Nearly four years after its start, a phase III trial of Gamida Cell Ltd.'s ex vivo expanded cord blood candidate, omidubicel, for hematologic malignancies is fully enrolled, the company said. The milestone puts the Jerusalem-based cell therapy developer on track to share top-line data from the study by midyear, with a potential BLA filing planned before year-end, it said. Omidubicel, formerly known as Nicord, is intended to address limitations of bone marrow transplant by providing a therapeutic dose of stem cells while preserving the cells' therapeutic character. It's also being explored as a potential therapy for severe aplastic anemia. 

CEO Julian Adams said filing the BLA would be an important step for the company in its journey toward becoming a fully integrated producer of "a potential universal bone marrow transplant solution." Shares of the company (NASDAQ:GMDA), which also has operations in Boston, rose 3.3% to close at $4.44 on Thursday. 

Omidubicel is a cryopreserved stem/progenitor cell mix comprising both umbilical cord blood-derived hematopoietic CD34+ progenitor cells and the non-cultured cell fraction of the same cord blood unit, expanded ex vivo with the company's nicotinamide-based, or NAM-based, cell expansion technology. 

In a phase I/II study of 36 patients with hematologic malignancies undergoing transplant, investigators found that the median time to neutrophil recovery for patients transplanted with omidubicel was shortened by nearly 50% vs. a retrospective cohort of patients who received standard umbilical cord blood. Among patients who engrafted, the median time to neutrophil recovery was 11.5 days (95% CI: 9-14 days) for omidubicel recipients compared to 21 days (95% CI: 20-23 days) for the retrospective cohort (p<0.001). 

Objective and measurable 

The FDA bestowed the company with the first transplant-related breakthrough therapy designation in 2016, adding to several orphan drug designations it already had. Now, in hopes that the phase III trial will yield similar results to the phase I/II, the company is in the home stretch of the global randomized study, designed to compare the safety and efficacy of omidubicel head-to-head with standard umbilical cord blood units. 

The study includes about 120 patients with high-risk hematologic malignancies who needed a bone marrow transplant but did not have an available matched donor. Its primary endpoint is time to neutrophil engraftment in participants following transplantation, which Gamida Cell's chief medical officer, Ronit Simantov, told BioWorld is "a really nice endpoint because it's objective and measurable." Secondary endpoints the company will review will evaluate the bigger picture for patients, she said, such as how long they're in the hospital, mortality related to treatment, overall survival, disease-free survival, as well as safety endpoints, such as the incidence of graft-vs.-host-disease. 

Each of the participants, ages 12 to 65, had either acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome or lymphoma. 

The shorter the time to engraftment, the better the overall outcome for patients, Adams said Dec. 5, during a talk at The 31st Annual Piper Jaffray Healthcare Conference. Patients receiving the experimental therapy are at lower risk for infections, spend fewer days in the hospital and encounter fewer complications, he said. 

Remaining need 

A total of 21,696 hematopoietic cell transplants were performed in the U.S. and reported to the Center for International Blood and Marrow Transplant Research in 2016, the most recent year for which data are available. Of those, 22% were unrelated-donor transplants. Nearly two-thirds of the unrelated transplants were performed using the peripheral blood in 2016. One-fifth used bone marrow and 14% used cord blood units. 

Despite the curative potential of bone marrow transplant, each year about 5,000 eligible patients in the U.S. don't receive transplants for various reasons, including inability to find a matched donor or lack of timely referral, the company said. Umbilical cord blood provides a good source of stem cells for patients who don't have a matched related donor, but it provides a smaller number of stem cells. "It takes a really long time for those stem cell that are there – which are terrific stem cells – to go to the bone marrow and multiply in numbers that are enough to repopulate the immunity for patients. That's always been the limitation of umbilical cord blood," Simantov said. 

Gamida Cell's NAM technology allows it to expand any type of cells, including stem cells and natural killer (NK) cells in a way that the company has said preserves the cells' original potency and function. At 2019's annual meeting of the American Society of Hematology, the company presented phase I data for its innate NK cell immunotherapy, GDA-201. In combination with monoclonal antibodies, the candidate was generally well-tolerated and demonstrated early evidence of clinical activity in heavily pretreated patients, including five complete responses and one partial response observed among nine patients with non-Hodgkin lymphoma (NHL). It also showed one complete response and five cases of stable disease for multiple myeloma patients treated with the combination. The company plans to start a phase I/II multidose study in patients with NHL in 2020. 

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