Medeor Therapeutics’ kidney transplant cell therapy, which combines a living donor’s cells with the recipient's, allowed more than half of study participants in a phase 3 pivotal trial to stay off immunosuppressants for two years.
The small study of 20 living-donor kidney transplant recipients found that 12, or 63%, were able to stay off immunosuppressant meds for two years, while four patients have less than six months to go in the study and remain off the drugs. Another three patients resumed immunosuppressants during the trial while one patient withdrew from the study. The protocol had anticipated a success rate of 48%.
MDR-101 is a single-dose cell therapy that is created using a living kidney donor’s blood. The goal is to help the body adjust to the new organ by inducing donor-specific immune tolerance and prevent rejection of the kidney.
Patients who receive a new kidney must stay on immunosuppressant meds for the rest of their lives to prevent rejection. But these therapies substantially increase the risk of cancer, diabetes, infection and other medical problems. Stopping or missing a dose can spur rejection of the organ, which is typically irreversible once underway. About 30% to 50% of kidney transplants fail within 10 years.
Medeor is hoping to provide another option for patients with MDR-101, which establishes a process called mixed chimerism. This occurs when a low level of donor blood cells remains in the blood of the kidney recipient after infusion of donor stem cells.
The procedure involves harvesting blood stem cells from the donor before the transplant. After the organ is transferred, the recipient is started on anti-rejection drugs and receives radiotherapy to further suppress the immune system. A few weeks later, the donor stem cells are infused into the transplant patient so they grow in the bone marrow and other immune tissues and become part of the recipient's immune system.
The phase 3 trial was testing whether kidney transplant recipients who received an organ from a matched relative with the same transplant genes could slowly taper off an immunosuppressant regimen to just tacrolimus, which is commonly used to tamp down the immune system to prevent organ rejection, within six weeks. The study further tested whether this monotherapy regimen could be cut by one year and allow patients to go without for at least two years without graft loss, death, acute kidney rejection or graft-versus-host disease.
Besides the overall rejection data, Medeor also highlighted that patients reported improved quality of life two to three years after transplant.
“By combining donor and recipient cells to create mixed chimerism and immune tolerance within the transplant recipient, we are working to alleviate the stress and burden of daily immunosuppressants, thereby improving quality of life and prolonged graft survival,” said Medeor CEO Giovanni Ferrara. “We are buoyed by the study results presented today and look forward to the completion of our study and making MDR-101 the new treatment standard for donor matched kidney transplants.”
The MDR-101 data are to be presented at the American Society of Nephrology Kidney Week 2023 Annual Meeting in Philadelphia on Friday. The therapy was granted a regenerative medicine advanced therapy designation from the FDA in 2020.
Medeor has additional programs testing cell therapies in mismatched live donor kidney transplant and delayed tolerance transplants plus a sickle cell disease program that similarly aims to induce mixed chimerism to reduce or eliminate disease symptoms.
Medeor is not the only biotech trying to come up with ways to improve life span and quality of life for organ recipients. In February, AlloVir presented early evidence for the off-the-shelf, multivirus-specific T-cell therapy posoleucel suggesting it could treat a virus that can interact with anti-rejection meds and cause issues.
But it isn't an easy road, as Talaris Therapeutics found out. The company, focused on developing new therapies for organ transplant care, eventually folded and merged with Tourmaline Bio earlier this year. The newly combined company is focused on autoimmune and inflammatory diseases.