Entolimod- A Medical Countermeasure to Reduce the Risk of Death Following Radiation Exposure
Abstract
This proposal, submitted by Cleveland BioLabs, Inc. (CBLI), describes the continued development of entolimod (CBLB502) as a medical radiation countermeasure (MRC). This proposal addresses Fiscal Year 2014 Peer Reviewed Medical Research Program (PRMRP) Topic Area "Illness Related to Radiation Exposure." Radiation to the human body can cause reductions in circulating infection-fighting cells and decreased blood-clotting ability, as well as ulcers and obstruction of the gastrointestinal tract. If the radiation dose is high, these medical conditions can lead to life-threatening infection, bleeding, and malnutrition that are often fatal. A terrorist-initiated radiation attack on the battlefield or in a major US city could cause the deaths of tens to hundreds of thousands of radiation-exposed victims. Such scenarios have encouraged the Department of Defense and other federal agencies to support development of MRCs that could be administered after irradiation to reduce the risk of radiation-related illness and death. Currently, no drug has been approved by the Food and Drug Administration (FDA) for use as an MRC. Entolimod is an investigational protein biologic drug that promotes tissue protection and regeneration. CBLI, a small biopharmaceutical company located in the United States, is developing entolimod as an MRC with the intent that it be approved by the FDA to reduce the risk of death following exposure to potentially lethal irradiation occurring as the result of a radiation disaster. For this use, entolimod could be given up to 25 hours after the radiation exposure. Because humans cannot be lethally irradiated to test the efficacy of an MRC, entolimod is being developed under the FDA Animal Rule. The Animal Rule provides a regulatory framework within which efficacy is documented in an appropriate animal model and safety is demonstrated in humans. Studies in both mice and in non-human primates (Rhesus monkeys) demonstrate that entolimod is highly effective when administered before or after lethal total body irradiation. In a randomized, placebo-controlled survival study, monkeys that had been exposed to high doses of radiation were given a single injection of placebo or of entolimod into a muscle at 25 hours after the irradiation. Entolimod provided a highly significant survival benefit, with survival improving from only 27.5% in the animals receiving placebo to 75% in animals receiving entolimod at the optimal dose. Entolimod also significantly improved the numbers of infection-fighting and clotting cells in the blood and reduced the severity of anemia. These benefits were particularly meaningful because the animals did not receive other supportive care such as blood transfusions, antibiotics, or intravenous fluids, most of which would likely not be available in a large-scale human radiation disaster. Based on the data from this and other monkey studies, as well as early clinical studies in healthy humans, the optimal entolimod dose in monkeys has been converted to an appropriate dose range in humans. As a final step toward FDA approval, CBLI now proposes to conduct a clinical study of entolimod in healthy adult humans to fully characterize the safety and pharmacology of the drug. This study would enlarge the entolimod safety database at the proposed dose range, provide more safety data in people with a range of body weights, generate information that might help confirm what doses could be used in all victims of a radiation disaster (adults and children), and help determine how best to use entolimod in an actual radiation emergency. This clinical trial is a randomized, placebo-controlled study of entolimod administered to healthy human volunteers. The participants will have a broad range of body weights in order to determine drug effects on a weight-adjusted basis. Eligible healthy volunteers will undergo medical examination and testing. They will then be divided into groups based on body weigh
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510570
Entities
People
- Langdon Miller
Organizations
- Cleveland BioLabs
- United States Army