FDA Clears First Xenotransplant Trial for Gene-Edited Kidneys

The US Food and Drug Administration has cleared United Therapeutics’ Investigational New Drug application to initiate a clinical study of the company’s investigational UKidney™ derived from a 10 gene-edited source pig.1

According to a February 3, 2025, press release from the company, the study will enroll an initial cohort of 6 patients with end-stage renal disease (ESRD), expanding to up to 50 participants, and is intended to support a Biologics License Application with the FDA. The first xenotransplant in the trial is expected to be performed around mid-year 2025.1

“Clearance of our IND for this first-ever clinical trial of a xenokidney represents a significant step forward in our relentless mission to expand the availability of transplantable organs,” said Leigh Peterson, PhD, executive vice president of product development and xenotransplantation at United Therapeutics.1 “Our goal is to increase the availability of transplantable organs to offer a therapeutic alternative to a lifetime on dialysis for a large population of patients who are unlikely to receive an allogeneic kidney transplant.”

According to data from the Organ Procurement and Transplantation Network, more than 100,000 people in the US are currently on the national transplant waitlist, with another person added every 8 minutes. In 2023, more than 27,000 kidney transplants were performed, and nearly 90,000 people are still seeking a kidney transplant as of September 2024. With the number of patients seeking a transplant far exceeding the number of donor kidneys available, the US currently faces a major public health crisis.2

In March 2024, a group of Harvard Medical School physician-scientists at Massachusetts General Hospital transplanted a genetically edited pig kidney into a 62-year-old human patient with type 2 diabetes and high blood pressure. The kidney used in the surgery was provided by eGenesis and had 69 genomic edits to remove certain pig genes that produce sugars with antibodies human immune systems react to; add certain human genes to improve the kidney’s compatibility with humans; and inactivate viruses present in all pig genomes, known as porcine endogenous retroviruses, in the donor pig to eliminate risk of infection in the recipient.3

The first-of-its-kind medical procedure was conducted under a single FDA Expanded Access Protocol. Although surgeons had indicated they believed the pig kidney would last for at least 2 years, the patient died after just 2 months.3,4

Now, United Therapeutics seeks to expand xenotransplant research with a first-in-human clinical study aiming to assess the safety and efficacy of the UKidney in 2 groups of participants:

• ESRD patients who have been assessed and determined to be ineligible for a conventional allogeneic kidney transplant for medical reasons.
• ESRD patients who have been on the kidney transplant waitlist but are more likely to die or go untransplanted than receive a deceased donor kidney transplant within 5 years.

“Eliminating the need for dialysis or limiting time on dialysis may improve survival for many patients with ESRD,” said Noah Byrd, PhD, RAC, vice president of global regulatory affairs at United Therapeutics.1 “We appreciate the productive collaboration with the FDA in advancing our efforts to bring this potentially revolutionary therapeutic option to the hundreds of thousands of ESRD patients.”

References

1. Businesswire. United Therapeutics Corporation Announces FDA Clearance of its Investigational New Drug Application for the UKidney Xenotransplantation Clinical Trial. February 3, 2025. Accessed February 3, 2025. https://www.businesswire.com/news/home/20250203431557/en/United-Therapeutics-Corporation-Announces-FDA-Clearance-of-its-Investigational-New-Drug-Application-for-the-UKidney-Xenotransplantation-Clinical-Trial
2. HRSA. Organ Donation Statistics. October 2024. Accessed February 3, 2025. https://www.organdonor.gov/learn/organ-donation-statistics
3. Mass General Brigham Communications. In a First, Genetically Edited Pig Kidney Is Transplanted Into Human. Harvard Medical School. March 21, 2024. Accessed February 3, 2025. https://hms.harvard.edu/news/first-genetically-edited-pig-kidney-transplanted-human
4. The Guardian. Pig kidney ‘xenotransplant’ patient dies two months later. May 11, 2024. Accessed February 3, 2025. https://www.theguardian.com/science/article/2024/may/12/pig-kidney-xenotransplant-patient-dies-two-months-later