FDA greenlights trial of gene-edited pig kidneys as treatment for end-stage kidney disease

It’s been almost three months, and Stewart is home, back to work, and has even been able to go e-biking on a lakeside trail with his wife, blessedly untethered to the grueling schedules of dialysis for the first time in years, all thanks to a gene-edited Yucatan miniature pig named Lavender.

Stewart is the most recent recipient of a pig kidney — but chances are, he won’t hold that distinction for long. On Monday, eGenesis, a Cambridge-based biotechnology company, announced that it had been cleared by the Food and Drug Administration to begin a trial of kidneys from donor pigs that have been CRISPR’d to make their organs more human-friendly. Now, Massachusetts researchers will be performing more surgeries like Stewart’s to see whether these animal parts could serve as a lifeline for people with end-stage renal disease.

It’s the latest advance in a scientific swine race some hope might solve America’s organ shortage. In the US, about 13 people die each day waiting on transplant lists for human organs that are in scarce supply and aren’t equitably distributed. A few US companies are neck-and-neck in their attempts to use pig parts instead. eGenesis was co-founded by renowned Harvard bioengineer George Church and one of his protégés, Luhan Yang, whose breakthroughs in using CRISPR to produce animals with more and more complicated edits have reinvigorated the long-sputtering field of xenotransplantation.

Meanwhile, Revivicor, a subsidiary of Maryland-based United Therapeutics, has been trying its own porcine organs — including the first pig-to human heart and kidney transplants — from animals with fewer genetic modifications. In February, United Therapeutics got the okay from the FDA to begin a clinical trial of its so-called “UKidney.” A spokesperson told STAT the company is “at least a month away” from performing the first transplant of the trial.

Until now, these experiments have proceeded through an expanded access program at the FDA, in which patients with life-threatening conditions can gain access to unapproved therapies on a case-by-case basis.

For the patients involved, their fellow pig-organ recipients can be both a source of support and apprehension. Before he got his transplant, Tim Andrews of Concord, N.H., went on Facebook to connect with Towana Looney, who at that point was the person who’d had a pig kidney in her body the longest.

“They were a little nervous at Mass General, because this stuff is all secret-secret,” Andrews told STAT. “But I said, ‘Listen, guys, you’re about to put something into me that only one other person on the planet currently has. I’d like to know how she feels.’” They began to exchange messages, and in Jan. 2025, Andrews had the surgery himself.

In April, he was back in the hospital with a complication when he heard that Looney’s pig kidney had failed. Months after she received the organ in Nov. 2024, Looney’s immune system started attacking it, and her medical team decided the best course of action was to remove it. “I was scared,” Andrews said. “That was the first time in this whole thing that I really got a little concerned.”

He knew he had eGenesis’ pig kidney, and she had Revivicor’s, but even so, she was the closest precedent he had. “But the doctors said, ‘Don’t worry about it. You have a better pig than her.’ I thought they were joking at first, but I truly do have a better pig.”

(Leonardo Riella, Massachusetts General Hospital’s medical director of kidney transplantation, said that Looney’s kidney’s failure was a “devastating moment” and that a number of factors can influence an operation’s success, including the recipient’s underlying health and the anti-rejection medications used, as well as the pig’s gene-edits and other traits. To him, having more than one company raising donor pigs means the field advances faster, everyone learning from each case. Looney went back on dialysis and has begun to recover her health.)

The idea behind xenotransplantation first emerged more than a century ago. But turning it into reality requires overcoming the millions of years of divergent evolution that has made the human body hostile to organs grown inside a pig. Only in the past decade have scientists developed DNA-altering tools sophisticated enough to outfit organs from other species with genetic tricks for evading the human immune system.

Both Revivcor and eGenesis have landed on some of the same alterations — like disrupting genes that code for antibody-activating sugars studding the surface of pig cells or adding human genes that control inflammation and clotting — to cloak their organs from the many layers of immune defenses the human body can mount. In experiments in baboons published in 2023, eGenesis also showed it had found a way to keep its pig kidneys expressing the human transgenes for up to two years, overcoming a tendency for the new genetic material to get silenced over time.

