United Therapeutics’ Gene-Edited Kidney Xenotranspant UKidney Cleared for US Trial
The IND clearance constitutes the first for a xenokidney product.
United Therapeutics’ UKidney, an investigational gene-edited porcine kidney product intended to treat end-stage renal disease (ESRD) via xenotransplant, has received clearance of an investigational new drug (IND) application from the FDA.1
In light of the IND clearance, United Therapeutics intends to go forward with plans for a phase 1/2/3 clinical trial (NCT identifier pending) with the intention of supporting a biologics license application for the product. The trial will seek to recruit patients with ESRD who are ineligible for a conventional kidney transplant for medical reasons and patients with ESRD who are on a kidney transplant waitlist, but are unlikely to receive a conventional transplant within 5 years or are unlikely to survive until a human donor kidney is available. The trial is expected to perform its first xenotransplant around the middle of this year.
“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,” Leigh Peterson, PhD, the executive vice president of product development and xenotransplantation at United Therapeutics, said in a statement.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.”
UKidney consists of a porcine kidney that has 3 genetic edits intended to inactivate genes related to organ rejection in humans and 1 genetic edit intended to inactivate a gene that can cause organ growth. It also consists of the addition of 6 human genes intended to make way for immunological acceptance and compatibility in human patients.
The multicenter, open-label, will follow patients for a 24-month posttransplant period, and then continue to follow patients for life afterwards. End points for the trial include patient survival rate, UKidney survival rate, the change in the measured glomerular filtration rate, and the change in the quality of life in participants, as assessed at 24 weeks posttransplant. Overall survival time of both patients and UKidneys will also be evaluated. With regard to safety, end points will include the incidence of adverse events (AEs) and serious AEs; all-cause mortality; and the incidence of proteinuria, zoonotic infections, and opportunistic infections.
“Eliminating the need for dialysis or limiting time on dialysis may improve survival for many patients with ESRD,” Noah Byrd, PhD, RAC, the vice president of global regulatory affairs at United Therapeutics, added to the statement.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.”
According to clinicaltrials.gov, a phase 1 clinical trial (NCT05340426) for a product referred to as UKidney was previously registered on the website by sponsor University of Alabama at Birmingham. Although the trial, which had an estimated start date of January 31, 2024, was withdrawn without enrolling a single patient. The reason for withdrawal states that approval for the trial was not granted by government bodies.
UKidney is not the only gene-edited porcine kidney product currently in-development for kidney disease.2 In September 2024, eGenesis garnered $191 million in a round of Series D financing for EGEN-2784, a porcine kidney that features a number of genetic modifications intended to prevent rejection after transplant into human patients. The funds were raised following the company's performance of the first successful xenotransplant of a porcine kidney into a human patient, which was carried out under the FDA's Expanded Access pathway, earlier that year. EGEN-2784 includes gene edits intended to knock out 3 genes involved in the synthesis of glycan antigens believed to be related to hyperacute rejection. It also includes the addition of 7 human genes related to modulation of rejection.
“Decades of progress in cross-species transplantation, accelerated by the evolution of modern genome editing tools and next-generation sequencing, have enabled eGenesis to advance genetically engineered organs to the clinical setting,” Peter Hebert, cofounder and managing partner of investor Lux Capital, said in a September 2024 statement.2 “What was once science fiction is now science fact. We are thrilled to support eGenesis in advancing this pivotal modality to address one of the most intractable challenges facing medicine today – the global organ shortage crisis.”
