At the intersection of patient-centered care and disruptive science

There are over 80,000 people in the European Union with end stage renal disease (ESRD) who are waiting for a kidney transplant.¹ This life-saving procedure can offer improved survival, better quality of life, and significant healthcare costs savings due to long-term dialysis.

Non-profit organizations including Eurotransplant have been dedicated to ensuring fair and equitable allocation of organs by serving as a mediator between donor hospitals and transplant centers.  Playing an integral role in connecting key stakeholders throughout its network, Eurotransplant helps to facilitate the allocation and exchange of suitable organs for transplantation. 

In many instances, the efforts of Eurotransplant are helping to extend the lives of people with ESRD. However, for some patients with pre-formed antibodies called donor specific antibodies (DSAs) the wait for an organ can be excruciatingly long because of the complexity of their immunological profile. Considered highly sensitized, these patients spend longer than average time on transplant waiting lists waiting for a suitable donor – this can lead to an increase mortality risk.²

The complexity of highly sensitized patients in kidney transplantation

To transplant highly sensitized kidney patients waiting for an organ, desensitization needs to occur to ensure the body will accept the organ. Until 2020, there have been no clinical guidelines or consensus on desensitization in kidney transplantation.

Prof. Dr. Uwe.Heemann, Head of Department of Nephrology, Klinikum rechts der Isar der Technischen Universität, München, Germany: “Kidney transplantation is a life-saving opportunity for many kidney patients who need a suitable organ. And for highly sensitized patients, this is even more important as they tend to be some of the sickest patients. Innovative new approaches and guidelines to desensitization are a welcomed new way forward for clinicians and patients.”

Within the last 12 months the clinical community has recognized the importance of introducing new approaches to desensitization as evidenced by new clinical guidelines issued by the European Society for Transplantation (ESOT)³ and country-specific guidelines and consensus.

Vincenza Nigro, Franchise Lead, Kidney Transplantation, Hansa Biopharma said: “By advancing the science around desensitization, we are beginning to see transformative and disruptive approaches to transplantation care for highly sensitized patients. For those in the transplantation community, this is exciting progress for a group of patients with high unmet need.”

Ensuring equitable access to organ allocation for highly sensitized patients

With innovations in desensitization becoming more readily available and transplant centers gaining expertise and building infrastructure to navigate the complex nature of transplantation with highly sensitized patients, Hansa is excited to see that Eurotransplant is also reflecting the advancements being made in desensitization in its organ allocation approach.  

More than 30 years ago Eurotransplant created the Acceptable Mismatch (AM) program to increase transplantation for highly sensitized patients. To date, the program has helped more than 1,700 highly sensitized patients receive a kidney transplant.⁴

Recently the organization initiated an additional component to the AM program, the Desensitization Program – a first ever international allocation system utilizing imlifidase to enable kidney transplantation in highly sensitized patients with a very low chance of transplantation. To date, the Desensitization Program has identified 173 highly sensitized patients that have been on the wait list for more than 5 years. Centers in the Eurotransplant network are now able to offer these patients a transplant once a suitable organ is allocated.

Imlifidase is an antibody-cleaving enzyme originating from Streptococcus pyogenes that specifically targets and cleaves immunoglobulin G (IgG) antibodies and inhibits IgG-mediated immune response.⁵ It has a rapid onset of action, cleaving IgG-antibodies and inhibiting its activity within hours after administration. The efficacy and safety of imlifidase as a pre-transplant treatment to reduce donor-specific IgG was studied in four phase 2 open-label, single-arm, six-month clinical trials.^6-9

Prof. Dr. Sebastiaan Heidt, Head of Eurotransplant Reference Lab, said: “At Eurotransplant our commitment to facilitating equitable access to suitable organs is grounded in understanding and incorporating the latest innovations in patient care. The desensitization program using imlifidase has begun to identify its first patients and we are hopeful that we will begin to see imlifidase-enabled transplants in highly sensitized patients.”

While modernizing and standardizing clinical practice to reflect new approaches to care can take time, multi-stakeholder collaboration amongst industry, clinicians, non-profit organizations, and governments can speed innovative new approaches, drive better patient care and overall outcomes and clinicians can address the individualized immunological complexity of these individuals.

References

1. Newsletter Transplant 2020. pp 58–60.
2. Redfield R, et al. Nephrol Dial Transplant 2016; 31:1746–1753
3. European Guidelines for the Management of Kidney Transplant Patients with HLA antibodies. https://esot.org/wp-content/uploads/2022/07/WS06_Full-doc_07202022.pdf. Accessed on 20 October 2023
4. Heidt S, et al. Front. Immunol. 12:687254.
5. European Medicines Agency. Idefirix® summary of product characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/idefirix-epar-product-information_en.pdf. Last accessed: June 2023
6. Jordan SC, et al. N Engl J Med 2017; 377(5):442-453
7. Winstedt L, et al. PLoS One 2015; 10(7): e0132011
8. Lorant T, et al. Am J Transplant 2018;18(11):2752-2762.
9. Jordan SC, et al. Transplantation October 21 2020 - volume online first issue.