The team at eGenesis has gone one step further, using CRISPR to snip dozens of potentially dangerous-to-humans viruses out of the pig genome, resulting in animals incapable of infecting anyone receiving one of their organs. The changes are intended to address one of the unique concerns that come with cross-species organ transplant: the risk of transmitting animal diseases to humans. After the recipient of Revivicor’s first pig heart passed away, the University of Maryland research team that performed the procedure reported that the organ had developed a latent viral infection, despite its donor animal being raised in a pathogen-free facility and testing negative for the virus prior to transplant. Although there was no evidence the virus transmitted to the patient, the researchers concluded it likely contributed to the failure of the organ and raised concerns about the possibility of zoonotic spillover.

United Therapeutics, which declined to comment for this story, did not disclose which hospitals it’s working with for the trial. According to clinicaltrials.gov, the principal investigator is NYU Langone’s Robert Montgomery, who performed the world’s first kidney xenotransplant into a deceased patient. The study will focus on patients who have been determined ineligible to receive a kidney from a human donor for medical reasons, or who are on a waitlist but deemed more likely to die than receive an organ within five years. Researchers will initially dose six patients with end-stage renal disease, and after all six have been followed for at least 12 weeks, United plans to expand the trial up to 50 patients. It’s designed to look primarily at how patients fare after six months, tracking measures such as patient survival, kidney function, and infections, but patients will all be followed for the rest of their lives.

Mike Curtis, president and CEO of eGenesis, told STAT that his company’s trial will have a similar design — initially enrolling three patients who will receive transplants at Massachusetts General Hospital before expanding to 30 patients at additional trial sites. The current series, which includes Andrews and Stewart, is a course-correct of sorts, after MGH’s first pig kidney transplant in 2024.

In that case, the patient had spent a number of years on dialysis and ended up dying of an “unexpected cardiac event” about two months after receiving his xenotransplant. For this expanded-access study, Riella said, “instead of getting very sick patients who unfortunately had a low chance of making it the next couple months if something didn’t change, or if they didn’t get a kidney transplant, we were trying to get patients early in their journey, before dialysis has caused all its wear and tear,” adding, “We want to try to remove any confounding factors that would prevent us from having the right interpretation of what’s happening after that kidney transplant.”

About the upcoming trial, Curtis said he and his team “were thrilled” the FDA had agreed to a primary endpoint of organ function at six months. “That’s clinically meaningful to patients that are on chronic dialysis,” he said. “Mr. Andrews has already passed that. Getting him off of dialysis for eight months has been life changing.”

When Stewart’s chronic hypertension devolved into kidney disease a few years ago and a doctor put him on dialysis, he wondered how he was going to fit it in. His life was fairly full already. He had two kids, was married and worked two full-time jobs, one at a nonprofit program through which people with disabilities travel around the country for adaptive lacrosse and power-chair soccer matches, the other at a sports medicine program. (Mass General Brigham purchased the sports medicine program a little over a year ago, making Stewart an employee.) Where was he going to find time for three appointments a week, lasting four or five hours each, so that the toxins normally filtered out by his kidneys could instead be dealt with by a machine?

“I was going in 4:30, 5 o’clock in the evening, staying close to 10 at night,” he said.

He learned about the possibility of xenotransplantation by chance. He was at one of those dialysis appointments in Dover when the staff mentioned that a patient of theirs in Concord no longer needed to come in: He was the proud recipient of a pig kidney. As renal disease patients go, Stewart was fairly healthy. Maybe he’d be a good candidate.

He put his name down that same night. His motivation was partially altruistic. He knew there were tens of thousands of Americans on the kidney transplant list, many of whom would die waiting. Nudging pig-organs toward mainstream use could help save lives.

