Omidubicel: Ronit Simantov Phase 3 Results [2022] Blood Cancers

What is omidubicel and can this improve clinical outcomes? - Omidubicel is was developed as a stem cell source for use in patients who need an allogeneic stem cell transplant(stem cell transplantation). And these are patients with hematological malignancies like leukemia, myelodysplastic syndrome, lymphoma, and other diseases. Patients receiving omidubicel is derived from umbilical cord blood, which was identified years ago as a source of hematopoietic stem cells.

But because of the size of (umbilical) cord blood, it often contains too few cells to serve as an effective transplant source. Omidubicel leverages allogeneic cells, NAM technology to enhance the number of cells as well as the functionality of. What we do using the NAM technologies expand and metabolically modulate the stem cells with growth factors and other ingredients to maintain the cells active phenotype and to enhance the potency of cells. So the NAM Technologies use to create a stem cell source that we are now is now known as own. Explained Ronit Simantov, MD

4 Key Statistics on Ombidubicel

1. In mouse models of EMT6 breast cancer, CT26 colon cancer, and B16F10 melanoma, the efficacy of intratumoral injection of 108 PFU CodaLytic 3x/week for up to 12 doses as a monotherapy and/or in combination with systemic anti-PD-1 checkpoint blockade was evaluated.

2. Multiple oncolytic viruses have been shown to induce favorable changes in the tumor microenvironment (TME) by increasing immune cell infiltration and activating stimulatory immune responses, which ultimately support anti-tumor immunity induction and efficacy.

3. CodaLytic monotherapy resulted in substantial tumor growth inhibition (TGI) across tumor models, including 76% TGI in EMT6 with moderate, immunologically active infiltration [1] and 69% TGI in poorly infiltrated, PD-1-resistant B16F10 melanoma.

4. CodaLytic therapy generated beneficial alterations in numerous mouse tumor models independent of their intrinsic immune contexture and sensitized B16F10 melanomas to PD-1 inhibition.

Omidubicel VS Current Standard Of Care For Patients With Blood Cancer? And How Can Omidubicel Give Patients Clinical Benefit?

Patients treated with hematologic malignancies like leukemia and MDs and some lymphomas may be treated with an allogeneic stem cell transplant (stem cell transplantation). The transplant will replace the patient's own diseased bone marrow and can serve over time to eradicate any lasting tumor cells. Patients need to have a source of transplant that matches their own cells in some way in order for the stem cell transplantation to be effective. There are a number of standard of care donor sources for patients with these diseases who receive a transplant.

The donor sources include match related donors who are relatives of patients, and only about 25% of patients actually have a match related donor that's able to donate. There's zen matched unrelated donors and mismatched unrelated donors that are found in the registries for patients who will need a transplant. And strangers who donate transplant who donate stem cells will be able to serve as donors but not everybody has a match through the unrelated donor registries. A newly device, stem cell transplant source is haploidentical or half matched stem cells, which are used in many patients, but will require additional treatment to prevent graft versus host disease in these patients.

And then finally, standard (umbilical) cord blood has been used for patients for many years. It is a smaller stem cell source (NK cells) and has been used more successfully in pediatric patients. But it is considered quite a good source of stem cells, and that's what Omidubicel leverages by taking standard (umbilical) cord blood and now creating Omidubicel using our NAM technology. Said Ronit Simantov, MD

What Is The Omidubicel Clinical Trials' Design?

The Omidubicel phase III randomly assigned clinical trial that was conducted globally. And the patients who entered the trial were those who needed a transplant. Patients with hematologic malignancies like leukemia and lymphoma who did not have a standard stem cell source. They were not able to find a match in the system. Patients were then randomly assigned to be transplanted either with Omidubicel or with standard cord blood. And patients in the standard cord blood arm could receive either one or two units of standard cord blood because of the size of the (umbilical) cord blood stem cell units. Patients (median follow up) were followed after their transplant and evaluated for the primary end point of neutrophil graft, as well as a number of secondary endpoints and safety.

What Are The Inclusions and Exclusions Criteria For The Omidubicel Clinical Trial?

Patients were ages 12 to 65 with high risk hematologic malignancies. For whom it was appropriate to have a transplant. Patients had to be healthy enough to undergo the transplant and were otherwise enrolled if they did not have a standard match in the system and needed an alternative stem cell transplant source.

What Were Some Of The Key Data Points Of The Omidubicel Clinical Trial?

What oncologists need to know is that the primary endpoint for this trial was neutrophil engraftment. Neutrophil engraftment is a very key point in the recovery of patients after a bone marrow transplant (in bone marrow transplant research). Patients receive a conditioning regimen that renders them highly pancytopenic, meaning they have absolutely zero counts, and the lack of time to neutrophil engraftment in these patients makes them susceptible to infections and other complications. So the primary endpoint of this study was the time it took for neutrophil (platelet) engraftment, and it was defined very precisely as three days in a row in which their neutrophil count was 500 cells per microliter or more. In order to make the measurement as objective and as quantitative as possible, that figure and that accepted criterion were chosen. That makes it very easy to measure and a good endpoint for a phase 3 clinical trial (of omidubicel) because of its objectivity and ease of measurement.

