**2. Traditional drug discovery vs. drug repurposing**

The traditional approach to drug discovery involves *de novo* identification and of new molecular entities (NME), which include five stages: discovery and preclinical, safety review, clinical research, FDA review, and FDA post-market safety monitoring. It is a time-consuming and costly process with high risk of failure [8]. On the other hand, there are only four stages in drug repositioning, which include compound identification, compound acquisition, development, and FDA post-market safety monitoring [9] (**Figure 1**). With the advancement of bioinformatics/cheminformatics tools and availability of huge biological and structural database, drug repositioning has significantly decreased the time and cost of the drug development with reduction in risk of failure. In recent years, the use of *in silico* techniques along with the application of structure-based drug design (SBDD) and artificial intelligence (AI) technology has further accelerated the drug purposing process [10, 11].

However, the repositioning strategy of using approved therapeutics for new therapeutic indications has demonstrated success particularly through prior serendipitous observations. The discovery of drugs by this approach is certainly advantageous as depicted above over traditional drug discovery program as described below. For example, sildenafil (Viagra), a phosphodiesterase-5 (PDE5) inhibitor initially developed for coronary artery disease (angina) by Pfizer (1985) has been repurposed for the treatment of erectile dysfunction. It potentially reduced the development cost at shorter development time. Metformin (Glucophage), an oral anti-diabetic medication used widely in type 2 diabetes mellitus has been developed as a cancer therapeutic which is currently under phase II/phase III clinical trials [1, 12].

Drug repositioning has several advantages in comparison with traditional approaches to drug discovery. When comparing with traditional drug discovery program, a significant reduction of the time spent in R&D can be observed. In traditional approach, it is estimated that 10–16 years are spent for the development of a new drug, while in DR the estimated time is between 3 and 12 years. It only costs \$1.6 billion to develop a new drug using a drug repositioning strategy, while the drug development through traditional strategy costs around \$12 billion. Moreover, researchers only need 1–2 years to identify new drug targets and about an average of 8 years to develop a repositioned drug [6, 7]. A repositioned drug does not require the initial 6–9 years typically required for the development of new drugs

**5**

**Figure 1.**

*Traditional drug discovery vs. drug repurposing.*

*Drug Repurposing (DR): An Emerging Approach in Drug Discovery*

by traditional process, but instead enters directly to preclinical testing and clinical trials, thus reducing the overall risk, time and cost of development. Reports suggest that repurposed drugs require approximately 3–12 years for gaining approval from FDA and/or European Medicines Agency (EMA) and at reduced 50–60% cost. At the beginning of a repositioning project, a range of pre-clinical (pharmacological, toxicological, etc.), and clinical efficacy and safety information is already available, as the candidate drug has already undergone through the early stages of drug development such as structural optimization, preclinical and/or clinical trials, in addition to the possibility of the candidate drug being an approved drug, having its clinical efficacy and safety profile. In this way, there is a reduction of the risks associated with failures in the early stages of development, which are high in traditional approaches, as well as a significant reduction of cost with the possible increase in

Due to the availability of previously collected pharmacokinetic, toxicological, clinical and safety data at the start of a repurposing development project, the advantages that are encountered with drug repurposing over traditional drug discovery approach are reduced time of development, lower cost of development

It has been estimated that the time required for development of a repositioned drug varies from 3 to 12 years (which is about 10–17 years in traditional discovery program) with substantially lower costs, which ensures the repositioning company's significant savings in terms of time and capital. The average cost required to bring

clinical safety and therefore, high success rate [13, 14].

and reduced risks of failure in the clinical development.

*DOI: http://dx.doi.org/10.5772/intechopen.93193*

*Drug Repurposing - Hypothesis, Molecular Aspects and Therapeutic Applications*

used to treat erectile dysfunction.

**2. Traditional drug discovery vs. drug repurposing**

failure rate of ~45% is associated due to safety or toxicity issues in traditional drug discovery program with additional benefit of saving up to 5–7 years in average drug development time [4, 5]. In recent years, the drug repositioning strategy has gained considerable momentum with about one-third of the new drug approvals correspond to repurposed drugs which currently generate around 25% of the annual revenue for the pharmaceutical industry [6]. It has been accounted that approximately 30% of the US Food and Drug Administration (FDA) approved drugs and biologics (vaccines) are repositioned drugs. According to recent estimates, pharmaceutical industries have significantly placed the market for repurposed drugs at \$24.4 billion in 2015 with projected growth up to \$31.3 billion in 2020. The first example of drug repositioning was an accidental discovery/serendipitous observations in the 1920s. After about a century of development, more approaches were developed for accelerating the process of drug repositioning. Some most successful and best-known drugs that have been emerged out of the DR approach are sildenafil, minoxidil, aspirin, valproic acid, methotrexate etc. [7]. For example, sildenafil originally developed for the treatment of hypertension and angina pectoris has currently been

