Full Press Release Details
CytoSorb with Ex Vivo Organ Perfusion: Transforming the Future
of Solid Organ Transplantation
human retrospective study, CytoSorb and ex vivo lung perfusion prior to lung transplant increased in-hospital and one-year survival
N.J., September 11, 2023 - CytoSorbents Corporation (NASDAQ: CTSO), a leader
in the treatment of life-threatening conditions in intensive care and cardiac surgery using blood purification via its proprietary polymer
adsorption technology, highlights the growing momentum of ex vivo organ perfusion in organ transplantation and the vital role
CytoSorb and ECOS-300CY are playing in this burgeoning field. In particular, these technologies may help to improve the quality
and number of usable organs while improving transplant success rates. Importantly, data from recent peer-reviewed publications highlight
how these innovative therapies may improve outcomes in the specific field of lung transplantation.
- Organ Transplantation, Ex Vivo Organ Perfusion, and CytoSorb/ECOS-300CY
transplantation is the gold standard treatment for end-stage organ failure. However, suitable donor organs are scarce and many patients
often die waiting for an organ to become available. According to the Global Observatory on Donation
and Transplantation, there were approximately 158,000 solid organ transplants in 2022 globally. According to the United Network
of Organ Sharing (UNOS) and the European Directorate for the Quality of Medicine and Healthcare (EDQM), in 2022 in the U.S.
and E.U. alone, there were approximately an equal number of patients, roughly 153,000, on the transplantation waitlist, primarily due
to the lack of suitable organs. Every 10 minutes, someone is added to the waitlist, and roughly every half hour, someone dies on the
waiting list, waiting for an organ that never comes.
vast majority of donated organs are from deceased donors, often due to irreversible cardiac or brain death. However, due to a variety
of factors, including ischemia and reperfusion injury, cold storage, and the manner by which the donor died, these organs are often damaged
with significant inflammation, jeopardizing organ health and importantly the success of the transplantation. In the U.S., according
to a 2020 Millman research report, a single lung transplant costs approximately $930,000, a two lung transplant: $1.3 million, a
kidney transplant: $443,000, a liver transplant: $878,000, and a heart transplant: $1.7 million. Due to the expense of failure, many
organs are discarded, despite the significant need. In addition, many organs, despite being deemed transplantable, develop problems of
delayed graft function or primary graft dysfunction after surgery. This is different from organ rejection and can happen with any organ.
For example, in lung transplantation, the rates of potentially life-threatening lung failure within the first several days after transplant,
called severe primary graft dysfunction (PGD), can be as high as 30%, resulting in high 90-day (20-25%) and 1-year (30-35%) mortality,
which is 3-5 times higher than if PGD did not occur. Strategies that can improve the health of organs or improve postoperative outcomes
are key to the future of solid organ transplant.
vivo organ perfusion is an increasingly used strategy to preserve and potentially improve the
functioning of lungs, hearts, livers and kidneys following organ harvest and during transport by reducing ischemic, reperfusion, and
cold storage injuries caused by conventional static cold storage. It also has the potential to increase the available donor pool of organs
by salvaging substandard ones that would otherwise be discarded. Ex vivo perfusion circulates temperature controlled, oxygenated,
nutrient rich fluid or blood products through the organ to improve its viability. However, ex vivo perfusion does not adequately
address the ongoing release of cytokines and other inflammatory mediators generated by the damaged organ that cause ongoing injury and
compromised function. Based on recent data, we believe the integration of our cytokine adsorptive technologies (i.e. CytoSorb, ECOS-300CY)
with ex vivo organ perfusion has the potential to transform the field of organ transplantation by not only elevating organ preservation
and rehabilitation to a new level, but by improving clinical outcomes after the surgery. The combination has been used successfully in
heart, liver, and kidney transplants to date, but the largest body of data comes from lung transplantation.
and ECOS-300CY in Lung Transplantation
final analysis of the U.S. CytoSorb Therapy in COVID-19 (CTC) Registry was published recently
in the journal Critical Care and demonstrated that the combination of CytoSorb and extracorporeal membrane oxygenation (ECMO)
therapy resulted in 74% 90-day survival in 100 critically ill patients from 5 major U.S. ECMO centers who had COVID-19 with severe acute
respiratory distress syndrome (ARDS) and who failed mechanical ventilation. This compared favorably to the 52% 90-day survival rate reported
by the Extracorporeal Life Support Organization (ELSO) in over 15,000 comparably ill COVID-19 patients using ECMO alone. The paper highlighted
the concept of "enhanced lung rest," where CytoSorb is used to remove circulating inflammatory cytokines and toxins that
can cause or worsen lung injury via capillary leak syndrome, pulmonary edema (i.e. fluid in the lungs), and severe inflammation. The
ultimate goal of CytoSorb therapy is to help stop severe inflammation and promote lung healing and recovery.
lung rest" concept has carried over to lung transplant, where inflammation in donated lungs causes the same capillary leak syndrome,
pulmonary edema, and compromised lung function, and is a major contributor to primary graft dysfunction (PGD), as mentioned earlier.
