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Gamida Cell's StemEx Improves Overall Survival in Phase II/III


By Marie Powers
Staff Writer

Israeli biotech Gamida Cell Ltd. moved lead product StemEx one step closer to becoming potentially the first allogeneic biologic cell product to achieve marketing approval in the U.S. and Europe. The therapy, which uses the company's copper chelator technology, demonstrated overall survival – the primary endpoint – in a Phase II/III study comparing its use in a transplantation regimen to historical controls when treating patients with hematologic malignancies such as leukemia and lymphoma who could not find a family-related matched bone marrow donor following myeloablative therapy.

The study included 101 patients recruited from 25 bone marrow transplant centers around the world. The primary endpoint was defined as the rate of mortality within 100 days following transplantation. For the final analysis, the historical control cohort was composed of a similar group of patients each transplanted with double cord blood between 2006 and 2010. The analysis showed 15.8 percent mortality in the StemEx group compared to 24.5 percent in the control group (p = 0.034).

Jerusalem-based Gamida Cell did not disclose additional details, but Yael Margolin, the company's president and CEO, said a complete analysis of the trial data will be reported in a few weeks. Once those analyses are in hand, the company plans to meet with the FDA and the European Medicines Agency to discuss the regulatory path for the product, which will be submitted concurrently in the U.S. and European Union. A new drug application is likely next year, following CMC and other studies, she added.

StemEx is a graft of stem/progenitor cells isolated and expanded from a portion of a single unit of umbilical cord blood and transplanted in combination with nonexpanded cells from the same unit. The StemEx program has orphan drug status from the FDA for use as hematopoietic support in relapsed or refractory blood cancer patients receiving high-dose therapy.

Although such patients become candidates for bone marrow transplants, fewer than 40 percent find matches enabling them to have the procedure. For the majority, the primary clinical approaches include the use of double units or mixed matches of cord blood, neither of which offers an optimum solution. "There is a tremendous need for a product that will improve clinical outcomes," Margolin said.

Other companies are testing the use of stem cell therapies in related indications. For example, in 2011, the FDA cleared Melbourne, Australia-based Mesoblast Ltd. to begin a Phase III trial of its off-the-shelf mesenchymal precursor cells (MPC) in an effort to reproduce positive results from a pilot trial at the University of Texas MD Anderson Cancer Center. In that study, the product was found to accelerate neutrophil and platelet recovery, with high 100-day patient survival and low rates of graft-vs.-host disease (GVHD). (See BioWorld Today, July 8, 2011.)

In 2010, Mesoblast inked a $350 million strategic alliance with Cephalon Inc. (now part of Teva Pharmaceutical Industries Ltd.) to develop and commercialize its MPC therapeutics for hematopoietic stem cell transplantation in cancer patients and other indications. (See BioWorld Today, Dec. 9, 2010.)

Last year Health Canada approved Prochymal (remestemcel-L), Osiris Therapeutics Inc.'s allogeneic stem cell treatment, in GVHD, but the treatment has not yet received approval in the U.S. or Europe. (See BioWorld Today, May 23, 2012.)

The StemEx technology, developed by company co-founder Tony Peled, who now serves as chief scientific officer and vice president of research and development, is the first to complete a Phase III study in the transplantation regimen, according to Margolin.

The technology is a key differentiator, since StemEx is based on the expansion of one unit of umbilical cord blood rather than conventional approaches, which use two. Cord blood has fewer matching requirements than bone marrow or peripheral blood transplants, providing the potential to increase the number of suitable transplant matches and to shorten the time it can take to find a match. However, cord blood contains a limited number of stem or progenitor cells, typically restricting use of a single unit to pediatric treatment. A single unit of cord blood costs about $40,000 in the U.S., Margolin pointed out.

The StemEx program was developed by the Gamida Cell-Teva Joint Venture, equally owned by Gamida Cell and Teva, also of Jerusalem. Although the joint venture owns the product's global commercialization rights, Gamida Cell is driving the decision about whether to partner the product commercially or go it alone – a possibility the company is "seriously evaluating," Margolin said.

Aimed at a niche market of approximately 150 bone marrow transplant centers worldwide, the product could be managed with a relatively small sales force.

"Partnering has significant advantages, but you have to find the right partner," Margolin told BioWorld Today, noting that the company will entertain those discussions after meeting with the FDA. If Gamida Cell should decide to take StemEx to market independently, "we would definitely need to raise a large sum of money," she noted. She said all options would be on the table, including an initial public offering, although "it's too early in the process" to make that decision.

In addition to Teva, the company's existing investors include Elbit Imaging, Clal Biotechnology Industries, Israel Healthcare Venture, Amgen, Denali Ventures and Auriga Ventures.

Behind StemEx, Gamida has a second platform based on nicotinamide (NAM), a form of vitamin B3 and an inhibitor of enzymes that use NAD as a co-factor for their activity. Therapies using the NAM technology, including NiCord in hematologic cancers and hemoglobinopathies and CordBridge in neutropenia and acute radiation syndrome, have advanced into multiple clinical studies.