Bone Marrow Deficiency

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Bone marrow deficiency refers to a condition in which the hematopoietic stem cells in the bone marrow fail to produce enough, or produce abnormal, red blood cells, white blood cells and platelets. Hematopoietic cell transplantation (HCT), the transplantation of multipotent hematopoietic cells, is a standard treatment in various malignant and non-malignant conditions. Transplant patients are subject to numerous complications which require extensive care and monitoring, and in some cases intensive treatments.

Poor graft function is a life-threatening complication for patients undergoing HCT, affecting 5-27% of patients[i], and can lead to incomplete recovery of the hematopoietic system. It is characterized by severe and persistent blood cell deficiency of at least two blood cell types (platelets, red and white blood cells). Current standard-of-care treatments do not develop satisfactory blood counts in some or all blood cell types. Consequently, patients are vulnerable to bleeding and recurrent infections, and require repeated costly transfusions of blood products, which only provide a short-term effect.

PLX-R18 may address this unmet need by stimulating the regeneration of damaged bone marrow to produce all blood cell types (white blood cells, red blood cells and platelets), where other treatments have proven ineffective.

Phase I Study Evaluating the Safety and Exploratory Efficacy of PLX-R18 in Patients with Incomplete Hematopoietic Recovery Following HCT in the U.S. and Israel (n=21)

The Phase I study is a multi-center, open-label, dose-escalating study to evaluate the safety of intramuscular (IM) injections of PLX-R18 cells to patients with incomplete hematopoietic recovery persisting for at least 3 months after HCT. 

Positive Phase I Results

Pluristem reported results from 21 patients in the U.S. and Israel enrolled into the study. The patients were at least three months after the HCT procedure, and had low blood counts in at least one blood cell type. Patients were assigned to one of three treatment arms: 1 million cells/kg, 2 million cells/kg or 4 million cells/kg. Each patient received two treatments of the assigned dose.

Data at 12-month Follow-Up Demonstrated:

  • PLX-R18 was well-tolerated with a favorable safety profile.
  • Reduced mortality from 29% to 18%
  • Increase in all three blood cell types with platelets (p<0.001), hemoglobin (p=0.01) and neutrophils (p=0.15) levels increasing, enduring up to 12 months
  • Decreased mean number of transfused units from a monthly 5.09 to 0.55 for platelets (p=0.045) and 2.91 to 0 for red blood cells (p=0.0005) at 12 months

These results open up the potential to develop therapies that address a variety of hematological deficiencies.

 

This is Pluristem’s first study to evaluate the safety and exploratory efficacy of PLX-R18 in humans.  The study supports previous preclinical results, conducted via the U.S. Food and Drug Administration’s (FDA) Animal Rule in collaboration with the U.S. National Institutes of Health (NIH), in which PLX-R18 was found effective in treating bone marrow failure from Acute Radiation Syndrome (ARS).

PLX-R18’s Mechanism of Action

Watch Dr. Nitsan Halevy, Pluristem’s Chief Medical Officer, and Dr. Racheli Ofir, Pluristem’s VP of Research & Intellectual Property, discuss these Phase I hematology program results and explain more about how PLX-R18’s mechanism of action affects blood cell regeneration.

FDA Orphan Drug Designation & Patents

PLX-R18 cell therapy was granted an Orphan Drug Designation by the FDA for the treatment of graft failure and incomplete hematopoietic recovery following HCT. The Orphan Drug Act provides for granting special status to a drug or biological product, to treat a rare disease or condition. The benefits of achieving Orphan Drug Designation include close guidance by the FDA, which may accelerate the path to potential marketing approval, orphan drug grants, tax credits, and 7-year market exclusivity upon marketing approval.

Pluristem was also granted a patent titled “Methods for Treating Radiation or Chemical Injury” for PLX-R18 cell therapy. This important patent, issued by the European Patent Office, expands the company’s IP assets to include a new set of indications related to the bone marrow’s inability to produce blood cells, such as acute radiation syndrome (ARS), autoimmune diseases such as aplastic anemia, genetic disorders, and side effects from chemotherapy, radiation and other treatments.

* Data from the 6-month follow-up is available for 14 of the 21 treated patients: one patient was terminated early, three patients missed the 6-month visit and three died prior to the 6-month visit (two fatal events in the 2 million cell dose, and one fatal event in the 4 million cell dose). All fatal events in the study were considered unrelated to the study treatment. Mortality rates were in line with publicly available information[1],[2],[3],[4],[5].

References:

[1] Gao, F. et al. 2020. Eltrombopag treatment promotes platelet recovery and reduces platelet transfusion for patients with post-transplantation thrombocytopenia. Annals of Hematology. 99:2679–2687. (2020)

[2] Halahleh, K. et al. 2021. Therapy of posttransplant poor graft function with eltrombopag. Bone Marrow Transplantation. 56:4-6. 

[3] Tang, C. et al. 2018. Successful treatment of secondary poor graft function post allogeneic hematopoietic stem cell transplantation with eltrombopag. J Hematol Oncol. Aug 16;11(1):103.

[4] Sun, Y. et al. 2015. The incidence, risk factors, and outcomes of primary poor graft function after unmanipulated haploidentical stem cell transplantation. Annals of Hematology 941699–1705.

[5] Zhao, Y et al. 2019. Incidence, Risk Factors, and Outcomes of Primary Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. Sep;25(9):1898-1907.