But Stewart wanted this for himself, too.

Dialysis can be a kind of hell — both prolonging your life and forcing you to wonder whether you’re living much at all. It isn’t just the time commitment. It’s also a poor replacement, wearing you down while providing only about a tenth of the function a healthy kidney would. Plus, it’s intermittent: no match for the toxins and minerals a body produces continuously and needs to excrete. Those start to build up, causing inflammation. Blood vessels calcify and harden. The heart works extra hard to push fluid through canals now constricted. Cardiac muscle begins scarring. Risks of arrhythmia and heart attack increase.

“I’m sitting in this chair, four, five hours a day, every other day, waiting to die,” Andrews said of his few years on dialysis. “I can’t walk, I can’t do this, I can’t do that. All I want to do is throw up and go to sleep.”

When he heard about Andrews’ xenotransplant, Stewart knew his prospects weren’t great. If he waited for a deceased donor, it could be three to five more years. By that time, his thrice-weekly appointments would have taken their toll. “Oftentimes people start dialysis, and they’re good candidates for a transplant, but by the time they get to that spot in the list where their name comes up, their health has declined to the point where they’re no longer eligible,” Stewart said.

He had no fewer than eight people offer to donate one of their kidneys: his sister, his brother, people he knew from work, one friend he’d made in first grade, another from the University of New Hampshire who’d moved to West Virginia and hadn’t been in touch since their graduation in 1993. But none made it through the screening process, for reasons of blood type or hypertension or psychological risk.

A pig might just be his best shot.

Andrews’ case has been a source of hope in the xenotransplantation world. “Having a patient now off dialysis for seven months, and having all the minerals and the fluid balance perfectly, regulated as it would be by a human kidney, is incredible,” Riella said. “It’s been mind-blowing to review his blood work.”

That success so far doesn’t mean it’s been easy for Andrews. At one point, his body began rejecting the new organ. At another, he had an infection. At yet another, there was a bleed following a biopsy, the blood putting pressure on the kidney; he had to undergo a surgery during which he was awake, pointing into his opened abdomen — “like raw hamburger,” he said — telling Riella where it hurt so that the doctor could siphon stuff out from the right spots.

Andrews initially called his kidney Wilbur, after the piglet in “Charlotte’s Web,” but when he found out all of eGenesis’ pigs were female, he renamed it Wilma. He invokes it, almost like a trusted friend, when thinking about the uncertainty he’s signed up for: “Tomorrow could be the end. Any day, Wilma could quit. Now, she’s a champion, and has carried on through all of this stuff that’s happened. But there’s no guarantee.”

The long recovery — and the arduous caregiving it has required — eventually put a strain on his marriage. In the last few months, after decades together, Andrews and his wife parted ways. “It just became too much. It wasn’t like, ‘I don’t like you anymore.’ It was, ‘I can’t handle this, you go into the hospital just for a blood test and you’re gone for three weeks, then you come home and can’t even pick up a gallon of milk,’” he said. He’s now living with his sister, a retired nurse, whose training makes it easier to help, and he takes every chance he gets to talk about the need to support not just patients, but their caregivers, too.

Stewart, too, has had side effects similar to the ones he might experience if he’d gotten a human kidney. Anti-rejection medications can impede insulin’s ability to process sugars, and he’s developed diabetes. His ankles are sometimes swollen to the size of softballs. There’s plenty he’s not back to yet. He’s not about to get behind a boat on water skis, or lower himself into a kayak, or swim in the ocean; he doesn’t have the energy for hiking.

Yet when he isn’t at his myriad follow-up appointments, he’s at his house, with nautical etchings on the walls and pinkish conch-shells in the bathroom; he’s taking New England trips with his wife, a kindergarten teacher who insists the kids always get crazy when there’s a full moon; he’s stroking his mutt Casco, marveling that a creature that sheds so much still has any fur to stroke.

It sure beats being back on dialysis.