Patient discharged with eGenesis’ genetically engineered pig kidney after successful xenotransplant procedure

2024-04-04

临床研究

来源: FierceBiotech

“This moment—leaving the hospital today with one of the cleanest bills of health I’ve had in a long time—is one I wished would come for many years," said the patient, Richard Slayman, in a statement through Massachusetts General Hospital.

A man with end-stage renal disease is now healthy enough to be discharged from the hospital, after becoming the first in the world to receive a kidney transplant from a genetically engineered pig.

Developed by eGenesis, the xenotransplant organ underwent CRISPR editing to knock out three pig genes tied to proteins that can trigger severe rejections by the human immune system—with the goal of dramatically increasing the availability of donor tissue.

The former Fierce Medtech Fierce 15 winner also took the opportunity to insert seven human-derived sequences of genetic code, to help tamp down the body’s inflammation and coagulation responses. Finally, eGenesis’ process cleaned up multiple retroviruses that had inserted themselves into the porcine DNA, resulting in 69 genomic edits in total.

“This successful procedure heralds a new era in medicine in which we have the potential to eliminate organ supply as a barrier to transplantation and realize our vision that no patient dies waiting for an organ,” eGenesis CEO Michael Curtis said in a statement.

The patient, 62-year-old Richard Slayman, previously received a kidney transplant from a human donor, after being on dialysis for seven years. However, that organ began showing signs of failure about five years later, and he was unable to continue dialysis treatments after repeated complications in accessing his bloodstream.

But after a four-hour procedure in mid-March conducted by transplant surgeons at Massachusetts General Hospital, his new kidney is functioning well.

“This moment—leaving the hospital today with one of the cleanest bills of health I’ve had in a long time—is one I wished would come for many years. Now, it’s a reality and one of the happiest moments of my life,” Slayman said in a statement from MGH, adding that his recovery is “progressing smoothly.”

Slayman also received a pair of novel drugs to suppress his immune system, including Eledon Pharmaceuticals’ tegoprubart and Alexion Pharmaceuticals’ ravulizumab. The entire procedure was performed under the FDA’s expanded access protocol, which grants a go-ahead under compassionate use in specific cases and will require long-term monitoring.

eGenesis estimates that more than 800,000 people in the U.S. and millions more worldwide suffer from renal failure—while more than 90,000 names currently sit on the wait list for a kidney, and only 25,000 transplants are performed each year.

“Nearly seven decades after the first successful kidney transplant, our clinicians have once again demonstrated our commitment to provide innovative treatments and help ease the burden of disease for our patients and others around the world,” said Mass General Brigham President and CEO Anne Klibanski, M.D., referring to the world-first human organ transplant performed at Brigham and Women’s Hospital in 1954.

eGenesis has also been developing potential liver transplants derived from pigs through the same gene-editing process. In January, the company—alongside the organ perfusion hardware maker OrganOx—announced it was able to successfully circulate human blood through an external liver connected to the body of a brain-dead research donor.

Performed at the University of Pennsylvania, eGenesis said that no evidence of rejection was observed during the 72 hours of perfusion time while stable blood flow and pressure supported “robust bile production.”

eGenesis and OrganOx plan to develop the technology into an extracorporeal therapy that may provide enough time for a patient’s native liver to recover, or as a bridge to an eventual transplant. The companies said they plan to submit an application to the FDA this year for permission to launch a first-in-human clinical study.

Meanwhile, companies such as United Therapeutics’ organ manufacturing subsidiary Revivicor have seen progress with genetically engineered tissues, including a pig kidney that also includes a portion of the same animal’s thymus gland to help it pass inspection by the human immune system.