PURPOSE: The acute radiation syndrome (ARS) represents a significant public health threat following nuclear exposure, with limited available medical countermeasures (MCMs). Imidazolyl ethanamide pentandioic acid (IEPA), a novel orally bioavailable small molecule, has demonstrated radioprotective effects in rodent models earlier. This study continues the investigation of IEPA as a MCM in non-human primates (NHP), a recognized large animal model for ARS. MATERIAL AND METHODS: Pharmacokinetic (PK) profiles and pharmacodynamic (PD) effects of IEPA were investigated in cynomolgus monkeys exposed to total-body irradiation (TBI) to assess its efficacy in reducing ARS-related mortality and mitigating radiation-induced myelosuppression (RIM). In addition to survival and clinical parameters, serum chemistry and bone marrow histology were analyzed. RESULTS: IEPA showed fast systemic absorption with linear, dose-dependent pharmacokinetics, a trend toward hematologic recovery, and improved survival outcomes in treated animals. For clinical chemistry and bone marrow histology, no significant changes were observed. CONCLUSIONS: These results indicate that IEPA has the potential to be further investigated as a MCM for ARS. To continue toward a clinical development path, the confirmation of the presented results with a study design adequately powered to assess a drug-mediated survival benefit is needed.
Wesołowski et al. (Tue,) studied this question.