United Therapeutics Corporation announced the successful completion of the first clinical xenotransplantation in its EXPAND study, marking a historic milestone in transplant medicine. The procedure involved transplanting the company's investigational UKidney into a patient with end-stage renal disease (ESRD) at NYU Langone Health.
Breakthrough in Xenotransplantation Technology
The UKidney represents a significant advancement in xenotransplantation technology, featuring a pig kidney with 10 precise gene modifications. Six human genes have been added to the pig genome to facilitate immunological acceptance and compatibility in human recipients, while four porcine genes have been inactivated or "knocked out" to reduce organ rejection risk and moderate organ growth.
"The first transplant in this first-of-its-kind study marks a watershed moment for United Therapeutics' vision to broaden access to transplantable organs," said Leigh Peterson, Ph.D., Executive Vice President, Product Development and Xenotransplantation at United Therapeutics. "This trial moves us closer to offering ESRD patients an alternative to lifelong dialysis, especially those who are unlikely to receive a kidney from a human donor."
Clinical Trial Design and Endpoints
The EXPAND study (NCT06878560) is structured as a multicenter, open-label, safety and efficacy trial designed to support a Biologics License Application (BLA) with the FDA. The innovative "phaseless" design combines phase 1/2/3 elements to evaluate safety and efficacy seamlessly without traditional phase transitions.
Study participants receive a UKidney transplant followed by a comprehensive 24-week post-transplant follow-up period. After this initial period, recipients continue lifelong monitoring for UKidney function and zoonotic infections.
Primary efficacy endpoints include participant survival rate, UKidney survival rate, changes in measured glomerular filtration rate, and quality of life improvements at 24 weeks post-transplant. Safety endpoints encompass adverse events, serious adverse events, all-cause mortality, and the incidence of proteinuria, zoonotic infections, and opportunistic infections.
Cohort-Based Approach and Patient Selection
The trial employs a careful cohort-based design, with the first cohort consisting of six transplants across two centers. A mandatory 12-week waiting period separates the first and second transplants, allowing for thorough safety assessment. An Independent Data Monitoring Committee will review safety and efficacy data from the initial cohort before determining study progression.
Patient selection criteria are stringent, targeting individuals aged 55 to 70 years with ESRD who have been on hemodialysis for at least six months. Participants undergo crossmatch assay screening to assess immunological compatibility with the UKidney. The protocol excludes patients requiring multiple organ transplants or those with severe comorbidities including advanced cardiovascular disease, severe peripheral vascular disease, chronic pulmonary disease, and uncontrolled diabetes.
Addressing the Organ Shortage Crisis
The clinical advancement comes at a critical time for kidney transplantation in the United States. According to the American Kidney Fund, approximately 815,000 patients currently live with kidney failure, with more than 555,000 on dialysis. Of these, approximately 90,000 are on the U.S. kidney transplant waiting list, while only 22,000 deceased donor kidney transplants occurred in 2024.
The urgency of this unmet medical need is underscored by sobering statistics: a 2021 study found that three years after starting dialysis, only 12% of patients had been placed on an Organ Procurement and Transplant Network kidney transplant waitlist, while more than 40% had died.
"This achievement marks a transformative moment in transplant medicine," said Robert Montgomery, M.D., D.Phil., Chair of the Department of Surgery at the NYU Grossman School of Medicine and Director of the NYU Langone Transplant Institute, who led the transplant team. "The EXPAND study offers new hope to the thousands of Americans currently on the kidney transplant waiting list, many of whom may not survive long enough to receive a human organ."
Future Study Expansion
Following data review from the first six transplants with the FDA, United Therapeutics plans to amend the study protocol to increase the sample size to support BLA submission and include additional transplant centers. This expansion strategy reflects the company's commitment to advancing xenotransplantation as a viable solution to organ shortage while maintaining rigorous safety standards.
