FDA greenlights first clinical trials for genetically modified pig kidney transplants in humans

Earlier this week, two companies reported they have received approval from the Food and Drug Administration (FDA) to conduct trials transplanting genetically modified pig kidneys into patients with kidney failure. These trials will allow researchers to study how well the pig kidneys work and how safe they are for human patients.

The companies that have received clearance for these in-human xenotransplantation (transplanting organs or tissues from one species into another) trials are United Therapeutics and eGenesis. The United Therapeutics pig kidney, which the company is calling UKidney™, comes from a 10 gene-edited source pig while eGenesis uses a 69 gene-edited source pig. According to The New York Times, "six human genes were added [to UKidney] and four genes [from the pig] were inactivated — one that restricts the organs' growth and three that can cause human rejection. The eGenesis pigs have undergone 69 gene edits, including changes in 59 genes to inactivate viruses that are integrated into the pig's genome."

"We are entering a transformative era in organ transplantation," Mike Curtis, president and chief executive of eGenesis, told The New York Times.

According to the press release announcing the news, the United Therapeutics trial is expected to start in mid-2025. The trial will begin by transplanting the UKidney into six patients with end-stage renal disease (ESRD or kidney failure) and then expand to 50 patients. Participants in the trial will need to have been diagnosed with ESRD, been on dialysis for at least six months and be between the ages of 55 and 70. United Therapeutics also said patients in the trial will be part of two groups:

• ESRD patients who have been assessed and determined to be ineligible for a conventional allogeneic (genetically different, though belonging to the same species) kidney transplant for medical reasons; and
• ESRD patients who have been on the kidney transplant waitlist but are more likely to die or go untransplanted than receive a deceased donor kidney transplant within five years.

"Clearance of our [Investigational New Drug application (IND)] for this first-ever clinical trial of a xenokidney represents a significant step forward in our relentless mission to expand the availability of transplantable organs," said Leigh Peterson, Ph.D., executive vice president, product development and xenotransplantation at United Therapeutics, in the press release. "Our goal is to increase the availability of transplantable organs to offer a therapeutic alternative to a lifetime on dialysis for a large population of patients who are unlikely to receive an allogeneic 3 kidney transplant."

The eGenesis trial is a three-patient trial that is part of a FDA-authorized Expanded Access Protocol study. The Expanded Access program is often called the "compassionate use program" and allows investigational medical products to be used outside of clinical trials when a patient has a life-threatening condition. Dr. Curtis told The New York Times that the study's patients will be people "living with kidney failure who are unlikely to receive a human organ within five years." The newspaper also reported that the company indicated there "will be a six-month waiting period between the first and second patient, and then a lull of three months after that before the third."

These are the first multi-patient trials to study the possibility of using pig kidneys in humans, but it will not be the first time a patient has received a pig kidney. On March 16, 2024, Massachusetts General Hospital performed the first kidney transplant of a genetically-modified pig kidney into a living person. He died about two months after the transplant, although doctors said the kidney was not the cause of his death. Additionally, a woman in New Jersey received a pig kidney and heart transplant in April 2024, but it was removed 47 days after the surgery because the organ was failing. 

Most recently, Towana Looney, age 53, from Alabama received the third gene-edited pig kidney at NYU Langone on Nov. 25, 2024. She was discharged from the hospital 11 days later and at the time of the publication of this blog post, she is still doing well and is now the longest-living person with a pig kidney.

Researchers hope that these studies will provide more data and advance their understanding of the potential of xenotransplantation as a possible solution to the organ shortage. There are more than 92,000 Americans on the kidney transplant waiting list, but last year, less than 29,000 were able to get a kidney transplant. The shortage of available donor kidneys also means that most people who develop kidney failure are treated with dialysis. Of the roughly 130,000 Americans newly diagnosed with kidney failure in 2022, about 3% were able to receive a transplant before starting dialysis, or a preemptive kidney transplant.