United Therapeutics receives FDA clearance for xenoheart clinical trial

United Therapeutics Corporation, a public benefit corporation with co-headquarters in Research Triangle Park, has received U.S. Food and Drug Administration (FDA) clearance under the company’s Investigational New Drug application to proceed with a clinical study of its investigational UHeart xenoheart derived from a pig.

Heart failure affects about 6.7 million U.S. adults, yet only a small fraction of patients are even listed for a donor heart each year, with roughly 4,000 transplants performed. This severe mismatch between demand and supply is driving interest in animal-derived engineered hearts known as xenohearts as a potential way to address the critical shortage of human donor organs.

For the UHeart, six human genes are added to the pig genome to facilitate immunological acceptance and compatibility in a human recipient. Four porcine genes are also inactivated or “knocked out” to reduce the risk of organ rejection and to moderate growth. 

“Moving a porcine-derived heart into human clinical trials represents another defining advancement for the field of xenotransplantation,” said Kristina DeSmet, Ph.D., senior director of product development at United Therapeutics. “The heart is one of the most complex solid organs to transplant, and proceeding into the clinic reflects years of coordinated scientific progress.”

Study details

The clinical study, known as EXPRESS, will initially enroll up to two participants, with United Therapeutics providing the FDA with safety and efficacy data from the first UHeart xenotransplant recipient before enrolling a second participant. 

If the first two transplants are successful, the study could expand and eventually provide the evidence needed for United Therapeutics to seek FDA approval of its genetically modified pig-heart transplant technology. According to the company, this is the first clinical trial of a pig-heart transplant designed with that goal in mind.

The EXPRESS study is designed as a phase 1/2/3 trial — sometimes referred to as a “phaseless” study — to evaluate safety and efficacy without the phased studies associated with conventional drug approvals. Participants will receive a UHeart transplant followed by a 24-week follow-up period during which all study endpoints and safety assessments will be evaluated. After the 24 weeks, participants will be followed for the rest of their lives.

“Patients with end-stage heart disease continue to face profound limitations in available treatment options,” said Noah Byrd, Ph.D., vice president of global regulatory affairs at United Therapeutics. “This FDA clearance to proceed with our EXPRESS clinical trial will allow us to begin evaluating an innovative therapeutic option designed to address this unmet need.”