David-Alexandre C. Gros, MD, CEO of Eledon Pharmaceuticals, is overjoyed to learn that the second patient to receive a genetically modified pig kidney developed by eGenesis has been released from the Mass General Hospital (MGH) Transplant Center.
“The patient’s latest creatinine, which measures how well the organ works, is at 1, essentially normal,” Gros told Inside Precision Medicine. “This is someone that went from being on dialysis with low chances of being able to get a kidney, having essentially no kidney function, to in a week or two having normal kidney function—it’s remarkable!”
The patient was released in part because of Eledon’s investigational anti-CD40L antibody, Tegoprubart, which is being used as a key part of the immunosuppression therapy regimen in the patient who had a xenotransplantation of a kidney on January 25, 2025.
The news coincided with the publication of a New England Journal of Medicine article from eGenesis, Eledon, and MGH detailing the autopsy of the first patient to receive a pig-to-human kidney xenotransplant on March 16, 2024, which also took place at MGH. According to the report, the xenograft functioned immediately, as evidenced by a rapid and progressive decrease in creatinine levels, and dialysis was no longer required. However, despite continued kidney function, the patient died from unexpected, sudden cardiac causes. The autopsy revealed severe coronary artery disease and ventricular scarring without evident xenograft rejection.
“[The first pig-to-human kidney xenotransplantation patient] had been seen in the clinic that morning before he passed,” Gros explained. “He was fine, and later on that day, he had a cardiac event. The autopsy showed that the kidney was fine.”
While this reinforces the significant progress made in kidney xenotransplantation, to Gros, it’s been a long time coming.
“The problem is that in the United States, average survival on dialysis is less than five years,” said Gros. “People don’t realize that we do better with most cancers at keeping people alive than we do on dialysis. So when you’re on dialysis for a few years, if you don’t have a living donor and it’s not looking like you’re doing that well, then you’re not going to get a human organ.”
The crux of kidney transplants
For Gros, the organ transplant shortage problem has two key components. If a patient is in good enough health to stay on the transplant list and, often after a long wait, is fortunate enough to receive a kidney transplant, these donor organs typically last about 10–15 years. This may not be a huge issue for older patients. However, the average age of patients who receive kidney transplants is around 50 years old, which means that there are patients in their 20s and 30s on the kidney transplant list.
“To have a normal lifespan of 80 in the United States, you’re going to need multiple organ transplants,” said Gros. “But we don’t have enough organs. If we can extend the functional life of organs, that will help alleviate the shortage and have fewer repeats. We aim to achieve that through the public release of our clinical trials on human-to-human transplants.”
The second component has to do with supply—there aren’t enough organs to go around for the people who qualify for a human organ transplant, let alone for those who do not. People with end-stage kidney disease and other medical problems who can’t get a human organ only have dialysis as an option. It’s expensive (an average of almost $100,000 a year per patient), painful, and takes time. In theory, xenotransplantation could provide a significant uptick in the supply of organs. So, both human-to-human and pig-to-human kidney transplants would greatly benefit from an extended expiration date.
Lifelong immunosuppression
One of the key variables in maintaining healthy transplants, whether from humans or pigs, is keeping graft-versus-host disease (GVHD) in check, which is what led Eledon to develop the immunosuppressant Tegoprubart.
“The immune system will always remain active [post-transplant],” said Gros. “As a result, the immune system needs to be modulated for the lifespan of the organ. If they stop immune treatment, the immune system will come back and attack immediately, attacking and destroying the organ. That’s true with both human-to-human as well as pig-to-human organs. So [transplant recipients] are on multiple drugs for life.”
Eledon is currently running a Phase Ib trial (NCT05027906), a Phase II trial (BESTOW; NCT05983770), and a long-term safety and efficacy extension study (NCT06126380) to test Tegoprubart as a way to keep kidney transplant recipients from rejecting their new organ. In June 2024, Gros and his team presented data from the 13 participants in the ongoing Phase Ib trial supporting Tegoprubart’s potential to protect organ function in patients undergoing kidney transplantation. Results demonstrated that Tegoprubart is generally safe and well tolerated in patients undergoing de novo kidney transplantation.
Data is a bit harder to come by for the xenotransplantation side of things, which is why the news of the second pig-to-human kidney transplant being released from the hospital is a significant boon for Eledon, eGenesis, and the team at MGH.
“The data is real-time with the xenotransplantations,” said Gros. “We’ve had multiple people with kidney xenotransplants go home, so I don’t think this is a dream anymore. It doesn’t mean it will work, but it might work.”
The future of xenotransplantation
In addition to the kidney, two xenotransplantations have been done with genetically engineered pig hearts. While the cardiac xenotransplant field has been slightly ahead, with the second pig-to-human heart operation in 2023, Gros expects to see bigger gains on the kidney side, followed by the liver xenotransplantation space.
Gros explained, “It’s harder with hearts. If a kidney stops working, their fail-safes are things you can’t do with a heart. It’s tougher, but we’re seeing advancements. We’ll also see advances in the liver with xenotransplantation. That might be livers kept outside of the human body and attached to the humans while remaining outside of the body. Those will be the three areas where you see xenotransplantation advances coming up.”
So far, a limited number of gene-edited pig kidney transplants have previously taken place under the FDA’s compassionate use program, allowing investigational medical products to be used outside clinical trials when a patient has a life-threatening condition. Last week, United Therapeutics and eGenesis received approval from the FDA to conduct clinical trials transplanting genetically modified pig kidneys into patients with kidney failure.
