A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part III. Countermeasures under early stages of development along with ‘standard of care’ medicinal and procedures not requiring regulatory approval for use

Abstract

Despite the significant progress that has been made in this area during the last several years, additional effort is needed in order to push promising new agents, currently under development, through the regulatory pipeline. This pipeline for new promising drugs appears to be unreasonably slow and cumbersome; possible reasons for this inefficiency are briefly discussed. Significant and continued effort needs to be afforded to this research and development area, as to date, there is no approved radioprotector that can be administered prior to high dose radiation exposure. This represents a very significant, unmet medical need and a significant security issue. A large number of agents with potential to interact with different biological targets are under development. In the next few years, several additional radiation countermeasures will likely receive Food and Drug Administration approval, increasing treatment options for victims exposed to unwanted ionizing irradiation.

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.…”