Other endpoints were supportive of the clinical significance of the Nero graft, and they included infections and the time that patients spent in the hospital, and all of those endpoints altogether really gave us a picture of the comparison of Omidubicel outcomes to outcomes with standard core. Explained Ronit Simantov, MD.

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Have The Primary Endpoints Been Met In The Omidubicel Clinical Trial? And What Do The Results Suggest?

The study met its primary endpoint of neutrophil recovery in patients who were transplanted with Omidubicel. The patients who were transplanted with Omidubicel recovered their neutrophils in 12 days, omidubicel compared to 22 days for the control arm (omidubicel arm). This was statistically significant, with a P value of less than 0.001, and also highly clinically significant because neutrophil recovery is such a key outcome in the recovery from transplant.

There were three formal, pre-specified secondary endpoints, including faster platelet recovery. The time between the first bacterial or invasive fungal infections, and the time that patients were days alive and out of the hospital.

In terms of platelet recovery, the recovery occurred faster in patients who were transplanted with Omidubicel. By 42 days, 55% versus 35% of patients had recovered their platelets, and that was statistically significant. In terms of the time to the first grade two or three bacterial or invasive fungal infection, 37% of patients who were randomized to Omidubicel had a bacterial fungal infection versus 57% in patients transplanted with cord blood, and the P value was 0.027.

This was statistically significant and, of course, quite clinically significant as well. And then, in terms of the third secondary endpoint, this was the number of days alive and out of the hospital in the first hundred days after transplant. Patients who received transplants with Omidubicel spent more time outside of the hospital, with a median of 61 days versus 48 days for the control, and a P value of 0.00. Ronit Simantov, MD

Were There Any Clinical Results That Are Statistically Significant?

All the primary and all secondary endpoints were statistically significant for transplantation in patients with leukemia, lymphoma, and MDs in the phase 3 study.

Final Thoughts On The Omidubicel Clinical Trial

Omidubicel is a potential graft source for patients who are in need of transplant and has the potential, if FDA approved, to increase access to transplant for more patients, it's easier to match patients for Omidubicel than it is to find a match on the donor registry.

Patients who are minorities or of diverse backgrounds have a higher probability of getting a match from the cord blood registry than from the adult donor registry for adult patients. And this will, the approve potential approval of Omidubicel will potentially increase access to patients and also with its decrease in nutritional time to neutrophil recovery has a potential to improve outcomes in patients based on comparisons with existing transplant sources. Concluded Ronit Simantov, MD

Ronit Simantov, MD - About The Author, Credentials, and Affiliations

Ronit Simantov, MD, joined Gamida Cell's leadership team in July 2017 as Chief Medical Officer, bringing with him over 20 years of experience in hematology and cancer research, development, registration, and product launch. Prior to joining Gamida Cell, Ronit was Head of Oncology Global Medical Affairs at Pfizer, where she oversaw multiple programs, including Sutent® (sunitinib), Inlyta ® (axitinib), Ibrance® (palbociclib), Bosulif® (bosulif), and Xalkori ®. Previously, as Vice President of Clinical Research at OSI Pharmaceuticals, Ronit oversaw phase 1-3 clinical trials. She was also the Chief Medical Officer at CuraGen Corporation, which was acquired by Celldex, where she oversaw the development of small molecules and antibody-drug conjugates. Ronit directed the phase 3 study of Nexavar® (sorafenib) at Bayer HealthCare Pharmaceuticals, which resulted in the first approval of a tyrosine kinase inhibitor for renal cell carcinoma. Ronit spent seven years on the faculty at Weill Medical College at Cornell University, where she supervised the fellowship program and conducted angiogenesis and vascular biology research, prior to entering the private sector. She has authored approximately 40 manuscripts that have been peer-reviewed.

Ronit holds a doctorate in medicine from the New York University School of Medicine and a bachelor's degree in science from Johns Hopkins University. She did her internal medicine residency at New York Hospital Cornell Medical Center and her hematology and medical oncology fellowship at Weill Cornell Medicine.

Gamida Cell - About the Company

Gamida Cell is in the forefront of developing a diversified immunotherapy pipeline of potentially curative advanced cell therapy candidates for patients with solid tumor and blood malignancies, as well as other critical blood illnesses. We deploy a patented expansion platform utilizing the features of NAM (enabled cell therapies) to allogeneic cell sources, such as cord blood-derived cells and NK cells, to generate therapeutic candidates with the potential to revolutionize standards of care. These include omidubicel, an investigational product with the potential to be a life-saving alternative for patients requiring a bone marrow transplant product, and a line of modified and unmodified NAM-enabled NK cells aimed at solid tumor and hematological malignancies.