FDA Approves Omisirge Cell Therapy to Reduce Infection Risk in Patients with Hematologic Malignancies

The U.S Food and Drug Administration (FDA) has approved Omisirge (omidubicel-onlv) by Gamida Cell Ltd, a modified allogeneic hematopoietic stem cell therapy to hasten neutrophil recovery and reduce infection risks in transplant recipients.

Omisirge (omidubicel-onlv) is indicated for use in adults or children above 12 years old with hematologic malignancies planned for umbilical cord blood transplantation after myeloablative conditioning regimens.

Clinical Landscape of Blood Cancers

Hematologic malignancies are cancers that affect the blood, bone marrow, and lymph nodes, and they are characterized by the unregulated proliferation of blood-forming cells. These include the various types of leukaemia (acute lymphocytic (ALL), chronic lymphocytic (CLL), acute myeloid (AML), chronic myeloid (CML)), myeloma, and lymphoma (Hodgkin’s and non-Hodgkin’s (NHL)) [1,2]. In Southeast Asia, the incidence of hematologic malignancies is predicted to increase by 50% from 2012 to 2030 [3]. Hematologic malignancies may initially present with mild symptoms such as fatigue or itchy skin [3]. However, as they progress and infiltrate various tissues such as the lymph nodes, skin, liver, spleen, kidney, and central nervous system [2], they can cause more serious events such as bone and joint pain, infections, weight loss and individuals are more easily bruised or bleed [3].

Present Treatment Options For Blood Cancers

Depending on individual clinical progressions, treatment types may include a combination of the following: hematopoietic stem cell transplant (HSCT), chemotherapy, chimeric antigen receptor (CAR) T cell therapy, immunotherapy, radiation therapy and targeted therapy [4].

HSCT involves intravenous infusion of hematopoietic stem cells to restore blood cell production in patients with impaired bone marrow or immune systems. The cells can come from patients themselves (autologous transplant) or from a donor (allogeneic transplant) [5]. The cells can be sourced from the bone marrow, peripheral blood, umbilical cord blood or fetal liver [5]. In allogeneic HSCT, the hematopoietic stem and progenitor cells from the donor are intravenously infused and grafted into the recipient’s bone marrow. The donor immune effector cells then interact with the recipient’s immune cells to eventually reach a stable chimeric state and restore functional B lymphocytes, T lymphocytes, natural killer cells and a stable graft-vs-tumour (GvT) effect [6].

Preparation for HSCT typically involves prior high-dose chemotherapy with or without radiation to prevent graft rejection and allow donor cell engraftment during infusion [7]. However, this immunosuppression reduces immune cells count and puts patients at risk of potentially severe opportunistic infections. 

Omisirge: Combating Chemotherapy-Related Infections  [8]

FDA-approved Omisirge (omidubicel-onlv) is touted to hasten neutrophil recovery and reduce the risk of infections in patients with hematologic malignancies planned for umbilical cord blood transplantation following a myeloablative conditioning regimen (radiation or chemotherapy treatment) [9].

Omisirge is composed of human allogeneic stem cells derived from umbilical cord blood that has been processed and cultured with nicotinamide [9]. It is currently authorized for use in adults and paediatrics over the age of 12 years [9].

In a multicenter, open-label, randomized trial (NCT02730299), known as Study P0501, the efficacy and safety of Omisirge were evaluated [10]. A total of 52 patients were transplanted with Omisirge, while 56 received umbilical cord blood (UCB) transplants. Patients were given myeloablative preparative regimens prior to the transplant and prophylaxis against graft versus host disease (GvHD) with either tacrolimus or cyclosporin and mycophenolate mofetil. The median duration of follow-up was 14 months, with a range of 1 to 19 months. The primary endpoint of the study was the duration of time required for neutrophil engraftment.

Efficacy data on Omisirge

Among the patients who were treated with Omisirge, 87% achieved neutrophil recovery within a median of 12 days after therapy, while 83% of the UCB-treated patients required a median of 22 days to achieve neutrophil recovery. In the 100 days following transplantation, bacterial or fungal infections were observed in 39% of the Omisirge-treated patients, compared to 60% of the UCB-treated patients.

Omisirge treatment resulted in a shortened duration for hematopoietic recovery and reduced incidence of early transplant-related complications when compared to standard UCB transplantation.

