FDA Grants Orphan Drug Designation to HQP1351 in Chronic Myeloid Leukemia
May 04, 2020 08:00pm
"These results have the potential to substantially move the field forward and represent an important step toward making stem cell transplantation more accessible and more successful for patients with lethal blood cancers. Shortening the time to engraftment is clinically meaningful, as it can reduce a patient’s time in the hospital and decrease likelihood of infection."
Omidubicel (Cordin) led to a significant decrease in the time to neutrophil engraftment compared with standard umbilical cord blood in patients with high-risk hematologic malignancies in need of a bone marrow transplant, according to topline results from a phase III trial announced by Gamida Cell in a press release.1
The median time to neutrophil engraftment with omidubicel was 12 days (95% CI, 10-15 days) compared with 22 days (95% CI, 19-25 days) in the comparator arm (P <.001), which met the primary end point for the trial. The product was also considered to be well tolerated.
A Biologics License application for omidubicel is expected to be submitted on a rolling basis starting in the fourth quarter of 2020.
"I’m very encouraged by the data from this rigorous, phase III study that was conducted at more than 50 centers around the world, as there is a significant need for new bone marrow transplant graft modalities,” said principal investigator Mitchell Horwitz, MD, who is a professor of medicine at the Duke Cancer Institute, in the press release. “These results have the potential to substantially move the field forward and represent an important step toward making stem cell transplantation more accessible and more successful for patients with lethal blood cancers. Shortening the time to engraftment is clinically meaningful, as it can reduce a patient’s time in the hospital and decrease likelihood of infection.”
Omidubicel is an advanced cellular therapy being developed as a bone marrow transplant product. It consists of ex vivo expanded allogeneic cells from one unit of umbilical cord blood. Using the small molecule nicotinamide, the product inhibits differentiation and increases homing to the bone marrow and the efficiency of engraftment of hematopoietic CD34-positive progenitor cells.
The international, multicenter, randomized phase III trial (NCT02730299) is exploring the safety and efficacy of omidubicel transplantation in comparison with unmanipulated cord blood transplantation in patients with hematologic malignancies. A total of 125 patients between the ages of 12 and 65 years were enrolled in the study. Patients had acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome or lymphoma. Those with another active malignancy, infection, or central nervous system disease, as well as patients who had previously undergone an allogeneic stem cell transplant were excluded from the trial.
Patients were randomized to either the omidubicel or comparator arm, and the baseline demographics and characteristics were balanced between the 2 arms.
Of patients who were able to be transplanted, as per protocol, successful neutrophil engraftment, measured at day 42, was achieved by 96% of patients in the omidubicel arm versus 88% in the control arm.
These findings are consistent with those from a phase I/II trial (NCT01816230) in which the median time to neutrophil recovery was 11.5 days (95% CI, 9-14 days) with omidubicel in 36 patients with hematologic malignancies undergoing transplant. This was then compared with a group of 146 patients who received standard umbilical cord blood transplant from the Center for International Blood and Marrow Transplant Research (CIBMTR), in which the median time to neutrophil recovery was 21 days (95% CI, 20-23 days) (P <.001).2
The median time to platelet recovery in the omidubicel group was 34 days (95% CI, 32-42 days) versus 46 days (95% CI, 42-50 days) in the CIBMTR group (P <.001).
Forty-four percent of patients in the omidubicel group developed grade 2 to 4 graft-versus-host disease (GVHD) at day 100 compared with 56% of patients in the CIBMTR comparator group (HR, 0.7; P = .20). At 2 years, the rate of chronic GVHD was 40% in the omidubicel group versus 30% in the CIBMTR group, and the rate of moderate to severe chronic GVHD was 10% in both groups at 2 years.
The rates of disease-free survival and overall survival were similar between the 2 groups at 2 years, even when adjusted for both age and disease-risk index.
The most common adverse event attributed to omidubicel was hypertension.
Previously, the FDA granted omidubicel with a Breakthrough Therapy Designation for use as a bone marrow transplant graft.
“Omidubicel is the first bone marrow transplant product to receive Breakthrough Therapy Designation from the US Food and Drug Administration and has the potential to be the first FDA-approved bone marrow transplant graft. We are very pleased with the results of the phase III data reported today, which move us one step closer toward bringing potentially curative therapies to patients. We expect to begin to submit our biologics license application for omidubicel to the FDA on a rolling basis in the fourth quarter of this year,” Julian Adams, PhD, chief executive officer of Gamida Cell, said in a statement.
1. Gamida Cell announces positive topline data from phase 3 clinical study of omidubicel in patients with high-risk hematologic malignancies [news release]. Boston, MA: Gamida Cell Ltd.; May 12, 2020. https://bit.ly/2AnNx5d. Accessed May 12, 2020.
2. Horwitz ME, Wease S, Blackwell B, Valcarcel D, et al. Phase I/II study of stem-cell transplantation using a single cord blood unit expanded ex vivo with nicotinamide. J Clin Oncol. 2018;37(5):367-374. doi: 10.1200/JCO.18.00053