Omidubicel, a novel cellular therapy, expands the availability of allogeneic (donor) stem cell transplants to more patients

On April 17, 2023, the U.S. Food and Drug Administration (FDA) approved omidubicel — a new and potentially life-saving stem cell treatment option for adult and pediatric patients with high-risk blood cancers, including leukemia and lymphoma.

Omidubicel, which is being marketed by Israel-based Gamida Cell Ltd. under the brand name Omisirge^®, is a donor umbilical cord blood–based cellular therapy — the first and only modified allogeneic (donor) umbilical cord blood–based stem cell transplant product to receive Breakthrough Therapy designation from the FDA.

Omidubicel’s approval was backed by promising results from a multi-center international phase 3 clinical trial led by Mitchell Horwitz, MD, director of the Adult Blood and Marrow Transplant Program at Duke Cancer Institute (DCI). Investigators found that the omidubicel product worked better and faster and was safer than a conventional umbilical cord blood stem cell transplant. The findings were published in October 2021 issue of the journal Blood, with Horwitz as lead author. A health-related, quality-of-life, 10-year follow-up study, led by DCI Hematology-Oncology Fellow Chenyu Lin, MD, was published in January 2023 in the journal Transplantation and Cellular Therapy.

Omidubicel expands access to needed treatment for adults and children over 12 who are unable to receive a bone-marrow-derived allogeneic stem cell transplant (the most common type of stem cell transplant) because they can’t find a genetically similar related or unrelated donor “match,” and who are too big to receive a conventional umbilical cord blood–based stem cell transplant, which doesn’t require a match.

“Stem cells are dosed based on body weight. The larger you are, the less likely you are to find a large enough unit of cord blood, which is why cord blood–based stem cell transplants have historically had more success in small children,” explained Horwitz. “A low dose of cord blood stem cells can work but may lengthen and/or compromise the chances of engraftment — when donor stem cells settle into the patient’s bone marrow or 'home in' and begin growing new red and white blood cells and platelets.”

Omidubicel takes care of the volume issue — the biggest drawback to a cord blood–based stem cell transplant — by expanding it. The cellular therapy (omidubicel) is manufactured by culturing (in a dish in the lab) and multiplying donor cord blood stem cells and progenitor cells for three weeks in the presence of nicotinamide, a derivative of vitamin B3 (niacin). Nicotinamide, said Horwitz, is believed to be the key component of the culture system that allows for safe and effective growth of the cord blood progenitor cells, whose capacity for self-renewal is more limited than that of stem cells. (Progenitor cells are descendants of stem cells. The two are similar in that they can self-renew and differentiate into/grow specific types of cells. Self-renewal in progenitor cells is limited, however, and unlike stem cells, which can differentiate into any cell type in the blood, progenitor cells may only be able to differentiate into one or two cell types.)

How It Works

Once the patient has undergone “conditioning” — high-intensity chemotherapy and/or radiation to destroy their cancer cells — the high-volume omidubicel mix is then transferred to the bloodstream of the patient. The conditioning treatment also weakens the patient’s immune system, thereby reducing the chance that the omidubicel mix will be rejected on its journey to the patient’s bone marrow. If all goes to plan, the donor stem cells will self-renew and replace the patient’s stem cells that were destroyed by the conditioning treatment, as well as replenish the patient's supply of red blood cells, white blood cells, and platelets.

“Scientists believed that the larger number of stem and progenitor cells in omidubicel would allow the body to recover its neutrophils (the most common type of white blood cell) and other blood cells faster than a much-lower-volume conventional cord blood stem cell transplant,” said Lin. “The clinical trial confirmed their hypothesis.”

“The clinical trial I led exceeded expectation,” said Horwitz. “Not only did it meet the primary endpoint of faster neutrophil engraftment (12 days vs. 22 days), but it showed significant efficacy among a number of secondary endpoints as well, including reducing bacterial, fungal, and viral infections, and improving patients’ quality of life. Patients are profoundly vulnerable to infection prior to neutrophil recovery, so even reducing the process by a few days made a difference.”

Investigators found that patients spent “significantly fewer” days in the hospital during the first 100 days after transplantation (a median of 48 days vs 61 days) — including intensive care unit time, consultant visits, procedures, and transfusions — than those who received a conventional umbilical cord blood stem cell transplant.

According to the National Marrow Donor Program, 70% of patients in need of a stem cell transplant do not have a fully matched family donor (a sibling is the preferred source) and must use stem cells either from an unrelated matched (genetically similar) donor or from donated cord blood. The chance of finding a fully matched unrelated donor ranges from 30% to 80% depending on ethnic background.

“If they can’t find a fully matched unrelated donor, they would need to look for an alternative stem cell source that is not fully matched: their parents or children, a mismatched unrelated donor, or cord blood,” explained Lin.

Lin, who was involved in the analysis of secondary endpoints of the trial and led the long-term follow-up study, elaborated in an interview with Targeted Oncology last fall on how the new treatment will help to mitigate healthcare disparities.

“We’ve really been able to increase the diversity of our stem cell registries in the past decade, but there are still some healthcare disparities present in terms of being able to find an optimal match with an unrelated donor,” said Lin. “For an individual of Northern European descent, that’s relatively easier, but for certain under-represented ethnic and racial minority groups, the rates of being able to find an optimal match is much lower. So, this is where an alternative stem cell source like cord blood can come in. The hope, with the long-term safety data being reassuring for omidubicel, is that we’re going to be able to expand access to stem cell transplantation for patients who otherwise would not have an adequate donor, but who are nonetheless reliant on transplant as the only curative therapy for their disease. I think it’s an exciting time for cord (blood) expansion, and omidubicel is leading the way for potentially paradigm-shifting developments in the field."

The Blood Cancer Center at DCI has already treated five patients with an omidubicel on a “compassionate use” basis. FDA approval means that many more patients can now gain access to this novel cell therapy product.

Institutional support for the phase 3 clinical trial “Stem Cell Transplantation With NiCord® (Omidubicel) vs Standard UCB in Patients With Leukemia, Lymphoma, and MDS” (NCT 02730299) was provided with research funding by Gamida Cell Ltd.