Safety data on Omisirge

56% and 71% experience infusion reactions on the arm for Omisirge and UCB arms respectively. Fatal adverse reactions were experienced by 17% of the patients who received Omisirge, such as infections (6%), GvHD (6%), veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) (2%), thrombotic thrombocytopenic purpura (TTP)/thrombotic microangiopathy (TMA) (2%), and pulmonary haemorrhage (2%). In contrast, fatal adverse reactions were reported in 29% of the UCB-treated patients [10].

Study P0501 [8]

*Adverse reactions included infections/sepsis, GvHD, veno-occlusive disease/sinusoidal obstruction, thrombotic thrombocytopenic purpura/thrombotic microangiopathy, pulmonary haemorrhage, respiratory disorders

Takeaway

The Omisirge application received Priority Review, Breakthrough Therapy and Orphan designations. The FDA has also granted regular approval of Omisirge to Gamida Cell Ltd.

References:

1. Sanjeev Banerjee, Mansi A. Parasramka, Shivani B. Paruthy, Chapter 15 – Garcinol: Preclinical Perspective Underpinning Chemo- and Radiosensitization of Cancer, In Cancer Sensitizing Agents for Chemotherapy, Role of Nutraceuticals in Cancer Chemosensitization, Academic Press, Volume 2, 2018,Pages 297-324, https://doi.org/10.1016/B978-0-12-812373-7.00015-2.
2. DiPiro J.T., & Talbert R.L., & Yee G.C., & Matzke G.R., & Wells B.G., & Posey L(Eds.), (2017). Pharmacotherapy: A Pathophysiologic Approach, 10e. McGraw Hill. https://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=146028752
3. Janssen Pharmaceutical Companies of Johnson & Johnson. Make Blood Cancer Visible, Asia Pacifc Report. 2018. Available at: https://www.janssen.com/apac/news-center/health-policy-and-advocacy/make-blood-cancer-visible
4. Abramson Cancer Centre, Penn Medicine. Blood Cancer (Hematological Malignancies) Program. Available at: https://www.pennmedicine.org/cancer/navigating-cancer-care/programs-and-centers/hematological-malignancies-program (Accessed on 8 May, 2023).
5. Theodore Moore, M.D. (2023) Hematopoietic Stem Cell Transplantation (HSCT), Practice Essentials, Historical Background, Indications for HSCT. Medscape. Available at: https://emedicine.medscape.com/article/208954-overview (Accessed: May 8, 2023).
6. Hatzimichael E, Tuthill M. Hematopoietic stem cell transplantation. Stem Cells Cloning. 2010 Aug 26;3:105-17. doi: 10.2147/SCCAA.S6815. PMID: 24198516; PMCID: PMC3781735.
7. Philip Lanzkowsky, Chapter 29 – Hematopoietic Stem Cell Transplantation, Manual of Pediatric Hematology and Oncology (Fifth Edition), 2011,Pages 806-838, https://doi.org/10.1016/B978-0-12-375154-6.00029-X.
8. Horwitz ME, Stiff PJ, Cutler C, Brunstein C, Hanna R, Maziarz RT, Rezvani AR, Karris NA, McGuirk J, Valcarcel D, Schiller GJ, Lindemans CA, Hwang WYK, Koh LP, Keating A, Khaled Y, Hamerschlak N, Frankfurt O, Peled T, Segalovich I, Blackwell B, Wease S, Freedman LS, Galamidi-Cohen E, Sanz G. Omidubicel vs standard myeloablative umbilical cord blood transplantation: results of a phase 3 randomized study. Blood. 2021 Oct 21;138(16):1429-1440. doi: 10.1182/blood.2021011719. PMID: 34157093; PMCID: PMC9710469.
9. Office of the Commissioner (2023) FDA approves cell therapy for patients with blood cancers to reduce risk of infection following stem cell transplantation, U.S. Food and Drug Administration. FDA. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-cell-therapy-patients-blood-cancers-reduce-risk-infection-following-stem-cell (Accessed: May 8, 2023).
10. Gamida Cell Ltd (2023) Omisirge Product Information Leaflet, Omisirge Product Insert Leaflet. Available at: https://www.fda.gov/media/167202/download (Accessed: May 8, 2023).