In late February, Towana Looney, 53, returned home to Alabama with normal kidney function 3 months after receiving a pig kidney xenotransplant at New York University (NYU) Langone Health in New York City. “I feel blessed,” said Looney in a statement released by NYU Langone Health, where she received the transplant (1). “I’m so grateful to be alive and thankful to have received this incredible gift. It couldn't have happened without God and the amazing team of doctors, nurses, and researchers who have been by my side.”
Looney had donated a kidney to her mother in 1999 but later developed kidney failure as a result of preeclampsia during pregnancy. She began dialysis in 2016 and joined the waiting list for a transplant in 2017 but had been unable to find a match due to a high level of sensitization. She was also developing heart and vascular complications from long-term dialysis. Looney was able to receive the xenotransplant under an expanded access application from the US Food and Drug Administration (FDA), filed by Jayme Locke, MD, MPH, who at the time was treating Looney as a transplant surgeon at The University of Alabama at Birmingham (UAB). Locke, who is now a clinical faculty member at NYU, partnered with Robert Montgomery, MD, DPhil, the H. Leon Pachter, MD, Professor of Surgery; chair of the NYU Grossman School of Medicine; chair of the Department of Surgery; and director of the NYU Langone Transplant Institute, to complete the transplant at NYU.
After her xenotransplant, Looney was hospitalized for 11 days and then closely monitored for 3 more months on an outpatient basis. Her clinicians successfully reversed an early episode of rejection. She will receive ongoing monitoring from physicians at UAB and monthly checkups at NYU. “She has done very well,” Montgomery said. “It is really exciting—the success story that we really needed.”
Montgomery said the success of Looney's transplant helped pave the way for FDA to approve the first human clinical studies of pig-to-human transplantation. A three-patient pilot study is underway at Massachusetts General Hospital in Boston using genetically engineered pig kidneys developed by eGenesis (2). The first patient received a transplant in February. United Therapeutics has also received FDA clearance to launch a six-patient phase 1–2 safety clinical trial using the company's genetically engineered pig kidney (3). If the results in the first 6 patients are promising, the company has clearance to expand the trial to up to 50 patients.
From progress to pilot
The studies mark a major leap forward for kidney xenotransplantation after three decades of research in animal models. In recent years, developments in genetic engineering and immunosuppression have enabled primate animal models to survive for up to 2 years with a transplanted pig kidney and are continuing to help refine the procedure (4). Those successes led Locke and Montgomery to develop and test the genetically engineered pig kidney transplants in decedent human models, providing preliminary proof of concept (5, 6).
A series of genetically engineered pig-to-human heart and kidney transplants conducted under compassionate use exemptions for patients with few options has helped clinicians and scientists further refine their methods. Before Looney, Richard Slayman received a genetically engineered pig kidney at Massachusetts General in March 2024, which lasted for 2 months without signs of rejection before he died of heart complications.
“We were able to learn that the pig kidney can maintain all the important balances required by the kidney, including water balance and mineral balance in a manner very similar to a human kidney,” Leonardo V. Riella, MD, PhD, medical director for kidney transplantation at Massachusetts General Hospital, said. The transplant also found no evidence of transmission of pig viruses, a key concern with xenotransplant.
The eGenesis pilot study will allow Riella and his colleagues to see how well the genetically engineered pig allografts perform in patients with a greater chance of long-term success because they have fewer comorbidities and less time on dialysis than previous recipients.
In late January, Tim Andrews, 66, became the first of three patients to receive a genetically engineered pig kidney created by eGenesis as part of the pilot study. Andrews had been on dialysis for more than 2 years and was struggling with fatigue and severe dialysis complications that included a heart attack in 2023. As a patient with a rare O blood type, Andrews faced a long and uncertain wait for a human allograft. His low chance of receiving a human allograft and his dialysis-related complications made him a candidate for the study. “As soon as I woke up after the surgery, the cloud of dialysis disappeared,” Andrews said in a statement from eGenesis released after the procedure (7). “I felt re-energized and revitalized. It was a miracle.”
The eGenesis kidneys have been genetically edited to remove three pig antigens that would otherwise trigger hyperacute rejection. They also have seven human genes to reduce the human immune response, reduce inflammation, and reduce clotting caused by incompatibility, according to the company. Numerous endogenous pig retroviruses have also been removed from the pig's genome to reduce the risk of infection with a pig virus.
Andrews and other patients in the pilot study will also receive an immunosuppression regimen that includes tegoprubart, an investigational monoclonal antibody targeting the CD40L pathway, to help increase safety and reduce immune suppression side effects.
“[Tegoprubart] is important because it blocks antibody production and so prevents antibody mediator rejection, but it also is capable of controlling the innate immune system, which is our more primitive part of the immune system that we believe is also important and potentially could cause or contribute to rejection in the case of xenotransplantation,” Riella said.
