FDA Accepts BLA And Grants Priority Review to Omidubicel in Hematologic Malignancies

Based on results from a phase 3 trial, the FDA has accepted a biologics license application for and granted priority review to omidubicel for those with hematologic malignancies who require allogenic hematopoietic stem cell transplant.

The FDA has accepted a biologics license application for and granted priority review to omidubicel as a potential treatment for patients with blood cancers who need an allogeneic hematopoietic stem cell transplant, according to a press release from Gamida Cell.1

The application is supported by results from a phase 3 trial (NCT02730299) that assessed the safety and efficacy of omidubicel vs standard umbilical cord blood transplant in patients with hematologic malignancies such as lymphoma, leukemia, and myelodysplastic syndrome. The FDA has set a prescription drug user fee act date of January 30, 2023.

“The FDA’s acceptance of our biologics license application with priority review signifies a critical milestone in our mission to deliver a new stem cell therapy option for patients in need of a donor for an allogeneic stem cell transplant,” Julian Adams, PhD, chief executive officer at Gamida Cell, said in the press release. “We are encouraged by the positive and sustained follow-up results from patients participating in the phase 3 trial of omidubicel, including a positive overall survival trend 1-year out from treatment. These results provide a promising rationale that, if approved, omidubicel could become a treatment of choice for patients in need of an allogeneic hematopoietic stem cell transplant. We look forward to working with the FDA throughout the review process to bring omidubicel to patients as quickly as possible.”

Results from the study were previously published in Blood in 2021.2 A total of 125 patients were enrolled and randomly assigned to either the omidubicel arm (n = 62) or the umbilical cord blood graft arm (n = 63). Omidubicel was not given to 10 patients per protocol, and 8 patients in the control arm also did not receive treatment. Those receiving omidubicel underwent transplantation at a median of 41 days compared with 26 days for standard umbilical cord blood transplantation.

The time to neutrophil count recovery was 12 days (95% CI, 10-14) in the omidubicel arm and 22 days (95% CI, 19-25) in the control arm (P <.001). On day 42 after receiving transplantation in the omidubicel arm within the as-treated population (n = 52), the cumulative incidence of neutrophil engraftment was 96% with a median of 10 days (95% CI, 8-13) vs 89% with a median of 20 days (95% CI, 18-24) in control arm (n = 56; P <.001). Patients in the omidubicel cohort had more CD34-positive cells (r = –.66; P <.001) and CD34-positive cell doses per weight vs the control arm, which was associated with shorter times to neutrophil engraftment (r = –.62; P <.001).

After patients received transplantation on day 42, the cumulative incidence of platelet engraftment in the omidubicel arm was 55% vs 35% in the control arm (P = .028). By day 100, the cumulative incidence of platelet engraftment was 83% at a median of 37 days (95% CI, 33-42) compared with 73% and a median of 50 days (95% CI, 42-58; P = .023) in the control arm.

On day 30 and beyond and day 100 and beyond after transplantation, full donor chimerism occurred in all but 2 patients receiving omidubicel with 1 patient having an early relapse and the other having primary graft failure. On day 42 and onward, 6 patients who received umbilical cord blood transplants experienced graft failure.

At day 100, the incidence of acute graft-versus-host disease (GVHD) of grades 2 to 4 was 56% in the omidubicel arm vs 43% in the control arm (95% CI, –6% to 30%; P = 18). On day 100, grade 3 to 4 aGVHD was similar between arms at 14% vs 21% (95% CI, –21% to 7%; P = .33), respectively. In the omidubicel arm, the 1-year cumulative incidence of chronic GVHD was 35% compared with 29% in the control arm (95% CI, –14% to 25%; P = .57). Moderate-to-severe chronic GVHD at 1-year was 27% in the omidubicel arm vs 21% in the control arm (95% CI, –11% to 24%; P = .49).

The median follow-up was 10 months following transplantation. Non-relapse mortality rate at 210 days was 11% in the omidubicel arm and 24% in the control arm (P = .09). At 15 months, disease relapse rate was 25% in the omidubicel arm and 17% in the control arm (P = .32). Relapse occurred in 4 patients in each arm.

The HR for treatment failure included relapse or death and inverse relapse-free survival (RFS) was 0.79 (95% CI, 0.45-1.38; P = .4). Adjusted HR for mortality between both arms was 0.57 (95% CI, 0.3-1.1; P = .09). At 1-year, the GVHD-free RFS was 36% in the omidubicel arm vs 45% in the control arm (P = .56). Eleven patients died in the omidubicel arm vs 18 in the control arm. Of these patients, 2 in the omidubicel arm died from relapsed disease vs 4 in the umbilical cord blood arm.

References

  1. Gamida Cell announces FDA acceptance of biologics license application for omidubicel with priority review. News release. August 1, 2022. Accessed August 2, 2022. https://bit.ly/3BIQj2i
  2. Horwitz ME, Stiff PJ, Cutler C, et al. Omidubicel vs standard myeloablative umbilical cord blood transplantation: results of a phase 3 randomized study. Blood. 2021;138(16):1429-1440. doi:10.1182/blood.2021011719