Pig-to-Human Organ Transplants Will Finally Begin Clinical Trials This Year todayheadline

Animal-to-Human Organ Transplants Hit Long-Awaited Testing Milestone

By Tanya Lewis edited by Dean Visser

The U.S. Food and Drug Administration recently approved the first-ever clinical trial of the transplantation of a nonhuman animal organ—a genetically modified pig kidney—into living human recipients. The study is set to begin by midyear and will initially involve six participants, but it could eventually include up to 50.

The study will allow researchers to evaluate the safety and efficacy of an approach to substituting pig kidneys for human ones in people who desperately need a transplant yet are either ineligible to receive a human kidney or unlikely to be offered one within five years.

“It is a very important milestone,” says Robert Montgomery, chair of the surgery department and director of the NYU Langone Transplant Institute, which he says is one of two sites for the study. A clinical trial “is the gold standard for assessing the safety and efficacy of a new drug or treatment.”

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More than 103,000 people in the U.S. are currently waiting for an organ transplant, and a shortage of donor organs means many will die before one becomes available. The idea of xenotransplants—operations to transplant organs from other animals into humans—has been around for at least a century. Early attempts used kidneys, livers and hearts from baboons, chimpanzees and other creatures. Most of these early experiments failed, in large part because the host’s immune system rejected the other species’ organ. But in recent years, big advances in genetic manipulation have revived xenotransplantation efforts.

Clinical trials are important because they have clear end points for data on safety and efficacy, as well as guidelines to establish who can participate and to ensure that any adverse events are reported. A handful of surgeries have been allowed outside of this framework, but these could only provide limited data compared with a formal trial.

In 2022 a patient named David Bennett became the first living person to receive a genetically modified pig heart transplant. A team at the University of Maryland School of Medicine performed the surgery using a kidney with 10 edits to its genetic code from a pig engineered by Revivicor (a subsidiary of United Therapeutics, the company providing the organs for the new trial). Sadly, Bennett developed complications and died two months later.

The following year, teams at NYU Langone Health and the University of Alabama at Birmingham transplanted single-gene-edited pig kidneys into human recipients who had undergone brain death but had some bodily systems artificially maintained for a short while. The recipients’ families had consented to let the scientists do so to study the organs’ function. Then, last March, Richard Slayman became the first living person to receive a modified pig kidney, one with 69 gene edits made by a company called eGenesis. Slayman, who was already seriously ill before the surgery, passed away nearly two months later. Two more genetically modified kidney xenotransplants have since been performed: Last year NYU Langone Health transplanted a pig kidney into a woman named Towana Looney, who is still doing well nearly three months later. And last week Tim Andrews, a patient at Massachusetts General Hospital, received a pig kidney made by eGenesis.

Some of these surgeries were approved under the FDA’s “expanded access” program, which allows very sick people to receive experimental treatments on a compassionate use basis. Others were part of a small pilot study of eGenesis pig organs that was greenlit by the FDA. But researchers had long awaited a full clinical trial, which would allow a broader and healthier range of individuals to be enrolled to better assess xenotransplant feasibility in a wider population.

The new trial will evaluate the rate of adverse events or death from any cause and the amount of protein in the urine (a sign of kidney malfunction)—as well as zoonotic infections (those carried by animals) and other infections—according to Dewey Steadman, head of investor relations at United Therapeutics. It is a combination phase 1-2-3 clinical trial, which means it will assess both safety and efficacy in a continuous manner. After the first transplant, there will be a 12-week waiting period. Once the first six patients have been transplanted for 12 weeks, an independent committee will evaluate the procedure’s safety and efficacy before expanding to a larger cohort of up to 50 people.

The kidney for each transplant—dubbed a “UKidney” by its makers—will come from pigs with 10 gene edits: six add human genes that make the organ more compatible with the human immune system, and four inactivate pig genes that can cause rejection or make the organ grow too large.

To qualify for the trial, participants must fit one of two criteria: either they must not qualify to be listed for a human kidney transplant, or they can be on the transplant list but unlikely to receive an organ—or likely to die before they do so—within five years. All participants will be 55 to 70 years old, have end-stage kidney disease and have been on dialysis for at least six months. They must also be free from other serious medical problems. In contrast, most of the people who have received a xenotransplant on a compassionate use basis have been severely ill, making it harder to assess the success of the transplant itself.

“This is the culmination of years of work with the FDA, who have been incredibly collaborative in this process,” Steadman says. “Both we and the FDA are really committed to bringing this [technology] to market to help patients who have no other options right now besides dialysis.”