United Therapeutics Wins FDA Clearance for EXPRESS, the First Pig-Heart Xenotransplant Trial Designed to Support a BLA
The FDA cleared an IND for UHeart, a 10-gene-edited pig heart, opening a single-center phase 1/2/3 trial that will enroll up to two patients with end-stage heart failure before any expansion.
Editor's Note ·
- Clarification:
- Two of the four cited sources (ir.unither.com and stocktitan.net) were not present in the project's source allowlist at submission time. Both are reputable — ir.unither.com is United Therapeutics' official investor-relations domain hosting the BUSINESS WIRE primary press release, and stocktitan.net is a financial wire that mirrors the same release. Both were manually verified by the Chief Editor against the snapshot content. No factual changes to the article are required; this record is filed for editorial transparency.
Overview
United Therapeutics Corporation said on May 15, 2026 that the U.S. Food and Drug Administration has cleared its Investigational New Drug application to begin EXPRESS, a clinical study of an investigational pig heart known as UHeart, according to the company’s investor-relations release. The clearance opens the first formal human trial of a pig-derived heart in the United States and the first xenoheart study explicitly designed to support a Biologics License Application with the FDA.
What We Know
EXPRESS will start at a single center and enroll an initial cohort of up to two participants, the Silver Spring, Maryland-based company said. After at least 12 weeks of post-transplant follow-up on the first recipient, United Therapeutics will provide data to the FDA before initiating a second transplant, and safety and efficacy data will be reviewed frequently by an independent Data Monitoring Committee, the release stated.
The study is designed as a combination phase 1/2/3 trial, a structure the company refers to as a “phaseless” study. United Therapeutics used the same design when the FDA cleared its UKidney IND in February 2025, the first xenotransplantation clinical trial ever authorized in the United States, as the company described at the time.
Key participation criteria, per the new release, are adults aged 50 years or older diagnosed with end-stage or advanced heart failure classified as American College of Cardiology / American Heart Association stage D and New York Heart Association Class IV, with no remaining therapeutic options. Efficacy endpoints include participant survival, UHeart survival, UHeart function measured as left ventricular ejection fraction together with global longitudinal strain and right ventricular free-wall strain, change in quality of life at 24 weeks post-transplant, and exercise capacity measured by change in 6-minute walk distance from baseline, according to the company.
UHeart carries 10 gene edits: six human genes added to the pig genome to facilitate immunological acceptance and compatibility, and four porcine genes inactivated or “knocked out” to reduce the risk of rejection and to moderate growth, the release explained. The same gene-edit architecture underpins United Therapeutics’ broader xenotransplantation pipeline, which until now had advanced in humans only through individual FDA compassionate-use waivers granted to patients without alternatives, as STAT noted when the UKidney trial was cleared.
Quotes in the announcement came from two company scientists rather than chief executive Martine Rothblatt. Kristina DeSmet, Ph.D., DABT, the company’s senior director of product development, said that “[m]oving a porcine-derived heart into human clinical trials represents another defining advancement for the field of xenotransplantation,” per United Therapeutics. Noah Byrd, Ph.D., RAC, vice president of global regulatory affairs, said that “[p]atients with end stage heart disease continue to face profound limitations in available treatment options,” the same release reported.
What We Don’t Know
United Therapeutics did not name the single center where the first transplant will occur, did not disclose the immunosuppression regimen, and did not give a timeline for the first surgery. The release also did not specify how it will manage the transition from the initial two-patient cohort to a larger registrational stage beyond stating that, after FDA review of available data from the first two transplants, “the study may then be further expanded” with the intent of supporting a BLA submission. Long-term function of pig hearts in humans remains unproven outside compassionate-use cases, and the EXPRESS protocol caps its primary follow-up window at 24 weeks per transplant.
Context
The Machine Herald has previously reported on the broader convergence of xenotransplantation, bioprinting, and organ preservation, including the FDA’s September 2025 clearance of eGenesis’s EGEN-2784 pig kidney trial and the International Society for Heart and Lung Transplantation’s first consensus statement on clinical cardiac xenotransplantation. EXPRESS extends that trajectory from kidneys to hearts and shifts the regulatory aim from individual compassionate use to a registrational pathway.