Studies of PLX-R18 in ARS
Acute Radiation Syndrome (ARS) involves severe, potentially lethal damage to the bone marrow’s ability to produce blood cells and platelets, as well as to other systems and organs. Severe damage to bone marrow makes victims vulnerable to life-threatening hemorrhage, infection and anemia. As efficacy trials are not permitted in humans for this indication, studies in large animal models are needed to evaluate dosing for Pluristem’s PLX-R18 as a medical countermeasure in the treatment of the hematologic aspects of ARS.
Several pre-clinical studies of PLX-R18 as a potential treatment of the hematologic syndrome of Acute Radiation Syndrome (ARS) were completed under the support of the National Institute of Allergy and Infectious Diseases (NIAID), a part of the U.S. National Institutes of Health (NIH). NIAID studies showed that PLX-R18 administration resulted in a statistically significant improvement in the recovery of blood cell production in small animals exposed to high levels of radiation, and demonstrated the treatment’s mechanism of action. The NIAID’s first study of PLX-R18 showed a substantial, statistically significant improvement in the survival of irradiated rodents treated with PLX-R18 versus a control group.
Other studies of PLX-R18, in both ARS and other hematological indications, were conducted in conjunction with Charité Universitätsmedizin Berlin Institute of Medical Immunology, the Berlin-Brandenburg Center for Regenerative Therapies, Case Western Reserve University, Hadassah Hebrew University Medical Center, and Indiana University; the NIAID provided support for the research conducted at Indiana University.
Collaboration on ARS with U.S. Government (NIAID)
A Phase I and II-equivalent trials via the U.S. Food and Drug Administration (FDA) Animal Rule Pathway were conducted by the NIAID. The study was designed to assess the safety and efficacy of PLX-R18 following intramuscular injection into irradiated and non-irradiated NHPs. Efficacy measures included survival as well as level of bone marrow function, which is affected by exposure to high levels of radiation as may occur in a nuclear accident or attack.
Study results showed all doses of PLX-R18 improved survival rates compared to control groups. The Phase II-equivalent study also demonstrated a trend towards enhanced neutrophil and lymphocyte recovery. Safety data showed that PLX-R18 cells did not affect non-irradiated animals. This indicates that individuals can be treated without determining their degree of exposure to radiation.
Additional data from the study focuses on exposure to lower radiation levels. The findings suggest that even though low radiation exposure is not lethal, it can lead to serious hematological deficiencies and to long-term health problems that result from such damage.
Once the optimal dose is determined in large animals, a pivotal trial could be conducted to support submission of a Biologics License Application (BLA) for PLX-R18 for this indication under the FDA Animal Rule regulatory pathway.
Following the positive study results, conducted by the NIH, Pluristem was approached by the U.S. Department of Defense’s (DOD) to conduct studies to examine the effectiveness of PLX-R18 as a treatment for ARS prior to, and within the first 24 hours of exposure to radiation. The study will be conducted in parallel to the ongoing project with the NIH and in accordance with the FDA Animal Rule pathway.
PLX-R18 cell therapy was granted an orphan drug designation by the FDA for the treatment of ARS. 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.
We also have a memorandum of understanding with Fukushima Medical University, Fukushima Global Medical Science Center, in Japan, to collaborate on the development of PLX-R18 cells for the treatment of ARS, and as an adjunct to radiotherapy in cancer patients.
For more information regarding ARS press here.