A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part II. Countermeasures for limited indications, internalized radionuclides, emesis, late effects, and agents demonstrating efficacy in large animals with or without FDA IND status

Abstract

The dearth of FDA-approved radiation countermeasures has prompted intensified research for a new generation of radiation countermeasures. A number of promising radiation countermeasures are currently moving forward with continued support and effort by both governmental agencies and by publicly and privately held pharmaceutical companies. There is a limited number of countermeasures which are progressing well following the Animal Rule and may get approved in the near future, thus serving to close the gap of this critically important, unmet radiobiomedical need.

Pharmacological management of ionizing radiation injuries: current and prospective agents and targeted organ systems

“…In addition, there are four agents approved as blocker/binder/ chelator for internalized radionuclides. Furthermore, there are a few agents which have been approved for limited indications [2,44,45].…”

“…Mode of action The abovementioned agents have been discussed in recent reviews [44,45]. There may be additional agents with FDA IND for ARS but such agents are not in public knowledge.…”

“…Amifostine is the only agent classified as a cytoprotectant and is approved for narrow clinical indications associated with radiotherapy and chemotherapy [76,77]. Furthermore, there are several cytokines and growth factors (palifermin (keratinocyte growth factor), erythropoietin (Epoetin/Epogen/ Procrit/Darbepoetin/Aransep), IL-3, IL-11 (Oprelvekin)) which have been approved by the FDA for limited indications (mostly cancer patients receiving chemotherapy and/or radiotherapy) [2,44,45].…”

“…Though limited agents have received FDA approval, a large number of countermeasures are under development as radioprotectors, mitigators, and therapeutics for radiation injuries [2,44,45].…”

The efficacy and safety of amifostine for the acute radiation syndrome

“…Such agents are divided into three classes: radioprotectors (prophylaxis), radiomitigators (to be used soon after exposure), and therapeutics [5]. There are several radiation countermeasures under development that have been considered safe and efficacious to be used as radioprotective agents for radiological/nuclear events; however, they have not yet received FDA approval and need more studies [6][7][8][9][10]. All three currently FDAapproved radiation countermeasures (Neupogen/filgrastim/granulocyte colony-stimulating factor (G-CSF), Neulasta/pegfilgrastim/ G-CSF, and Leukine/sargramostim/granulocyte-macrophage colony-stimulating factor (GM-CSF)) are defined as radiomitigators.…”