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European Biopharmaceutical Review

Fighting the Damocles Sword of Infectious Diseases Through Drug Repurposing

Today’s society faces a major challenge regarding the treatment of infectious diseases caused by viruses, bacteria, parasites, or fungi, which represent the second largest global mortality cause after cardiovascular diseases and the first in low income countries (1). Suboptimal vaccine efficiency (for those counted diseases for which effective vaccines are available), failure to develop a specific therapy, and/or the emergence of drugresistant pathogens that become able to survive currently used therapies account for this major public health burden. In that regard, global unprecedented and accelerated rates of antimicrobial resistance are being faced, spurred by an inadequate use of these drugs and key shortfalls in infection control measures. Antimicrobial resistance leads to 700,000 deaths worldwide, and the WHO forecasts 13 million deaths due to infectious diseases in 2050, estimating that 10 million deaths will be directly attributable to antimicrobial resistance (2).

A Steady Decline in De Novo Drug Discovery

Developing de novo classical drugs is very costly and time consuming, with approximately only 12% of drug candidates that make it into Phase 1 clinical trials receiving the final market authorisation by regulatory authorities. In other words, for each approved compound, roughly 5,000-10,000 candidates were left behind at different stages of the classic drug discovery pipeline (3). Despite constant efforts from both the industry and academia, as well as major technological improvements in the last 30 years or more, the capacity to discover and develop new antimicrobials is still being outpaced by the (re)emergence of microbes and the ability of current ones to become resistant to the few treatments available. This scenario does not seem to be changing for the better. Indeed, this steady decline in drug discovery productivity, despite constant increase in pharmaceutical R&D expenses, has been labelled under the ‘Eroom’s Law’, a backwards spelling of Moore’s Law, which describes the exponential advances in other technological fields (eg, electronics) over time (4). The causes are multiple, including tighter safety regulatory requirements for drug approval, a restrictive ‘single target-centred’ approach for compound screening, the targeting of more intricate diseases, the limitations of reductionist experimental models to reproduce biological complexity, or even the overestimation of some very early target-based experimental results and consecutive overinvestment of financial and human resources. Besides, the real consequence is that this situation is hindering the ability to prevent and respond to outbreaks which spread easily, favoured by the globalisation of trade and travel, for which alternative drug discovery strategies are underscored.

New Lives for Existing Drugs

According to the National Institutes of Health’s National Center for Advancing Translational Sciences, drug repurposing (also termed drug repositioning) is defined as the process of discovering new therapeutic uses for existing molecules (5). This process also comprises the evaluation and validation of the safety and efficacy for such second therapeutic indication. The apparently simple and generic concept of drug repurposing covers different approaches that can be independent or complementary to each other, such as:

• Finding a new clinical indication for a medicine or molecule, distinct for the initial intention that led (or not) to market approval
• The reformulation of the original molecule and/or the development of delivery mode alternatives to that of the first indication
• The combination of molecules to enable an additive or synergistic therapeutic effect on at least one of their respective indications

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Andrés Pizzorno holds a PhD in microbiologyimmunology from Laval University, Canada. With 10 years of research experience in the field of respiratory viruses, virus-host interactions, and antiviral strategies, he currently pursues his research activities at the VirPath Team of the Centre International de Recherche en Infectiologie in Lyon, France. Andrés is also co-founder and Project Manager of Signia Therapeutics, an innovative company based on a breakthrough proprietary drug discovery strategy to identify and repurpose already-marketed drugs rapidly, efficiently, and at low cost or to ‘rediscover’ unused drugs for new antimicrobial indications against several human pathogens.
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Andrés Pizzorno
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