The Business of Biofabrication

The field of organ transplantation is on the cusp of a advancement, with United Therapeutics (NASDAQ: UTHR) achieving a new milestone in xenotransplantation. The U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for its UKidney™ clinical trial, marking the first-ever human trial of a xenokidney designed for potential registration through a Biologics License Application (BLA). This groundbreaking development could offer a lifeline to thousands of end-stage renal disease (ESRD) patients who currently face long transplant waitlists and limited donor organ availability.

What is UKidney?

UKidney is an investigational xenokidney derived from a genetically modified pig with 10 gene edits. The modifications include:

• Six human genes added to improve immunological acceptance.
• Four porcine genes inactivated to reduce rejection risks and prevent excessive organ growth.

This gene-editing approach aims to create a transplantable organ that can function effectively in humans without the complications traditionally associated with xenotransplantation.

The Need for Xenotransplantation

The statistics surrounding ESRD are alarming. According to the American Kidney Fund:

• Over 557,000 patients in the U.S. rely on dialysis due to kidney failure.
• Only 21,000 deceased donor kidney transplants were performed in 2023.
• Many patients die while waiting for a donor kidney, particularly those aged 60 and older.

Xenotransplantation offers a potential alternative for patients who may not qualify for a traditional kidney transplant or are unlikely to receive a deceased donor kidney in time.

Clinical Trial Design

The UKidney trial is structured as a multicenter, open-label study designed to assess safety and efficacy. Unlike conventional trials that progress through separate Phase 1, 2, and 3 stages, this study follows a “phaseless” model, allowing for a streamlined evaluation of the therapy’s effectiveness.

Key trial details:

• Initial Cohort: Six ESRD patients will receive UKidney transplants at two centers, with a 12-week waiting period between the first and second transplants.
• Expanded Enrollment: If initial results are promising, the trial will expand to include up to 50 participants.
• Long-Term Monitoring: Participants will be followed for life to track kidney function, survival, and potential risks such as zoonotic infections.

Efficacy and Safety Endpoints

The trial will measure several key indicators to determine the success of UKidney transplants:

• Efficacy Metrics:
  • Patient survival rate and kidney survival rate at 24 weeks post-transplant.
  • Change in glomerular filtration rate (GFR), an essential marker of kidney function.
  • Quality of life improvements as measured by validated surveys.
• Safety Considerations:
  • Incidence of adverse events, including serious complications.
  • All-cause mortality.
  • Presence of proteinuria (excessive protein in urine) and risk of infections due to immunosuppression.

Implications for Bioprinting and Regenerative Medicine

While United Therapeutics is pioneering xenotransplantation, its work has significant implications for the broader field of regenerative medicine, including 3D bioprinting. Companies specializing in bioprinted tissues and organs are watching these developments closely, as success in xenotransplantation could accelerate research and regulatory pathways for lab-grown organs.

Xenotransplantation and bioprinting share a common goal: solving the organ shortage crisis. If UKidney demonstrates long-term success, it could pave the way for a hybrid approach where xenogeneic tissues are combined with bioprinted scaffolds, further enhancing compatibility and reducing rejection risks.

About United Therapuetics

United Therapeutics operates as a public benefit corporation (PBC), meaning it prioritizes both financial success and broader societal impact. The company’s mission is to leverage innovative technologies to expand the availability of transplantable organs, a commitment evident in its leadership role in xenotransplantation.

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