Repurposing Pharmaceuticals Previously Approved by Regulatory Agencies to Medically Counter Injuries Arising Either Early or Late Following Radiation Exposure.

Vijay K Singh,Thomas M Seed

doi:10.3389/fphar.2021.624844

Abstract

The increasing risks of radiological or nuclear attacks or associated accidents have served to renew interest in developing radiation medical countermeasures. The development of prospective countermeasures and the subsequent gain of Food and Drug Administration (FDA) approval are invariably time consuming and expensive processes, especially in terms of generating essential human data. Due to the limited resources for drug development and the need for expedited drug approval, drug developers have turned, in part, to the strategy of repurposing agents for which safety and clinical data are already available. Approval of drugs that are already in clinical use for one indication and are being repurposed for another indication is inherently faster and more cost effective than for new agents that lack regulatory approval of any sort. There are four known growth factors which have been repurposed in the recent past as radiomitigators following the FDA Animal Rule: Neupogen, Neulasta, Leukine, and Nplate. These four drugs were in clinic for several decades for other indications and were repurposed. A large number of additional agents approved by various regulatory authorities for given indications are currently under investigation for dual use for acute radiation syndrome or for delayed pathological effects of acute radiation exposure. The process of drug repurposing, however, is not without its own set of challenges and limitations.

Highlights

Exposure to intense ionizing radiation will evoke invariably significant damage to selective tissues of vital organ systems of the body; most notably, the vascular, blood-forming, gastrointestinal, and reproductive systems
Despite substantial efforts over the last several decades to advance effective and safe radiation medical countermeasures for acute radiation syndrome (ARS) and for DEARE, a limited number of countermeasures have been fully approved by the Food and Drug Administration (FDA) for clinical use for humans (Singh et al, 2017a; Singh et al, 2017b; Singh and Seed, 2017; Singh and Seed, 2020b)
A current, prime example of the latter ‘repurposing process’ involves the antiviral agent, remdesivir (Gilead Sciences, Inc., Foster City, CA) and its use in treating severely ill COVID-19 infected patients (Gilead Sciences Inc., 2020). This agent was originally part of a bank of antivirals set aside by Gilead that was deemed in initial clinical testing to be ineffective in managing SARS-like infections, but was later rescued, clinically retested, and subsequently brought through the FDA’s regulatory approval process in record time in order to pursue it as an effective remedy for the current raging COVID-19 (Coronavirus disease 2019) pandemic (US Food and Drug Administration, 2020b)

Summary

INTRODUCTION

Exposure to intense ionizing radiation will evoke invariably significant damage to selective tissues of vital organ systems of the body; most notably, the vascular, blood-forming, gastrointestinal, and reproductive systems. A current, prime example of the latter ‘repurposing process’ involves the antiviral agent, remdesivir (Gilead Sciences, Inc., Foster City, CA) and its use in treating severely ill COVID-19 infected patients (Gilead Sciences Inc., 2020) This agent was originally part of a bank of antivirals set aside by Gilead that was deemed in initial clinical testing to be ineffective in managing SARS (severe acute respiratory syndrome)-like infections, but was later rescued, clinically retested, and subsequently brought through the FDA’s regulatory approval process in record time in order to pursue it as an effective remedy for the current raging COVID-19 (Coronavirus disease 2019) pandemic (US Food and Drug Administration, 2020b). Conventional drug development has a roughly 90% attrition rate; this is to say that 90% of the candidate drugs studied in TABLE 1 | US FDA-approved growth factors for other indications repurposed for H-ARS as radiomitigators

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Findings

DISCUSSION