Omidubicel Meets All Secondary End Points of Phase 3 Trial in Hematologic Malignancies

Mitchell Horwitz, MD

The investigational advanced cell therapy omidubicel resulted in rapid platelet engraftment and reduced the number of infections and hospitalizations in patients with high-risk hematologic malignancies, meeting all 3 secondary end points of a phase 3 trial (NCT02730299), according to an announcement from Gamida Cell Ltd.¹

Specifically, the prespecified secondary end points included the proportion of patients who achieved platelet engraftment by day 42, the proportion of patients with grade 2 or 3 bacterial or invasive fungal infections within the first 100 days after transplant, and the number of days alive and out of the hospital within the first 100 days after transplant.

For all 3 secondary end points, patients who received treatment with omidubicel experienced a statistically significant improvement compared with those in the comparator arm comprised of standard umbilical cord blood transplant. The company plans to present the full results at an upcoming medical conference later this year; they also anticipate initiating a biologics license application submission for the product in this setting in the fourth quarter of 2020.

“These data, obtained in a global, randomized, multi-institutional setting, could represent an important step forward in the field,” Mitchell Horwitz, MD, principal investigator and professor of medicine at the Duke Cancer Institute, stated in a press release. “In addition to more rapid platelet engraftment, a key step toward recovery, reducing infections and hospitalization are considered meaningful patient outcomes and have the potential to provide substantial value for patients, their families, and the healthcare system.”

Previously, in May 2020, omidubicel was found to have met the primary end point of the trial with regard to time to neutrophil engraftment in patients with high-risk hematologic malignancies who were undergoing a bone marrow transplant.² The median time to neutrophil engraftment was 12 days (95% CI, 10-15) in the omidubicel arm versus 22 days (95% CI, 19-25) in the control arm (P <.001).

A total of 125 patients were included in the intent-to-treat analysis of the multicenter, international, open-label phase 3 trial. Participants ranged in age from 12 years to 65 years; they had acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome, or lymphoma. All patients had high-risk disease and were undergoing a bone marrow transplant.

In the trial, participants were randomized to receive wither omidubicel or standard umbilical cord blood transplant. The primary end point of the trial was neutrophil engraftment. Additional results showed that of those who received transplant in accordance with the study protocol, successful neutrophil engraftment was reported in 96% of those in the investigational arm versus 88% of those in the control arm.

In an earlier phase 1/2 study, investigators examined omidubicel in 36 patients with advanced hematologic malignancies. In comparison with a cohort of 146 patients who received standard umbilical cord blood per the Center for International Blood and Bone Marrow Transplant Research, omidubicel was found to lead to faster neutrophil engraftment. The median time to engraftment in the investigational and control arms was 11.5 days (95% CI, 9-14) versus 21 days (95% CI, 20-23), respectively (P <.001).

“The totality of these data strengthen my belief that omidubicel has the potential to be a graft source for any patient who does not have access to a matched related donor and could help make stem cell transplantation more accessible and more successful for patients with lethal blood cancers,” added Horwitz.

In October 2016, omidubicel was the first bone marrow transplant product to receive a breakthrough therapy designation from the FDA.³ If approved down the line, the agent could represent the first engineered bone marrow transplant graft to obtain regulatory approval, according to Gamida Cell Ltd.

Omidubicel is also under exploration in a phase 1/2 trial (NCT03173937) in patients with severe aplastic anemia.⁴ A new drug application for the aplastic anemia indication is filed under the brand name Cordin; this is the same investigational candidate as omidubicel.

References

1. Gamida Cell announces positive topline data on secondary endpoints from phase 3 clinical study of omidubicel in patients with hematologic malignancies. News release. Gamida Cell Ltd. October 6, 2020. Accessed October 6, 2020. https://bit.ly/3ljRlqh.
2. Gamida Cell announces positive topline data from phase 3 clinical study of omidubicel in patients with high-risk hematologic malignancies. News release. May 12, 2020. Accessed October 6, 2020. https://bit.ly/3lkoT7w.
3. Gamida Cell receives FDA breakthrough therapy designation for NiCord. News release. October 11, 2016. Accessed October 6, 2020. https://bit.ly/2Sw7XyF.
4. Unrelated umbilical cord blood transplantation for severe aplastic anemia and hypo-plastic MDS using CordIn(TM), umbilical cord blood-derived ex vivo expanded stem and progenitor cells to expedite engraftment and improve transplant outcome. ClinicalTrials.gov. Updated June 5, 2020. Accessed October 6, 2020. https://clinicaltrials.gov/ct2/show/NCT03173937​