Genetically modified pig kidneys with up to 69 genomic edits are set to be transplanted into patients with end-stage renal disease in 2025 to assess the strategy's long-term viability and immunogenic compatibility.
The U.S. Food and Drug Administration (FDA) has approved the first-in-human clinical trials evaluating genetically modified porcine kidney transplantation for patients with end-stage renal disease (ESRD). United Therapeutics Corporation and eGenesis received regulatory clearance to initiate these trials in 2025, with findings expected to inform the feasibility, immunological compatibility, and long-term viability of xenotransplantation.
United Therapeutics will enroll 6 patients with ESRD who have been on dialysis for 6 months or more and have no significant comorbidities; if early safety and efficacy endpoints are met, the trial will expand to 50 participants. eGenesis' trial will begin with three patients and increase enrollment in a staggered manner. Patients will be monitored for 24 weeks post-transplant, with lifelong follow-ups to assess health outcomes and potential zoonotic risks, according to The New York Times.
The porcine kidneys used in these trials have undergone extensive genetic modification to enhance their compatibility with the human immune system. United Therapeutics' donor pigs have been engineered with 10 genetic modifications: the deletion of 4 porcine genes implicated in hyperacute rejection, and the addition of 6 human transgenes to attenuate immune response. eGenesis' approach involves 69 genomic edits, primarily to disable viruses that may present a risk to human recipients. Both companies utilize pathogen-free breeding facilities with stringent biosecurity measures, including routine pathogen screening.
In the United States, more than 550,000 individuals have ESRD, and nearly 100,000 remain on the kidney transplant waiting list. In 2023, fewer than 25,000 kidney transplants were performed. Researchers are investigating xenotransplantation as a potential approach to increase organ availability.
United Therapeutics aims to initiate transplants by mid-2025, with several months between procedures to evaluate outcomes before proceeding. eGenesis will employ a similar timeline, spacing transplants at 6-month and 3-month intervals.
Ethical concerns remain, particularly regarding informed consent in dialysis patients considering xenotransplantation, as well as the potential risks of undetected zoonotic pathogen transmission. Cost and insurance coverage associated with xenotransplantation also remain unclear.