2017, Iskender and Inci, et al., from University Hospital Zurich in Switzerland, published
the first study in the Journal of Heart and Lung Transplantation using CytoSorb with ex vivo lung perfusion (EVLP) in a controlled
pig lung model, demonstrating decreased circulating cytokines, decreased microscopic lung injury, improved electrolyte balance, and improved
lung mechanics with easier ventilation of the lung. In 2021, the team published a follow-up study in the Journal of Heart and Lung
Transplantation where they took the model to the next step by transplanting the EVLP-treated lungs (with or without CytoSorb) into
pig recipients. They found that EVLP with CytoSorb significantly improved the functioning of the transplanted lung from both a mechanics
and gas exchange standpoint.
the 2022 landmark paper published in the prestigious journal Nature Communications, Ghaidan
and Lindstedt, et. al., studied the impact of CytoSorb and EVLP in a pig lung transplantation model. Lung injury and ARDS were induced
in pig donors by endotoxin injection. Once harvested, these compromised lungs all underwent EVLP and single lung transplantation into
a new pig recipient. The study was divided into three groups. The "untreated" group did not have CytoSorb at any time.
The "treated" group was subdivided into a) the "One-step" group that did not receive CytoSorb during EVLP
but received CytoSorb postoperatively following lung transplant, and b) the "Two-step" group had CytoSorb both during
EVLP, and then again postoperatively following lung transplant. In a detailed and well-controlled study, the researchers followed many
parameters, including cytokines and inflammatory cells in the blood and lung, level of lung inflammation, changes in histopathology and
gross pathology in the lungs, and many clinical parameters including recovery of lung function, oxygenation, hemodynamic stability, and
development of severe (Grade 3) primary graft dysfunction (PGD). Importantly, the rates of PGD in the first 72 hours after transplantation,
which directly correlates with risk of death, were much lower when CytoSorb was used. Researchers noted that 83% (5/6) in the Two-Step
group, and 50% (2/4) in the One-Step group had no PGD at all, compared to the 83% (5/6) in the non-treated group that developed Grade
3 severe PGD. Overall, researchers concluded that the use of CytoSorb both during EVLP and in the recipient after transplantation was
superior in virtually all respects compared to not using it at all, or using it only after transplantation. They concluded that the use
of CytoSorb in this model has been shown to:
inflammation and restore pulmonary function during EVLP, (ii) restore function and decrease inflammation following transplantation,
and (iii) reduce the incidence of PGD (primary graft dysfunction) in transplanted recipients. The work outlined here represents
the utilization of the cytokine adsorber in the context of lung transplantation using severely damaged donor lungs. It is thus envisioned
that adsorption may be an intervention that could lead to the acceptance of more lungs for transplantation. It may also further increase
the tolerability of such lungs in a recipient, a needed outcome given the role that PGD continues to play as the leading cause of early
mortality and as a contributor to the development of chronic graft dysfunction."
upon this work, Prof. Sandra Lindstedt and her team at Lund University Hospital, Sweden are now conducting a ten
patient randomized controlled pilot study in human lung transplantation using CytoSorb. They recently published a brief
communication based on the first 4 human lung transplant subjects, where 2 received CytoSorb intraoperatively, and 2 did not.
Those treated with CytoSorb had lower circulating nucleosome levels (inversely correlated with PGD) and did not develop PGD, while
the two patients not treated with CytoSorb had higher nucleosome levels and developed Grade 1 and Grade 3 (severe) PGD
postoperatively, respectively.
Prof. Massimo Boffini and his group from the University of Turin, Italy published the largest
retrospective human clinical study to date investigating the feasibility and safety of CytoSorb adsorption during EVLP in the
peer-reviewed journal, Transplant International. From July 2011 to March 2020, physicians performed a total of 54 EVLP procedures
on lungs that had originally failed to qualify for transplantation. Of these, 33 were performed without CytoSorb and 21 were performed
with CytoSorb integrated with EVLP. Among the 38 patients who ultimately underwent lung transplant, the CytoSorb treated group had significantly
decreased cytokines in the perfusate compared to the control group, with 76% (16/21) of lungs from the CytoSorb group qualifying for
transplantation after the EVLP procedure versus 67% (22/33) from the non-treated control. Importantly, patients receiving lung transplants
treated with CytoSorb during EVLP had significantly lower in-hospital mortality (0% vs. 13%; p=0.03) and a lower 1-year mortality rate
(0% vs. 36%; p=0.01) compared to those who received lungs treated with EVLP alone. In addition, the use of CytoSorb was associated with
a trend of fewer cases of Grade 3 severe PGD, and less need for ECMO support, which likely was associated with significant cost savings.
These results were observed despite none of these patients receiving additional intraoperative or postoperative CytoSorb treatment.
Chan, MD, PhD, Chief Executive Officer of CytoSorbents, stated, "Collectively, these data are very exciting for a number of reasons.
First, the data support the potentially pivotal role that our cytokine adsorption technologies, including CytoSorb and ECOS-300CY - which
is specifically approved in the E.U. for ex vivo organ perfusion, has in lung transplantation. We see multiple opportunities in
improving the functioning of the lung graft, expanding the donor pool of transplant-eligible lungs by reconditioning substandard ones,
and most importantly reducing the rates of severe primary graft dysfunction and mortality. Secondly, although lung transplantation is
not as common as kidney or liver transplantation, we believe the fundamental principles of cytokine reduction and treating inflammation