eGenesis and OrganOx have announced that the U.S. Food and Drug Administration (FDA) has cleared their investigational new drug (IND) application for EGEN-5784, a human-compatible, genetically engineered porcine liver. The system, which combines the engineered liver with OrganOx's extracorporeal liver cross-circulation (ELC) technology, is designed to treat patients with acute-on-chronic liver failure (ACLF) who are suffering from decompensated liver function in intensive care settings.
The clearance marks a significant milestone in addressing a critical unmet need for approximately 35,000 patients hospitalized annually in the United States with acute or acute-on-chronic liver failure. These patients currently face limited treatment options and mortality rates as high as 50 percent.
Novel Approach to Liver Failure Treatment
The innovative system uses eGenesis' genetically engineered porcine liver in combination with OrganOx's ELC system to support the function of a patient's failing liver. This approach may allow for the potential recovery of the patient's native liver or provide sufficient time for the patient to receive a liver transplant.
Michael Curtis, Ph.D., Chief Executive Officer of eGenesis, emphasized the significance of this development: "The FDA's clearance of EGEN-5784 in combination with the OrganOx ELC system represents a significant advance towards fulfilling our mission to develop safe and effective human-compatible organs that have the potential to transform the treatment of organ failure and extend patients' lives."
The technology has already demonstrated feasibility in preclinical studies. To date, four perfusions with decedent recipients have been completed as part of the PERFUSE-2 study, showing the potential of using EGEN-5784 with the OrganOx ELC system to support patients suffering from liver failure.
Phase 1 Clinical Trial Design
The Phase 1 trial will enroll up to 20 patients with ACLF (Grade 2 to Grade 3) and hepatic encephalopathy (≤ Grade 3) who are ineligible for transplant. The study will be conducted across multiple U.S. centers and will evaluate the safety, performance, and clinical activity of the EGEN-5784 liver in combination with the OrganOx ELC system.
Craig Marshall, Chief Executive Officer of OrganOx, highlighted the potential impact of this collaboration: "This collaboration with eGenesis demonstrates a unique application of our platform metra® technology which can potentially save the lives of patients with acute-on-chronic liver failure who have limited treatment options and face high mortality rates."
Strategic Partnership
The IND clearance follows an exclusive clinical co-development agreement between OrganOx and eGenesis established in November 2024. The partnership combines eGenesis' expertise in developing human-compatible engineered organs with OrganOx's established organ perfusion technology.
OrganOx's metra® normothermic machine perfusion (NMP) platform is already approved in the U.S., Europe, Canada, and Australia and has been utilized in over 5,000 liver transplants. The platform keeps donor livers in a metabolically active state outside the body, allowing for functional assessment prior to transplant, which has led to an increased number of organs available for transplantation.
eGenesis is pioneering a genome engineering-based approach to develop safe, effective transplantable organs to address the global organ shortage. Their platform specifically addresses cross-species molecular incompatibilities and viral risks through proprietary genetic engineering techniques.
Addressing a Critical Medical Need
Acute-on-chronic liver failure represents a significant healthcare burden with limited therapeutic options. The condition is characterized by acute deterioration of liver function in patients with pre-existing chronic liver disease, often leading to multi-organ failure and high short-term mortality.
The development of this novel perfusion system using genetically engineered porcine livers represents a potential breakthrough for critically ill patients who currently have no transplant option. If successful, this approach could significantly impact the treatment landscape for liver failure and potentially serve as a model for addressing other types of organ failure in the future.
As the clinical trial progresses, the medical community will be watching closely to see if this innovative approach can deliver on its promise to provide a lifeline for patients with one of medicine's most challenging conditions.
