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Update on Omidubicel from Gamida Cell: Phase 3 Trial Outcomes

March 2021
Frances Verter, PhD

 

Omidubicel is a proprietary stem cell product (formerly known as NiCord®) produced by Gamida Cell that is manufactured from expanded cord blood. Omidubicel has been through multiple clinical trials to prove its value as an alternative graft source for stem cell transplants. In the phase 3 clinical trial NCT02730299, a unit of cord blood converted to Omidubicel was given standalone against a control arm consisting of single or double cord blood transplants. Gamida Cell reported in May 2020 that Omidubicel met the primary trial endpoint of speeding up neutrophil engraftment. The Omidubicel engraftment was even faster than bone marrow transplants, and we discussed the implications in our newsletter of June 2020. Since then, Gamida Cell reported in Oct. 2020 that Omidubicel met all the secondary endpoints of the phase 3 trial, which are summarized in the second table below.

Gamida Cell plans to submit an FDA Biologic License Application (BLA) for Omidubicel in the second half of 2021 (this was previously planned as a rolling submission). Gamida Cell Ltd. (Nasdaq: GMDA) joined the Nasdaq biotech index on 21 Dec. 2020 after a $75 million IPO. Currently, in March 2021, the share price of Gamida Cell is about double the value it held through most of 2020.

Demographics of
Omidubicel Phase 3 Trial

Omidubicel
Transplant

Standard
Cord Blood Transplant

# Patients in group

52

56

Patient age

40 (13-62)

43 (13-65)

Patient weight

78.6 kg (43-134)

77.4 kg (46-133)

Race White/Black/Asian/Other

57% /18% /11% /15%

59% /14% /16% /11%

Diagnosis AML/ALL/MDS/Other

44% /32% /10% / 15%

52% /33% /5% /9%

Conditioning includes TBI

50%

47%

HLA match 4/6, 5/6, 6/6

74% /24% /2%

73% /25% /2%

Cell therapy TNC dose

47 M/kg (17-124)

50 M/kg (25-96)

 

Statistically Significant Median Outcomes of
Omidubicel Phase 3 Trial

Omidubicel
Transplant

Standard
Cord Blood Transplant

Cell therapy CD34+ dose

9.0 M/kg (2.1-47.6)

0.3 M/kg (0.1-1.0)

Time to neutrophil engraftment (ANC>500)

10.0 days (95% CI, 8-13)

20.5 days (95% CI, 18-24)

Time to platelet engraftment (PLT>20 B/L)

37 days (95% CI, 33-42)

50 days (95% CI, 42-58)

Cumulative Platelet engraftment by day 42

55%

35%

Incidence grade 2/3 infection, bacterial or fungal, by day 100

37%

57%

Incidence grade 3 infection, viral, by day 100

10%

26%

# Days out of hospital during first 100

60.5

48.0

 

As the table above summarizes, the Omidubicel phase 3 trial achieved statistically significant outcomes for their three secondary endpoints1: platelet engraftment, infections, and hospitalization. The significant decreases seen in infections and duration of hospitalization were primarily a consequence of the more rapid neutrophil engraftment. 

It is also notable where the outcomes of the two trial arms did not differ significantly1: While Omidubicel engrafted dramatically faster, the cumulative neutrophil engraftment at day 42 was similar on the two arms: 96% for Omidubicel patients and 89% for standard cord blood transplants. At one year past transplant, the overall incidence of chronic graft versus host disease (GvHD) was not significantly different between the Omidubicel arm and the standard cord blood transplants. The arms also did not have significant differences in terms of  grade 2 or higher acute GvHD, incidence of relapse within 15 months, non-relapse mortality, disease-free survival, or overall survival. It is important to note that the trial was not powered to detect differences in long-term outcomes, so these results are not surprising. Gamida Cell has been running clinical trials of Omidubicel (formerly known as NiCord®) for over a decade, and the long-term engraftment is stable1.

expanded cord blood transplant is like a gryphonIn summary, Omidubicel transplants mimic the short-term advantages of bone marrow but have the long-term advantages of cord blood. This expanded cord blood product is like a gryphon, a mythical creature with the head and shoulders of an eagle but the hindquarters of a lion. In the short term, Omidubicel engrafts a few days faster than the median for either standard bone marrow transplants or haploidentical bone marrow transplants2,3. But the long-term performance of Omidubicel has the benefits of a cord blood transplant: lower GvHD4 and presumably anti-leukemia activity5.

An Expanded Access Program NCT04260698 now offers Omidubicel to patients with various hematologic malignancies; six clinical sites in the United States are currently recruiting. The open-ended nature of this program will attract oncologists and patients who did not want to participate in a trial where they might be randomized to the treatment arm giving a standard cord blood transplant.

As transplants with Omidubicel become more common, Gamida Cell will have to keep up with demand to manufacture the product. Gamida Cell has two manufacturing centers, one located in Israel and the other in the Netherlands. The manufacturing process takes three weeks and starts with a large cord blood unit (CBU), one that has an initial Total Nucleated Cell (TNC) count over 1.8 billion cells. This demand for large CBU is consistent with current guidelines for all cord blood transplants, which call for CBU that can provide at least 25M cells/kg for patients with malignancies6. Less than 20% of the inventory in public cord blood banks meets this size threshold, but those units comprise the majority of CBU released for transplants7,8.

The Gamida Cell product Omidubicel continues to lead the pack of expanded cord blood products that seek to make cord blood transplants more feasible for a wider group of patients. The clinical success of Omidubicel is pushing the envelope of current practices in stem cell transplants. Hopefully it will be approved by the FDA and that will lead to an educational campaign to offer this option to physicians and patients. It has already spurred greater capital investment in expansion technologies. Ultimately, increased utilization of public cord blood inventories for expanded products may lead public health agencies to revisit the need for ongoing collections of cord blood donations.

References

  1. Horwitz ME, Stiff P, Rezvani AR, et al. Improved clinical outcomes with omidubicel versus standard myeloablative umbilical cord blood transplantation: results of a phase III randomized, multicenter study. Presented at: 2021 Transplantation and Cellular Therapy Meetings; February 8-12, 2021; Virtual Abstract 34.
  2. Eapen M, Rubinstein P, Zhang M-J, et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet 2007; 369(9577):1947-1954.
  3. Bashey A, Zhang M-J, McCurdy SR, ... Eapen M. Mobilized Peripheral Blood Stem Cells Versus Unstimulated Bone Marrow As a Graft Source for T-Cell–Replete Haploidentical Donor Transplantation Using Post-Transplant Cyclophosphamide. J Clinical Oncology 2017; 35(26):3002–3009.
  4. Eapen M, Rocha V, Sanz G, ... Wagner JE. Effect of graft source on unrelated donor haemopoietic stem-cell transplantation in adults with acute leukaemia: a retrospective analysis. Lancet 2010; 11(7):653-660.
  5. Milano F, Gooley T, Wood B, ... Delaney C. Cord-Blood Transplantation in Patients with Minimal Residual Disease. NEJM 2016; 375:944-953.
  6. Politikos I, Davis W, Nhaissi M, ... Barker JN. Guidelines for Cord Blood Unit Selection. BBMT 2020; 26(12):2190-2196.
  7. Parent's Guide Cord Blood Foundation. RAND Corporation report on Public Cord Blood Banking Industry. Newsletter Published Nov. 2017
  8. World Marrow Donor Association. WMDA Global Trends 2019. Annual Report Published 2020-07-14