Xenotransplantation and Future Equitable Access

Disparities exist in access to transplantation globally. Less than 1% of worldwide transplants are performed in low-income nations annually. It has been hypothesized that in low- and middle-income countries (LMICs) with transplantation capabilities, the major hurdles to performing more transplantations are procurement, focused on (a) logistical elements (eg, timely transport of organ) rather than infrastructure (eg, transplant surgeons; patient care abilities) ¹ and (b) scarcity of deceased donors. ² There is great need for deceased donor transplant in many LMICs as, for instance, much of the global burden of chronic kidney disease occurs there. ³

Xenotransplantation presents the potential to alleviate allotransplant waitlists and the scarcity of deceased donors by providing greater numbers of transplantable organs that could be readily available for transplant. Clinical trials appear likely to begin soon, with many decedent studies having been performed and 2 cardiac xenotransplantations that took place in 2022 and 2023.

In 2008, the First World Health Organization (WHO) Global Consultation on Regulatory Requirements for Xenotransplantation Clinical Trials met in Changsha, China, resulting in the Changsha Communiqué. This document outlines principles on ethics, public health, and recommendations for the WHO, Member States, and investigators. Despite significant progress in xenotransplantation since its publication, one overlooked aspect of the Changsha Communiqué is Principle 10, which states “consideration should be given from the beginning to future equitable access to this therapy” (p. 2). ⁴ This principle was reaffirmed by WHO in 2011 and 2018 at subsequent global consultations that were held in collaboration with the International Xenotransplantation Association, an official section of The Transplantation Society. Yet, determining what future equitable access to xenotransplantation, should it prove to be a safe and effective alternative to allotransplantation, means in practice is undefined. To address global transplantation disparities, detailed clarification is needed, as currently Principle 10 is impracticable without further defining.

A conclusive definition of equitable access is elusive, but prior WHO publications provide insight. In 1997, the WHO stated equitable access “means that essential drugs, when needed, are available to and affordable by all” (p. 8). ⁵ This aspiration is unrealized with essential medicines, leaving around 2 billion people lacking access due to unavailability and unaffordability. Essential medicines, many delivered by mouth, are exceedingly easier to provide a patient than a transplantation; hence, meeting the standard envisioned by WHO for xenotransplantation is challenging.

Nonetheless, progress is possible. Although the Changsha Communiqué lacks legal binding, its ethical influence, due to the WHO's global prominence, holds significant weight. Presently, biotechnology companies predominantly fund xenotransplantation research. Hence, any vision of future equitable access must involve these companies, urging them to integrate equitable access into their corporate social responsibility. Strategies may include pricing regulations and subsidies for those in need, reducing financial barriers to access. Initiating conversations with these companies and stakeholders, including Member States, is a crucial first step. Discussions should include scaling up production of pigs to meet the shortage of organs, plans for opening markets in LMICs so that xenografts can be procured near the transplant site, and associated costs.

Whether xenotransplantation will be a safe, effective alternative to allotransplantation is still uncertain. However, with xenotransplantation advancing, and given Principle 10, action needs to occur if this remains a WHO commitment and so that the current disparities in access globally are not further perpetuated.