Many governments, including the U.S. and Japan, are well aware of the dangers to their populations of exposure to high levels of radiation from nuclear accidents or dirty bomb attacks. Whereas Japan’s population was recently exposed at Fukushima following the tsunami of 2011, the U.S. Department of Defense has been stockpiling acute radiation syndrome (ARS) countermeasures as a precaution for many years.
The recent escalation of tensions between North Korea and the U.S. may give the American government cause to up its investment in ARS antidotes. During a military parade on April 15th, North Korea displayed weapons including an intercontinental ballistic missile (ICBM) that could be capable of reaching the U.S. ARS may have just become a larger threat to health than it was just a few weeks ago.
Caused by exposure to a high doses of ionizing radiation over a short period of time, such as could occur after the meltdown of a nuclear reactor or the detonation of a “dirty bomb”, ARS can cause potentially lethal damage to the gastrointestinal tract, lung, skin, blood and bone marrow, as well as other systems.
Pluristem Therapeutics (NASDAQ:PSTI) is working with both the U.S. and Japan to help provide potentially lifesaving cell therapies to counteract the damage from overexposure to radiation. The U.S. National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID) is completing dose-selection trials for Pluristem’s PLX-R18 cell therapy in the treatment of the hematologic syndrome of ARS. This is characterized by severe decreases in the numbers of platelets and red and white blood cells due to the destruction of the bone marrow progenitor cells which produce these cells.
In the hematologic syndrome of ARS, low numbers of these cells can result in uncontrollable bleeding, anemia, severe infection and death. Without a functioning bone marrow patients require multiple transfusions on an ongoing basis, although supplies of platelets and red cells can be limited and there can be negative side effects from serial transfusions.
When the optimal dosage is defined, this data will potentially serve as the basis for a final pivotal trial in large animals, which will provide the evidence of efficacy for approval under the FDA’s Animal Rule. The pivotal trial would evaluate the therapeutic response to PLX-R18 up to approximately 60 days following dosage, and such an approval would enable the U.S. government to purchase and stockpile PLX-R18, for use in the case of a nuclear catastrophe.
In a similar deal, the U.S. Biomedical Advanced Research and Development Authority (BARDA), the U.S. Department of Health and Human Services’ division responsible for countermeasures against bioterrorism, ordered more than $150 million worth of Neupogen®, which was approved by the FDA in 2015. It was the first drug approved by the FDA for the treatment of the hematopoietic syndrome of ARS, also known as H-ARS.
In 2016, BARDA made two more purchases to add to its stockpile. Leukocyte growth factor products, Neulasta from Amgen and Leukine from Sanofi, were purchased in quantities totaling $37.7 million and $37.6 million. Moreover, a $2.8 billion 5-year budget has been appropriated for Project BioShield for 2013 – 2018 for similar purchases.
PLX-R18 is particularly well suited for stockpiling. An off-the-shelf cell therapy, requiring no tissue matching, it has a shelf life of three years. Preclinical data show PLX-R18 cells secrete a range of specific proteins that trigger the regeneration of bone marrow hematopoietic stem cells, thereby supporting the recovery of blood cell production after exposure to life threating levels of radiation. It is also the only potential ARS antidote that can boost production of all three blood components: white blood cells, red blood cells, and platelets.
In Japan, Pluristem has a memorandum of understanding with Fukushima Medical University, Fukushima Global Medical Science Center, to collaborate on the development of PLX-R18 cells for the treatment of ARS, and as an adjunct to radiotherapy in cancer patients. PLX-R18 cells will be studied primarily as a potential treatment for radiation-induced damage to the skin, lungs and gastrointestinal tract. Preclinical models of radiation damage will be developed, and used in the trials. Pluristem will contribute PLX-R18 cells and scientific knowledge, while Fukushima Medical University will conduct the studies, and provide the required resources.
Pluristem’s CEO, Zami Aberman commented on the collaboration, “We anticipate that our work with Fukushima Medical University, Fukushima Global Medical Science Center will help to maintain the health of those involved in decommissioning the Fukushima reactors; the decommissioning process is estimated to take about 40 years. We hope that this collaboration can advance efforts to safeguard populations around the world from illness related to radiation exposure.”
Further advancing its ARS program, Pluristem recently appointed Dr. Arik Eisenkraft to the newly created position of Director, Homeland Security Products at Pluristem. Lt. Colonel Dr. Eisenkraft was formerly Head of Medicine Branch for the Israeli Ministry of Defense where he led clinical studies and product development for chemical, biological, radiological, and nuclear (CBRN) countermeasures. As Chief of Medical Section for the Israeli Defense Forces’ (IDF) Medical Corps, he headed up the nuclear, biological, and chemical (NBC) Protection Division, leading national R&D programs of medical countermeasures, working closely with governmental agencies, the IDF, and the Israeli Ministry of Health.
Pluristem is expecting data from the NIH dose finding study for PLX-R18 in the treatment of ARS in the first half of 2017.