Pre-BLA Meeting Held With FDA for Omidubicel in Select High-Risk Hematologic Malignancies

Gamida Cell Ltd. has completed a Type B Pre-Biologics License Application (BLA) meeting with the FDA to discuss the investigational advanced cell therapy omidubicel as a potential therapeutic option for patients with blood cancers who require stem cell transplant.¹

In the meeting, the regulatory agency requested that the company provide a revised analysis of the manufacturing information that was produced by the company’s commercial manufacturing facility to showcase how it compares with how the agent was produced at manufacturing sites utilized for the phase 3 trial (NCT02730299). Additional clinical data to initiate the submission of the application was not requested.

“Despite the delay in timing to bring omidubicel to patients after a potential FDA approval, we are encouraged by the FDA’s reaction to our phase 3 data as the pivotal trial of [the agent],” Julian Adams, PhD, chief executive officer of Gamida Cell, stated in a press release. “We have gained further clarity with the FDA on the requirements for demonstrating comparability for our commercial manufacturing facility. With the FDA’s feedback in hand, we believe that we are one step closer for omidubicel to be made available to patients in need.”

Omidubicel is comprised of 2 cryopreserved fractions derived from a single entire cord blood unit and is thawed at transplant centers immediately before infusion.² The cells are collected after CD133+ selection ex vivo expanded for 21 days in the presence of nicotinamide. The agent is also composed of non-cultured CD133-negative cells that include T cells.

Data presented during the Virtual 47th Annual Meeting of the EBMT from the phase 3 trial showed that omidubicel was linked with a significantly improved median time to neutrophil engraftment vs standard umbilical cord blood (UCB) transplantation in patients with high-risk hematologic malignancies.

In the intent-to-treat (ITT) population (n = 125), the median time to neutrophil engraftment was 12.0 days (95% CI, 10.0-15.0) with omidubicel vs 22.0 days (95% CI, 19.0-25.0) with UCB (P < .001). In the as-treated population (n = 108), the median times in the investigative and control arms were 10.0 days (95% CI, 8.0-13.0) and 20.5 days (95% CI, 18.0-24.0), respectively (P < .001).

The agent also resulted in a 41% reduction in the risk of death vs standard UCB (HR, 0.59; 95% CI, 0.29-1.12; P = .16), although the study was not powered to look at overall survival.

The phase 3 study enrolled patients with high-risk acute myeloid leukemia (n = 60), acute lymphoblastic leukemia (n = 41), myelodysplastic syndromes (n = 9), chronic myeloid leukemia (n = 6), lymphoma (n = 5), and rare leukemia (n = 4). To be eligible for enrollment, patients needed to be between the ages of 12 years and 65 years, be eligible for allogeneic stem cell transplant, and not have a matched donor.

Study participants were randomized 1:1 to receive the cell therapy or standard UCB. Cord blood units were selected before randomization, and this was stratified by treatment center, disease risk index, age, and intent to perform single vs double cord transplant in the control arm.

The primary end point of the trial was time to neutrophil engraftment, and key secondary end points included time to platelet engraftment, infections by 100 days following transplant, and hospitalizations, which was defined as the days alive and out of the hospital in the first 100 days following transplant.

Of the 125 patients who comprised the ITT population, 62 received omidubicel and 63 underwent standard transplant. Of the 108 patients in the as-treated population, 52 received the cell therapy and 56 received the control, per study protocol.

Patient characteristics were noted to be balanced between the 2 treatment arms. The median age of participants was 41.5 years, and 57.5% were male. The majority of patients were White (58%), and 13% of patients were Latino. Moreover, 24% of patients had low-risk disease, 42% had moderate-risk disease, and 34.5% had high- or very high-risk disease.

The myeloablative conditioning regimens were 2 total body irradiation-based regimens comprised of thiotepa, fludarabine, and cyclophosphamide (48.5%) or 1 with thiotepa, busulfan, and fludarabine (44.0%).

In the first cord blood unit, the HLA match was 4/6 in 73.5% of patients, 5/6 in 24.5%, and 6/6 in 2%. In those who had been given a second cord blood unit, which only applied to the control arm, the HLA matches occurred in 74.0%, 24.0%, and 2.0% of patients, respectively. Moreover, 32.5% of patients had a single intended UCB transplant, and 67.5% had a double.

Additional findings indicated that the median CD34-positive cell expansion was 130-fold (range, 32-233). In the ITT population, the cumulative day 42 incidence of platelet engraftment was 55% and 35% in the investigative and control arms, respectively (95% CI, 0.03-0.35; P = .028). In the as-treated population, the median time to platelet engraftment was 37 days (95% CI, 33.0-42.0) with omidubicel and 50 days (95% CI, 42.0-58.0) with the control (P = .023).

A trend toward lower non-relapse mortality was observed with omidubicel vs the control (P = .09), but the risk for relapse was comparable between the arms (P = .32). Moreover, the disease-free survival rate was higher in the investigative arm vs the control (P = .68).

Regarding safety, those in the ITT population who received the cell therapy experienced a lower rate of grade 2 or 3 bacterial or invasive fungal infection by 100 days, at 37.0% and 57.0%, respectively (P = .027). The rates of viral infections in the investigative and control arms were 10.0% and 26.0%, respectively (P = .029).

Those who received the cell therapy had a median of 60.5 days alive and out of hospital in the first 100 days following transplant vs a median of 48.0 days with the control (P = .005).

No significant difference in incidence of graft-versus-host disease (GVHD) was observed between the arms (P = .18), nor grade 3/4 GVHD (P = .33); this trend held up with chronic GVHD at 1 year (P = .57).

Gamida Cell Ltd. stated that it will continue to work with the FDA to address its request, and shared plans to submit the BLA in the first half of 2022.

References

1. Gamida Cell provides update on pre-BLA meeting with FDA for omidubicel. News release. Gamida Cell Ltd. November 11, 2021. Accessed November 11, 2021. https://bit.ly/3ohmFJm
2. Sanz GF, Stiff PJ, Cutler CS, et al. Results of a phase III randomized, multicenter study comparing omidubicel with standard umbilical cord blood transplantation (UCBT) in patients with high-risk hematologic malignancies following myeloablation. Presented at: 47th Annual Meeting of the EBMT; March 14-17, 2021; Virtual. Abstract GS2-7.