United Therapeutics Shares Positive Study Results for its Bioengineered Liver

United Therapeutics Corporation is touting announced encouraging results from its phase 1 study of miroliverELAP, an external liver assist product, in patients with acute forms of liver failure, acute-on-chronic liver failure, and severe acute alcoholic hepatitis, collectively called acute liver failure (ALF).²

Approximately 30% of ALF patients die because they are ineligible for a liver transplant or a donated liver is not available.¹

Developed by Miromatrix Medical Inc., a wholly owned United Therapeutics subsidiary, miroliverELAP consists of an external blood circuit and a single-use bioengineered liver sustained outside of the human body to provide temporary liver support to ALF patients. The bioengineered liver is manufactured by seeding a decellularized porcine liver scaffold with allogeneic³ human endothelial⁴ cells and human liver cells isolated from donated human livers. The donated human livers are not suitable for transplantation and are provided by organ procurement organizations (OPOs).

“This study provides early evidence that miroliverELAP, a bioengineered organ alternative product, has the potential to provide liver support for patients experiencing ALF, giving their native livers more time to recover. Achieving this important milestone allows us to continue advancing miroliverELAP to help save and improve the lives of ALF patients, who face poor outcomes and a desperate need for therapies,” Miromatrix President Jeff Ross, Ph.D., said.

In the study, five ALF patients who were not candidates for a liver transplant were continuously treated with miroliverELAP for at least 44 hours. The single-arm, open-label, safety study met the primary endpoint of survival during miroliverELAP treatment, and there were no reports of unexpected serious adverse events attributable to the miroliverELAP over a subsequent 32-day follow-up period. Full study results will be presented and published in the second half of this year.

ALF, a devastating condition that affects thousands of patients each year, is characterized by a rapid loss of liver function in a matter of days or weeks. Approximately 45% of ALF patients will experience spontaneous recovery, while 25% will receive a liver transplant, the only effective ALF treatment. Approximately 30% of ALF patients will die because they are ineligible for a liver transplant or are unable to receive one in time due to the rapid onset of the disease and the drastic shortage of transplantable organs.⁵

United Therapeutics’ organ and organ alternative manufacturing efforts consist of three platforms—xenotransplantation,⁶ allogeneic regenerative medicine, and autologous⁷ regenerative medicine—encompassing four different organs: hearts, kidneys, livers, and lungs. These programs address the ongoing shortage of transplantable organs for patients with end-stage organ disease.

“United Therapeutics is committed to developing technologies that expand the availability of transplantable organs, and the completion of this clinical trial represents yet another historic achievement for our company. We are thrilled to see positive results from this study of miroliverELAP in ALF patients for whom liver transplantation was not an option. We sincerely thank the patients, physicians, and OPOs who made this trial possible,” United Therapeutics Chairperson/CEO Martine Rothblatt, Ph.D., stated.

Miromatrix received U.S. Food and Drug Administration clearance for its Investigational New Drug application for the phase 1 clinical trial of miroliverELAP in 2024. miroliverELAP is investigational and is not approved for any use in any country. In addition to miroliverELAP, Miromatrix is developing mirokidney, a fully transplantable bioengineered kidney, utilizing the same decellularization and seeding technology used in miroliverELAP.

United Therapeutics is the first publicly traded biotech or pharmaceutical company to take the form of a public benefit corporation (PBC). Its public benefit purpose is to provide a brighter future for patients through (a) the development of novel pharmaceutical therapies; and (b) technologies that expand the availability of transplantable organs.

References
¹ Mendizabal M, Silva MO. Liver transplantation in acute liver failure: A challenging scenario. World J Gastroenterol. 2016 Jan 28;22(4):1523-31. DOI: 10.3748/wjg.v22.i4.1523. PMID: 26819519; PMCID: PMC4721985. https://pmc.ncbi.nlm.nih.gov/articles/PMC4721985/
² More information on the study is available at https://clinicaltrials.gov/study/NCT06285253.
³ Allogeneic cells come from a donor who is genetically different from the recipient.
⁴ Endothelial cells form the inner lining of blood vessels.
⁵ Lee, W. M., Squires, R. H., Jr, Nyberg, S. L., Doo, E., & Hoofnagle, J. H. (2008). Acute liver failure: Summary of a workshop. Hepatology (Baltimore, Md.), 47(4), 1401–1415. https://doi.org/10.1002/hep.22177
⁶ Xenotransplantation is the process of transplanting living cells, tissues, or organs from one species into another—most commonly from animals into humans. United Therapeutics is conducting research involving transplantation of whole organs from gene-edited pigs into humans.
⁷ Autologous cells are cells collected from and then used in the same individual.