When Kidney News spoke to Riella, Andrews had been off of dialysis for 41 days and had seen his energy skyrocket, allowing him to go to the gym and take his dog for long walks. He also reports being able to think more clearly, Riella said.
Riella and his colleagues are in the process of recruiting the next two patients. They are hoping that the data that they collect from these first three patients over 6 months will provide sufficient data to support their application to launch a larger trial this year.
New era
The studies mark a major leap forward for kidney xenotransplantation after three decades of research in animal models.
The United Therapeutics clinical trial is designed to seamlessly progress through phases 1, 2, and 3. The first transplant is expected by mid-2025. Two groups of patients will be eligible for participation in the trial: those who have been turned down for the human allograft waitlist and those on the waitlist who have a higher likelihood of dying or being de-listed before undergoing transplant.
The trial will use United Therapeutics’ xenokidney called UKidney, which has 10 gene edits. Montgomery noted that many of the edits are similar to those in the eGenesis kidneys. One difference, he said, is that United Therapeutics’ kidneys come from larger pigs and have edits to growth hormone genes to prevent the organ from growing too large.
According to Montgomery, six patients at two centers will receive transplants and be monitored for zoonosis transmission, allograft longevity and function, and signs of rejection during the first two phases. To help minimize the chance of rejection, the team will use an immunosuppression regimen that includes a complement inhibitor and the costimulatory inhibitor belatacept in addition to more traditional immunosuppressive drugs. Montgomery said the regimen is similar to that currently used in highly sensitized transplant recipients.
If a good proportion of the allografts are still functioning well after 6 months, and there are no major safety signals, the company will engage with FDA before progressing into the phase 3 trial with more patients and more centers participating.
Riella said the two clinical studies testing slightly different approaches should provide valuable information about which gene edits or immunosuppressive approaches provide the best results. “We are eager to learn from each other and keep pushing the field forward,” he said.
If the clinical studies are successful, it could herald a new era in kidney transplantation. “It's going to be transformative,” Montgomery said. “It could end the waitlist. It could end death on the waitlist.”
Both teams cited collaboration among academic centers, industry, and FDA with rapidly advancing the field and helping to overcome what once felt like insurmountable hurdles. Riella highlighted frequent data sharing with FDA to increase the agency's confidence in the trial and create opportunities for agency leaders to provide feedback in real-time. “It's a true partnership,” he said. “We’ve been very transparent in sharing everything that we’ve been learning on a weekly basis with [FDA].”
Patients have also played a pivotal role in advancing xenotransplant into trials. Riella and Montgomery have seen a high level of enthusiasm from patients and received inquiries about participation in the studies. Riella said he and his colleagues were unsure what the response would be to an experimental therapy with no guarantees about how long the allografts would last, but patients have been overwhelmingly supportive. He said it reflects the impact of dialysis on patients’ lives and how eager patients are for better options.
“They are the ones advocating for us to keep pushing and [to] move forward so [that] this can be an alternative option to dialysis,” Riella explained. “The support and all the messages [that] we received definitely told us that they’re looking for alternatives, and they want it soon.”
References
- 1.↑
NYU Langone Health. Pig kidney recipient returns home after transplant breakthrough at NYU Langone Health. February 25, 2025. Accessed March 10, 2025. https://nyulangone.org/news/pig-kidney-recipient-returns-home-after-transplant-breakthrough-nyu-langone-health
- 2.↑
eGenesis. eGenesis announces second patient successfully transplanted with genetically engineered porcine kidney. February 7, 2025. Accessed March 10, 2025. https://egenesisbio.com/press-releases/egenesis-announces-second-patient-successfully-transplanted-with-genetically-engineered-porcine-kidney/
- 3.↑
United Therapeutics. United Therapeutics Corporation announces FDA clearance of its investigational new drug application for the UKidney xenotransplantation clinical trial. February 3, 2025. Accessed March 10, 2025. https://ir.unither.com/press-releases/2025/02-03-2025-120011819
- 4.↑
Karadagi A, et al. 412.1: Long-term (2 years) survival of porcine to nonhuman primate life-sustaining kidney xenotransplantation. Transplantation 2023; 107:173. https://journals.lww.com/transplantjournal/fulltext/2023/10002/412_1__long_term__2_years__survival_of_porcine_to.252.aspx
- 5.↑
Porrett PM, et al. First clinical-grade porcine kidney xenotransplant using a human decedent model. Am J Transplant 2022; 22:1037–1053. doi: 10.1111/ajt.16930
- 6.↑
Montgomery RA, et al. The decedent model: A new paradigm for de-risking high stakes clinical trials like xenotransplantation. Am J Transplant 2024; 24:526–532. doi: 10.1016/j.ajt.2024.01.035
- 7.↑
Massachusetts General Brigham. Massachusetts General Hospital performs second groundbreaking xenotransplant of genetically-edited pig kidney into living recipient. February 7, 2025. Accessed March 10, 2025. https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/mgh-performs-second-xenotransplant-of-genetically-edited-pig-kidney-into-living-recipient
