Mezzion Pharma Submits Protocol for Confirmatory Pivotal Phase 3 Trial ("FUEL-2") in Fontan Subjects

SEOUL, South Korea, Feb. 21, 2023 /PRNewswire/ -- Mezzion Pharma Co., Ltd. (Mezzion Pharma) has submitted a confirmatory pivotal Phase 3 Clinical Trial in Fontan subjects to the Food and Drug Administration (FDA).

In the Type B meeting between the FDA and Mezzion, the FDA provided Mezzion with a clear path forward to FDA approval for the treatment of Fontan subjects with udenafil. In the Type B meeting, an agreement was reached with the FDA regarding its requirement for a confirmatory Phase 3 clinical trial. Mezzion reports that it has submitted a new protocol for the FUEL-2 Trial to the Division of Cardiology and Nephrology consistent with the agreement reached with the FDA in Type B meeting.

The cardiovascular efficiency of the Fontan subjects deteriorates through adolescence and into adulthood. This deterioration correlates with a decline in exercise capacity and an increase in the prevalence of heart failure symptoms, hospitalization and mortality. Mezzion believes that the FUEL-2 confirmatory trial in Fontan subjects will show that chronic udenafil therapy will improve their exercise capacity and thus potentially prolong the time to the onset of serious morbidity.

The protocol for the FUEL-2 Trial is based on what was learned from the original Phase 3 trial FUEL Trial and the agreement reached with the FDA. The study population will be single ventricle heart disease subjects with Fontan palliation and Fontan physiology who will most likely improve their exercise capacity based on their baseline cardiopulmonary exercise testing performance. Under the revised inclusion/exclusion criteria, FUEL-2 will exclude those target subjects who are defined as "Super Fontans."

The Ad Hoc analysis of a similar population of about 300 subjects excluding the Super Fontans in the original FUEL trial, comparing the mean peak VO₂ of the udenafil treated group of about 150 subjects versus the placebo group of also about 150 subjects was statistically significant at a p-value of 0.023. The important secondary endpoints of exercise capacity at the Ventilatory Anaerobic Threshold ("VAT"), Work Rate, Oxygen Consumption at VAT and Ventilatory Efficiency will also be evaluated. These secondary endpoints were all statistically significant for the entire treatment arm, about 200 subjects, in the FUEL Trial.

FUEL-2 is designed as a double-blind, placebo-controlled trial with a sample size of approximately 400 subjects. The primary efficacy endpoint is the change in peak oxygen consumption (VO₂ mL/kg/min) from Baseline to Week 26, as measured by maximal cardiopulmonary exercise testing. As agreed with the FDA, the statistical criteria for success will be at a 2-sided level of significance of 10% (p<0.1). An interim analysis will be conducted when approximately 50% of the subjects complete the trial to determine what final sample size is needed to meet the statistical criteria of a 2-sided alpha of 0.1 at 90% power. 

Because the principal objective of FUEL-2 is to obtain statistical significance of the primary end point, FUEL-2 will have fewer procedures compared to the FUEL Trial. Mezzion therefore believes that the FUEL-2 protocol is simpler and more straightforward than the FUEL Trial protocol. Mezzion also believes that the FUEL-2 protocol will be more convenient for the subjects, it will facilitate and expedite the clinical operation at the site level, and it will streamline the enrollment and recruitment process. 

Approximately 30 sites throughout the world will participate in the new FUEL-2 confirmatory trial. Study enrollment is expected to be initiated within the next few weeks.

About the Fontan Procedure and Subsequent Expectations

The Fontan procedure is a surgical intervention that allows for the survival of children born with congenital heart disease characterized by only a single functional pumping chamber. This procedure consists of re-configuring the circulation to allow the single ventricle to pump blood to the body while connecting the great veins directly to the arteries that bring blood to the lungs. In this "Fontan circulation" the blood returning from the body bypasses the heart and travels to the lungs without the assistance of a dedicated right ventricle pumping chamber. The goal of the Fontan procedure is to separate the systemic and pulmonary circulations and to improve oxygen levels by redirecting venous blood directly to the lungs.

While the Fontan procedure creates a stable circulation, the risk of hospitalization and cardiac death rises significantly in the second and third decades after Fontan completion, a risk that is associated with a decline in exercise capacity. The Fontan circulation is also associated with non-cardiac complications such as protein-losing enteropathy, plastic bronchitis, and liver failure, all of which can be attributed to a chronic elevation in central venous pressure and a chronically reduced cardiac output. For all of these reasons, a 35-year-old patient who has gone through Fontan palliation has the approximate life expectancy of a 75-year-old with normal, but serious age-advanced, cardiac physiology.

Mezzion Pharma Co., Ltd.

Mezzion Pharma Co., Ltd. is headquartered in Korea. Mezzion and its wholly owned subsidiary, Mezzion Pharmaceuticals, Inc., have administrative offices in Deerfield, Illinois and Boca Raton, Florida. Mezzion Pharma is an innovation-driven pharmaceutical company that is focused on discovering, developing, and commercializing novel therapeutics in the field of rare pediatric diseases. Mezzion Pharma is a publicly-listed pharmaceutical company in Korea on the Korean stock exchange under (140410:KOSDAQ).

Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding: Mezzion Pharma's expectations regarding the potential benefits of udenafil; Mezzion Pharma's expectations regarding the anticipated timing of any future clinical trials; Mezzion Pharma's expectations on regulatory submissions for marketing approval of udenafil for the treatment of patients that have undergone the Fontan operation, to improve exercise capacity in the United States, including the timing of these submissions; and Mezzion Pharma's expectations regarding the potential commercial launch of udenafil, including the timing of a potential approval of udenafil. Risks and uncertainties that contribute to the uncertain nature of the forward-looking statements include: the expectation that Mezzion Pharma will need additional funds to finance its operations; Mezzion Pharma's or any of its collaborative partners' ability to initiate and/or complete clinical trials; the unpredictability of the regulatory process; the possibility that Mezzion Pharma's or any of its clinical trials will not be successful; Mezzion Pharma's dependence on the success of udenafil; Mezzion Pharma's reliance on third parties for the manufacture of Mezzion Pharma's udenafil and udenafil tablets; possible regulatory developments in the United States and foreign countries; and Mezzion Pharma's ability to attract and retain senior management personnel.

These and other risks and uncertainties are described more fully in Mezzion Pharma's most recent filings with the Statements under the Private Securities Litigation Reform Act: with the exception of the historical information contained in this release, the matters described herein contain forward-looking statements that involve risk and uncertainties that may individually or mutually impact the matters herein described, including but not limited to FDA review and approval, product development and acceptance, manufacturing, competition, and/or other factors, which are outside the control of Mezzion Pharma. All forward-looking statements contained in this press release speak only as of the date on which they were made. Mezzion undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

Contact:
Dr. James Yeager, Deerfield, Illinois, USA, Tel: +1-847-2122679
Email: [email protected]

Mr. S.I. Noh, Seoul, Korea, Tel: +82 2 560 8000
Email: [email protected]

SOURCE Mezzion Pharma Co. Ltd.