The traditional approach to drug discovery involves *de novo* identification and of new molecular entities (NME), which include five stages: discovery and preclinical, safety review, clinical research, FDA review, and FDA post-market safety monitoring. It is a time-consuming and costly process with high risk of failure [8]. On the other hand, there are only four stages in drug repositioning, which include compound identification, compound acquisition, development, and FDA post-market safety monitoring [9] (**Figure 1**). With the advancement of bioinformatics/cheminformatics tools and availability of huge biological and structural database, drug repositioning has significantly decreased the time and cost of the drug development with reduction in risk of failure. In recent years, the use of *in silico* techniques along with the application of structure-based drug design (SBDD) and artificial intelligence (AI) technology has further accelerated the drug purposing process [10, 11]. However, the repositioning strategy of using approved therapeutics for new therapeutic indications has demonstrated success particularly through prior serendipitous observations. The discovery of drugs by this approach is certainly advantageous as depicted above over traditional drug discovery program as described below. For example, sildenafil (Viagra), a phosphodiesterase-5 (PDE5) inhibitor initially developed for coronary artery disease (angina) by Pfizer (1985) has been repurposed for the treatment of erectile dysfunction. It potentially reduced the development cost at shorter development time. Metformin (Glucophage), an oral anti-diabetic medication used widely in type 2 diabetes mellitus has been developed as a cancer therapeutic which is currently under phase II/phase III clinical trials [1, 12]. Drug repositioning has several advantages in comparison with traditional approaches to drug discovery. When comparing with traditional drug discovery program, a significant reduction of the time spent in R&D can be observed. In traditional approach, it is estimated that 10–16 years are spent for the development of a new drug, while in DR the estimated time is between 3 and 12 years. It only costs \$1.6 billion to develop a new drug using a drug repositioning strategy, while the drug development through traditional strategy costs around \$12 billion. Moreover, researchers only need 1–2 years to identify new drug targets and about an average of 8 years to develop a repositioned drug [6, 7]. A repositioned drug does not require the initial 6–9 years typically required for the development of new drugs

**4**

**Figure 1.** *Traditional drug discovery vs. drug repurposing.*

by traditional process, but instead enters directly to preclinical testing and clinical trials, thus reducing the overall risk, time and cost of development. Reports suggest that repurposed drugs require approximately 3–12 years for gaining approval from FDA and/or European Medicines Agency (EMA) and at reduced 50–60% cost. At the beginning of a repositioning project, a range of pre-clinical (pharmacological, toxicological, etc.), and clinical efficacy and safety information is already available, as the candidate drug has already undergone through the early stages of drug development such as structural optimization, preclinical and/or clinical trials, in addition to the possibility of the candidate drug being an approved drug, having its clinical efficacy and safety profile. In this way, there is a reduction of the risks associated with failures in the early stages of development, which are high in traditional approaches, as well as a significant reduction of cost with the possible increase in clinical safety and therefore, high success rate [13, 14].

Due to the availability of previously collected pharmacokinetic, toxicological, clinical and safety data at the start of a repurposing development project, the advantages that are encountered with drug repurposing over traditional drug discovery approach are reduced time of development, lower cost of development and reduced risks of failure in the clinical development.

It has been estimated that the time required for development of a repositioned drug varies from 3 to 12 years (which is about 10–17 years in traditional discovery program) with substantially lower costs, which ensures the repositioning company's significant savings in terms of time and capital. The average cost required to bring

a new drug to market is USD 1.24 billion by traditional drug development process, whereas in drug repurposing it costs around ≤60% expenditure of traditional drug discovery. Some other advantages are as follow. The primary focus of traditional discovery program is to discover drugs to treat chronic and complex diseases, whereas by drug repositioning approach, development of drugs for rapidly emerging and re-emerging infectious diseases, difficult to treat diseases and neglected diseases (NTDs) are focused. Due to the availability of bioinformatics or cheminformatics approaches, huge omics (proteomics, transcriptomics, metabolomics, genomics etc.) data and database resources, disease targeted-based repositioning methods can be used to explore the unknown mechanisms of action (such as unknown targets for drugs, unknown drug–drug similarities, new biomarkers for diseases etc.) of known/existing drugs [13].
