The U.S. Food and Drug Administration (FDA) has greenlit clinical trials for two biotechnology firms, United Therapeutics and eGenesis, to conduct groundbreaking research involving the transplantation of genetically modified pig kidneys into individuals suffering from kidney failure. This marks a significant stride towards addressing the critical shortage of human organs available for transplantation.
Trial Designs and Objectives
United Therapeutics is set to initiate its trial in mid-2025, beginning with an initial cohort of six patients diagnosed with end-stage renal disease. These patients have been undergoing dialysis for a minimum of six months and are otherwise in stable health. The study may eventually expand to include up to 50 participants. According to the company's statement, the patients will receive the company’s UKidney, followed by a 24-week post-transplant period that will include a safety assessment. Participants will then be tracked for the rest of their lives in order to determine survival, kidney function and other factors.
Meanwhile, eGenesis has received FDA approval to commence a separate kidney transplant study involving three patients. According to The New York Times, doctors will monitor each transplant patient for 24 weeks and require lifelong follow-ups to track health outcomes and potential risks such as pathogens that could cross from pigs to humans.
Mike Curtis, president and chief executive of eGenesis, hailed the approval as a "transformative era in organ transplantation."
Addressing the Organ Shortage
The impetus behind these trials lies in the severe disparity between the demand for and the availability of donor kidneys. In the United States alone, over 550,000 individuals are grappling with kidney failure, with nearly 100,000 patients on the transplant waiting list. However, in 2023, fewer than 25,000 kidney transplants were performed, leaving countless patients to endure years of waiting or, tragically, succumb to their condition before receiving a donor organ.
Genetic Modifications and Compatibility
To mitigate the risk of organ rejection and enhance compatibility with the human immune system, both United Therapeutics and eGenesis have undertaken extensive genetic modifications of pig genes. United Therapeutics' pigs have undergone 10 gene edits, incorporating six human genes and removing four porcine genes associated with rejection. eGenesis has employed a more extensive approach, implementing 69 gene edits, primarily aimed at inactivating viruses that could potentially pose a threat to human recipients.
Ethical and Safety Considerations
While the potential benefits of cross-species transplantation are undeniable, ethical and safety concerns persist within the medical community. One primary apprehension revolves around the possibility of zoonotic infections, wherein pathogens could jump from pigs to humans. Despite both companies adhering to stringent biosecurity protocols and conducting regular screenings for pathogens, the risk remains a subject of ongoing scrutiny.
Christopher Bobier, an associate professor specializing in bioethics and health policy at Central Michigan University College of Medicine, voiced concerns about the potential for recipients to become infected with undetected pathogens from the porcine source. Additionally, questions have been raised regarding the capacity of patients to provide truly informed consent, given the challenging circumstances faced by individuals on dialysis.
Trial Timelines and Future Prospects
United Therapeutics anticipates commencing transplants by mid-2025, with a few months between procedures to assess each outcome before moving forward. eGenesis plans to wait six months between its first two patients, then three months before transplanting a third.
Even if these trials yield positive outcomes, uncertainties remain regarding the cost of pig organ transplants and the extent to which insurance coverage will be provided. Nevertheless, these clinical trials represent a pivotal step forward in the field of xenotransplantation, offering hope for a future where the organ shortage crisis may be alleviated through innovative medical advancements.
