Gamide Cell warehouse team
Warehouse team leader Ilia Raim pulls out a cord blood unit from a liquid nitrogen storage tank at the Gamida Cell production facility in Kiryat Gat, Israel. (Photo by Larry Luxner)

KIRYAT GAT, Israel — At Gamida Cell‘s gleaming facility here—a high-tech boom town on the edge of Israel’s Negev Desert—63 workers are preparing to ramp up production of a novel infusion that outperforms umbilical cord blood in clinical trials of cancer patients undergoing stem cell transplants.

That infusion is omidubicel, an intravenous product cultured from umbilical cord blood-derived cells and modified with the company’s proprietary nicotinamide (NAM) technology, which aims to boost the amount and potency of those cells.

“There’s never been a product like omidubicel,” Gamida president and CEO Abigail Jenkins said in a recent phone interview from the company’s headquarters in Boston, Massachusetts. “Right now, we’re focusing all of our resources, human and financial, on bringing omidubicel to the US market.”

The urgency is clear: omidubicel is the first advanced cell therapy for allogeneic stem cell transplant to win breakthrough therapy designation from the US Food and Drug Administration (FDA), which could grant final approval for the treatment on May 1, 2023, under the Prescription Drug User Fee Act. Once that happens, commercial production in Israel will begin immediately.

Jenkins spoke to Rare Disease Advisor as Smitha Sivaraman, PhD, Gamida’s vice president and head of medical affairs, presented results of a real-world analysis at the 64th ASH Annual Meeting & Exposition in New Orleans, Louisiana.

Abigail Jenkins, president and CEO of Gamida Cell (Photo courtesy Gamida Cell)

The study analyzed outcomes for the 52 patients who received omidubicel against those of the 807 patients who had other donor sources from the Center for International Blood and Marrow Transplant Research database. It follows Gamida’s phase 3 randomized, double-blind, multicenter ADVANCE IV trial, which compared the safety and efficacy of omidubicel to standard cord blood.

ADVANCE IV involved 125 patients treated at more than 50 hospitals in 6 countries; 62 received omidubicel, and 63 got standard cord blood. They were 12 to 65 years old (with an average age of 38.9) and had a variety of diseases including lymphoma, leukemia, myelofibrosis, and other hematological malignancies. Just under 60% of the participants were Caucasian.

The study found that omidubicel led to a significantly faster time to neutrophil engraftment than standard cord blood. In addition, patients transplanted with omidubicel had fewer bacterial, fungal, and viral infections. And, over a 100-day period following transplant, those who got omidubicel spent an average of 0.4 days in the intensive care unit (compared to 4.7 days for those who received standard cord blood), received an average of 24.8 transfusions (compared to 35.4) and an average 6.8 consultant visits (compared to 20.1).

The results of the real-world analysis showed that omidubicel led to a median of 10 days for neutrophil engraftment, vs 15-20 days for other donor sources. In addition, overall survival was 73% for omidubicel, compared to 60% for standard cord blood. The study also met secondary endpoints: a reduction in the rate of infections, and an increase in the number of days alive and out of the hospital.

According to a company press release, “while the phase 3 study compared omidubicel to standard cord blood, these real-world data reinforce the clinical utility of omidubicel as a graft source in patients in need of an allogeneic stem cell transplant.”

Reducing the Degree of Required Matching

Gamida’s NAM technology originated in Israel—a powerhouse of innovation in the biotech industry. The company was founded in 1998, and under its previous CEO, pharmaceutical industry visionary Julian Adams, it began trials of omidubicel in 2017.

“For patients to get a bone marrow transplant, they must have a donor source,” explained Dr. Sivaraman, who was a leading biochemist in her native India before coming to the US in 1997 and joining Gamida just over 2 years ago. “Umbilical cord blood is traditionally used. However, it has some disadvantages: it takes longer to recover, and you’re more likely to get infections.”

Entrance to the 5000-square-meter Gamida Cell production facility in Kiryat Gat, Israel. (Photo by Larry Luxner)

That’s because cord blood has a relatively low dose of stem cells, compromising the chances of engraftment and delaying neutrophil and platelet recovery. Omidubicel, on the other hand, is a stem/progenitor cell-based product made up of ex vivo expanded allogeneic cells that tend to home to the bone marrow more quickly and more efficiently.

“The advantage is that because it’s derived from cord blood, you can use it for patients of ethnic or racial minorities,” she said. “It’s easy to get a match within the system if you’re Caucasian. But if you’re someone like me, or of African-American origin, it becomes increasingly difficult. With omidubicel, we’re able to get away with a lower degree of matching.”

This is particularly important, Dr. Sivaraman said, as the country becomes more racially diverse.

“The chances of someone with mixed parentage finding a match is very hard if they have a disease and need a transplant,” she said. “Given the time the patient requires, those donors might not be available. With omidubicel, we have a 30-day window in which we know we’ll get the product delivered, so it’s very predictable.”

Gamida Also Sees Potential in Other Regions

At present, about 40% of US patients who qualify for a stem cell transplant don’t get one for various reasons, including the lack of a matched donor, according to Gamida.

Yeshayahu Kaufman and Gennadiy Stepanenko work in one of several clean rooms at the Gamida Cell production facility in Kiryat Gat, Israel. (Photo by Larry Luxner)

Healthcare costs are another factor. In a June 2020 paper, Frances Verter, PhD, cited a RAND Corp. survey showing that in 2014, the average hospital charges for a stem cell transplant from an unrelated donor (and duration of hospital stay) came to $485,000 (38 days) for bone marrow, $571,000 (34 days) for peripheral blood stem cells, and $831,000 (51 days) for cord blood.

“The biggest factor contributing to the higher cost of cord blood transplants was the longer time to engraftment, which translates into more days in intensive care and more complications from infections,” Dr. Verter wrote. “Gamida Cell has removed that disadvantage by driving down the engraftment time of a cord blood transplant so that it is competitive with bone marrow and peripheral blood transplants.”

Omidubicel is shipped in these specialized containers from Israel to Gamida’s clients in the United States. (Photo by Larry Luxner)

Omidubicel is already being shipped in specialized containers directly from Gamida’s 5000-square-meter Kiryat Gat factory to hospitals and transplant centers in the United States, where doctors administer the medication to patients through an infusion.  

Drawn by local tax incentives, the company in June 2021 established its facility in Kiryat Gat, about a 45-minute train ride south of Tel Aviv. The plant happens to be located across the street from semiconductor maker Intel, which recently announced an $11 billion expansion of its chip factory there.

Gamida currently employs 146 people, both in Israel and at its Boston corporate headquarters. Eventually, the company would like to ship its lead product to other countries too.

“We believe that there’s market potential for omidubicel in markets like Europe, Japan, Canada, and other markets around the world where there are similar patients in need of an advanced, alternate donor source,” Jenkins said. “We’re interested in exploring partnerships with companies that may have already established infrastructure to take it to these other jurisdictions.”