an estimated annual price for Udenafil of approximately $180,000. Based on these pricing projections and patient population assumptions, the company estimates peak annual sales in the U.S. market at approximately $3 billion. This figure, included in a written response from the company’s IR representative released by Small Insight Research in January 2026, refers to the year sales reach their peak as prescriptions expand post-approval. The projected price is not yet a finalized launch price, and actual revenue may vary depending on the scope of approval, insurance negotiations, and the number of prescribed patients.
To support the expansion of prescriptions, the company is preparing insurance coverage and patient co-pay assistance programs. The plan is to increase accessibility so that patients do not abandon treatment due to cost burdens, while turning the collaborative relationships built with specialized medical institutions during the clinical trials into a sales foundation. Specifically, Mezzion aims to leverage the market characteristic where Fontan patients are concentrated in specific treatment centers to deliver product information through specialized medical staff, enhancing sales and marketing efficiency during the initial launch phase.
For regions outside the United States, Mezzion is considering commercialization through partnerships. The company stated that at BIO USA in June, it discussed prescription accessibility, launch readiness, and regional commercialization strategies with global pharmaceutical firms. By leading the clinical and regulatory process while establishing tailored sales and cooperation models for each market, Mezzion intends to broaden its business scope.
Accumulated Development Capabilities; Expanding to Follow-on Renal Disease Treatments
The data and experience gathered from developing the Fontan treatment are now being applied to follow-on indications. The field where Mezzion is expanding its scope is Autosomal Dominant Polycystic Kidney Disease (ADPKD). This is a hereditary condition where cysts form and grow in the kidneys, leading to functional decline. In May, Mezzion announced it had received a written opinion from the FDA during a pre-IND meeting, stating that existing non-clinical data and the clinical and safety experience of Udenafil could serve as a reasonable basis for supporting clinical development for ADPKD.
Mezzion has set a goal to commence Phase 2 trials for ADPKD within the year and announced in September that it had completed the establishment of a U.S. subsidiary dedicated to the global development and commercialization of the treatment. By having the local entity manage global clinical operations and FDA consultations, Mezzion plans to add a U.S.-based development system to its existing drug data to prepare for the start of clinical trials for the follow-on indication.
Mezzion’s challenge is evolving from the first commercialization of a Fontan treatment to the development of subsequent indications. Proving efficacy in FUEL-2 and commencing sales following FDA approval would allow the company to convert long-term R&D investment into revenue, while the ADPKD program offers an opportunity to expand its business footprint using existing data and its U.S. infrastructure. Advancing clinical trials alongside production and sales readiness while securing a foundation for follow-on development remains the key task for its future growth.
