United Therapeutics receives FDA clearance to begin the EXPRESS clinical trial evaluating UHeart™, an investigational genetically engineered porcine-derived heart for patients with advanced end-stage heart failure, marking the first FDA-cleared xenoheart clinical trial intended to support a future BLA submission.
Written By: Chikkula Pavan Kumar, PharmD
Reviewed By: Pharmacally Editorial Team
United Therapeutics Corporation announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application to begin the EXPRESS clinical trial evaluating UHeart™, an investigational genetically engineered porcine-derived heart for patients with advanced end-stage heart failure.
The FDA clearance marks the first formal FDA-cleared clinical trial evaluating a xenoheart intended to support a future Biologics License Application (BLA). The study is designed to generate safety and efficacy data supporting a potential future BLA submission for UHeart™. Previous pig-heart xenotransplants in humans were conducted under emergency or compassionate-use authorizations rather than structured clinical trial protocols.
The EXPRESS study will initially enroll up to two participants at a single center. United Therapeutics will submit safety and efficacy data from the first transplant recipient to the FDA before proceeding with a second transplant. If early outcomes are favorable, the study may later expand to additional centers.
EXPRESS is designed as a seamless adaptive “phaseless” trial, allowing continuous evaluation of safety and efficacy within a single protocol rather than separate phase 1, 2, and 3 studies. Participants will undergo a 24-week post-transplant evaluation followed by lifelong monitoring for survival, graft function, and potential zoonotic infections associated with cross-species transplantation.
UHeart™ is developed from a genetically engineered pig containing 10 targeted gene edits intended to improve compatibility between the donor organ and human recipients. The donor pig includes six inserted human genes designed to improve immunological compatibility and four inactivated porcine genes intended to reduce rejection risk and help control post-transplant organ growth.
Key efficacy endpoints include participant survival, UHeart™ graft survival, cardiac function, exercise capacity, and quality-of-life improvement at 24 weeks. Safety assessments include adverse events, arrhythmias, thromboembolic complications, ischemic stroke events, opportunistic infections, and zoonotic infection monitoring. An independent Data Monitoring Committee (DMC) will oversee safety and efficacy findings throughout the study.
Kristina DeSmet, Ph.D., Senior Director of Product Development at United Therapeutics, stated that advancing a porcine-derived heart into human clinical trials represents a major milestone for xenotransplantation.
Advanced heart failure remains a major unmet medical need. According to the Journal of Cardiac Failure, nearly 6.7 million adults in the United States are living with heart failure. In 2023, approximately 8,000 patients were waitlisted for heart transplantation in the U.S., while only around 4,000 heart transplants were performed.
United Therapeutics stated that xenotransplantation technologies such as UHeart™ are being developed to help address the ongoing shortage of donor organs and expand access to life-saving transplant options. The company is also developing additional xenotransplantation programs involving kidneys and lungs as part of its broader effort to address donor organ shortages.
Reference
About the Writer
Chikkula Pavan Kumar (LinkedIn), PharmD is a Doctor of Pharmacy with a keen interest in clinical pharmacy, pharmacovigilance, and evidence-based practice. In his words, he is passionate about patient safety and translating complex medical information into clear, research-driven communication.