Drug repurposing from the perspective of pharmaceutical companies

Abstract

Drug repurposing holds the potential to bring medications with known safety profiles to new patient populations. Numerous examples exist for the identification of new indications for existing molecules, most stemming from serendipitous findings or focused recent efforts specifically limited to the mode of action of a specific drug. In recent years, the need for new approaches to drug research and development, combined with the advent of big data repositories and associated analytical methods, has generated interest in developing systematic approaches to drug repurposing. A variety of innovative computational methods to enable systematic repurposing screens, experimental as well as through in silico approaches, have emerged. An efficient drug repurposing pipeline requires the combination of access to molecular data, appropriate analytical expertise to enable robust insights, expertise and experimental set-up for validation and clinical development know-how. In this review, we describe some of the main approaches to systematic repurposing and discuss the various players in this field and the need for strategic collaborations to increase the likelihood of success in bringing existing molecules to new indications, as well as the current advantages, considerations and challenges in repurposing as a drug development strategy pursued by pharmaceutical companies.

Antimicrobial and immunomodulatory activity induced by loperamide in mycobacterial infections

“…The development of novel pharmaceuticals can be deterred by the need to characterize drug pharmacokinetics, dosing, and safety information in humans [11]. Developing a new drug from a promising molecule with the aim of bring it to market can take ten years or more, and the cost is considerably high [20].…”

“…As loperamide can mediate intracellular calcium levels by blocking calcium channels and activating opioid receptors, several biological effects of loperamide have been described in addition to those involved in diarrhea control, suggesting its potential uses for alleviating pain, controlling anxiety, reducing insulin resistance and inhibiting coronavirus replication [4,[8][9][10]. The advantages of performing research dedicated to repurposing currently available drugs include a considerable reduction in the time and costs required to discover new therapeutic approaches [11].…”

A signalome screening approach in the autoinflammatory disease TNF receptor associated periodic syndrome (TRAPS) highlights the anti-inflammatory properties of drugs for repurposing

“…There would be advantages to patients and clinicians in developing drugs for TRAPS (and other autoinflammatory diseases) that are relatively cheap, taken orally, have a proven safety record and minimal side effects and target intra-cellular pro-inflammatory signalling pathways [27]. Identifying such drugs through a repurposing approach would offer major advantages in development costs and safety assessment [28][29][30].…”

Inventing new therapies without reinventing the wheel: the power of drug repurposing

“…According to some estimates, the cost is only $40-80 million in total for FDA approval through the repurposing route, compared to the $1-2 billion it takes to develop a drug starting from hit selection in vitro. However, this figure for repositioning may be too optimistic as it does not take into consideration the costs of failed repurposing trials (Bertolini et al, 2015;Ishida et al, 2016;Cha et al, 2018). In the often-quoted figure of $1-2 billion as the cost of new drug development (see Tufts Center for the Study of Drug Development; http://csdd.tufts.…”

“…This themed section on drug repurposing collates a number of reviews and original research papers on the topic. The authors of the reviews offer their unique perspectives derived from working in diverse environments: pharmaceutical companies with active repurposing programmes (Teva Pharmaceutical Industries) (Cha et al, 2018); governmental research institutions that specialize in this approach of drug development, such as the National Center for Advancing Translational Sciences (Zheng et al, 2018); and academic investigators who have a background of interest in certain pathways or mechanisms where repurposing opportunities present themselves (Berger et al, 2018;Korkmaz-Icöz et al, 2018a). In addition, the themed section compiles a number of original research papers, with new experimental data indicating the potential of repurposing the clinically used PARP inhibitor olaparib for non-oncological indications (Ahmad et al, 2018;Korkmaz-Icöz et al, 2018b); the long-acting PTH analogue LY627-2K (originally in development for osteoporosis) for the therapy of hypoparathyroidism-associated hypocalcaemia (Krishnan et al, 2018); the clinical-stage drug development candidate dexpramipexole for stroke (Muzzi et al, 2018); the 'age-old' antibiotic rifampicin as a neuroprotectant in traumatic brain injury (López-García et al, 2018); various clinical-stage glycogen phosphorylase inhibitors for type I diabetes (Nagy et al, 2018); the FDA-approved food additive β-caryophyllene for the therapy of alcoholic steatohepatitis (Varga et al, 2018); and various non-steroidal anti-inflammatory drugs (e.g.…”