NYU Langone Health begins first clinical trial of gene-edited pig kidney transplants

The first surgery in a clinical trial testing the safety and efficacy of gene-edited pig kidney transplants in patients with end-stage renal disease was recently performed at NYU Langone Health.

The study, known as EXPAND (NCT06878560) and sponsored by United Therapeutics Corporation, is testing an investigational xenokidney from a pig with 10 gene edits that is known as the UKidney. Six human genes are added to the pig genome to ensure it has the best chance of being accepted in a human recipient. Four porcine genes are inactivated or "knocked out" to reduce the risk of organ rejection and to moderate organ growth.

Leigh Peterson, PhD, executive vice president, product development and xenotransplantation at United TherapeuticsThe first transplant in this first-of-its-kind study marks a watershed moment for United Therapeutics' vision to broaden access to transplantable organs. This trial moves us closer to offering end-stage renal disease patients an alternative to lifelong dialysis, especially those patients who are unlikely to receive a kidney from a human donor. Our team is grateful for the collaboration that made this possible, and we remain focused on patient safety and scientific progress as the study continues."

In April 2024, a patient received the first-ever combined heart pump implantation and gene-edited pig kidney transplant at NYU Langone. The recipient later died under hospice care in July of that year after difficulty difficulty tapering in-patient medicines used to maintain a high enough blood pressure to support the xenokidney. In November 2024, another xenokidney recipient received a 10-gene-edited pig kidney at NYU Langone and returned home to Alabama. The recipient's pig kidney was removed in April 2025 after it stopped functioning properly due to complications from an unrelated infection, and she resumed dialysis treatment.

About the clinical trial

If successful, the EXPAND study is intended to support an eventual Biologics License Application (BLA), to be submitted by United Therapeutics to the U.S. Food and Drug Administration seeking approval of the UKidney. It is designed as a combination phase 1/2/3 trial (sometimes referred to as a "phaseless" study) to evaluate safety and efficacy seamlessly without moving through the separate phase 1, phase 2, and phase 3 studies that are typically associated with conventional drug approvals.

Study participants will receive a UKidney transplant followed by a 24-week posttransplant follow-up period, including the evaluation of all study end points and safety assessments. After the 24-week posttransplant follow-up period, participants who received a UKidney will continue to be followed for the rest of their lives, including monitoring for UKidney function and zoonotic infections.

Efficacy end points include participant survival rate, UKidney survival rate, change in measured glomerular filtration rate, and change in quality of life in participants at 24 weeks posttransplant. Overall survival time of participants receiving a UKidney and overall survival time of the UKidneys themselves are also efficacy end points. Safety end points include the incidence of adverse events and serious adverse events, all-cause mortality, and the incidence of proteinuria, zoonotic infections, and opportunistic infections.

The first cohort will consist of six transplants at two centers. There will be a 12-week waiting period between the first and second transplants. After the initial cohort reaches at least 12 weeks posttransplant, safety and efficacy data will be reviewed by an Independent Data Monitoring Committee to determine if the study should proceed to the next cohort.

After reviewing the data from the first six transplants with the FDA, United Therapeutics plans to amend the study protocol to increase the study sample size to support a BLA and include additional transplant centers.

Additional key participation criteria include an age of 55 to 70 years old, a diagnosis of end-stage renal disease, and at least six months on hemodialysis. Participants will be screened using a crossmatch assay to assess expected immunological compatibility with the UKidney. Participants must not need multiple organ transplants; must not have severe medical comorbidities, such as advanced cardiovascular disease, severe peripheral vascular disease, severe neurological disease, chronic pulmonary disease, and uncontrolled diabetes; and must not have a history of medical noncompliance that may preclude adherence to the demands and requirements of xenotransplantation.

Source:

NYU Langone