I found this drug in the lab, shall we try it on our experiment? A lesson on drugs repurposing.

Lately, among the pharmacologists and life scientists, the concept of "drug repurposing" has increasingly become more common. As the expression suggests, drug repurposing consists of using an existing drug for a well-defined pathological condition, for a new treatment that was not indicated before. The condition for which the drug is repurposed can be even totally unrelated to the original disease for what the drug was developed and used. In this article, we are going to explore the importance of drug repurposing nowadays and some example of this new approach in pharmacology.

Why drug repurposing matters todays more than ever?

There are over 6,000 rare diseases, but less than 6% of them have approved treatments. Low presence of patients affected by these disease, the heterogeneity of patients' populations, the limited natural history of the diseases and their poor historical records, and high research and development costs represent among the factors limiting new therapeutic options for people with rare diseases. This is why drug repurposing might be a complementary approach in enhancing the drug discovery and development processes, especially in those cases where the achievement of an effective therapeutic system might be challenging. It can also offer various advantages over developing an entirely new drug for a given indication, such as fewer risks, lower costs, and shorter timelines.

What are the steps of drug repurposing? How does it work?

Drug repurposing involves identifying the drug, evaluating its efficiency using preclinical models, and proceeding to phase II clinical trials before this can be used as a new treatment. The identification of the drug can be carried out by using different approaches, either computational or experimental. The full drug repurposing process can last years, depending on how quick and easy the target drug identification is, but also on how successful experimental studies will be. A schematic of this process is reported in Figure 1. In the era of artificial intelligence algorithms and bioinformatics increasing popularity, the computational approach can represent a good first way to screen the information needed for the identification of a new therapeutic approach for an old drug. This involves the analysis of public databases for drugs, data from primary and translational research, clinical trials, anecdotal reports regarding off-label uses, and other published human data information available.

Figure 1: Stages of repurposing.

After the computational approach, a further validation step is needed, which involves a series of experiments with the aim of validating the hypothetical new use of the existing drug. This approach can include testing large drug libraries against disease-relevant targets or phenotypes in vitro, using cell-based or biochemical assays, or identifying genetic dependencies that can be targeted by known drugs. This can be the longest phase of the process (drug development phase in Figure 1, 1-6 years post-license acquisition for a drug). This is also the most risky step in the drug repurposing process, although the failure rates is still lower than the traditional drug discovery and development approach, due to a higher confidence in the starting product of the investigation.

Do we have yet repurposed drugs?

Yes, we do! Several examples of repurposed drugs are already reported in database and clinical use. Indeed, 94 cases are known in which a repositioned or repurposed drug made it to the market. A common example is the aspirin, initially developed and sold by Bayer in 1899 as an analgesic. This was repositioned in the 1980s, at low doses only, as an antiplatelet aggregation drug. Another example of repurposed drug is sildenafil, which was initially investigated by Pfizer in 1985 as a potential antihypertensive drug. However, an unexpected side effect emerged during clinical trials conducted in the United Kingdom, in the form of penile erections. This effect is the consequence of vasodilation promoted by the administration of sildenafil, and led Pfizer to market sildenafil in 1998 for erectile dysfunction, under the brand name Viagra. The last example of repositioned drug in this article, the dimethyl fumarate, was first synthesised in 1819. For almost two centuries, it was only known as a mould inhibitor and it was mostly used to protect leather. As a downside, it was found to be a cause of allergies, which led to a ban on its use in Europe in 2009. Even though side effects of this drug have been known for a long time, this drug has also been marketed since 1994 in Germany to treat psoriasis, under the brand name Fumaderm. These are just a few examples of repurposed drugs, althoug around 100 different drugs have already been repositioned from the original therapeutic area for which they were developed originally.

If repurposed drugs have all these pros, why are pharmaceutical companies not focussing yet mostly on repurposed drugs then?

Although from the previous paragraph it may sound like repurposed drugs represent the future of medicine and drug discovery, this idea is quite inaccurate and somewhat too optimistic. It is true that they allow a complementary tool for increasing the choices of therapeutic approaches to use against a pathological conditions. However, several downsides are easily identifiable for this class of drugs. Some of these reasons are the lack of efficacy or superiority to other therapies (the most common reason), strategic business reasons (quite common as well), safety problems (this happens often, as in many cases this was the reason why some drugs did not end for being marketed after clinical trials), the complex nature of a studied disease or drug and regulatory bodies requiring more information. Key barriers to repurposing usually include inadequate resources, and trial data access and transparency around abandoned compounds. Additional issues reside behind the uncertainty about the value of repurposing, liability risks, and intellectual property challenges.

Conclusion

Even though the issues described in the previous paragraphs of this article, the importance of these drugs is increasingly being recognized. This is why all the parties involved are trying to improve the collaborations to facilitate the repurposing processes. Multi-partner collaborations, along with the creation, accessibility, and use of compound databases, regulatory modifications and tax incentives are key facilitators for repurposing promising shelved drugs. Additionally, it is undeniable the importance of the constant need of more research to be done on the current value of repurposing as a core method in drug development, but also how to better facilitate resources to support it, where valuable.

References

Kulkarni, V. S., Alagarsamy, V., Solomon, V. R., Jose, P. A., & Murugesan, S. (2023). Drug Repurposing: An Effective Tool in Modern Drug Discovery. Russian journal of bioorganic chemistry, 49(2), 157–166. https://doi.org/10.1134/S1068162023020139

Zanello G, Ardigò D, Guillot F, Jonker AH, Iliach O, Nabarette H, O’Connor D, Hivert V. Sustainable approaches for drug repurposing in rare diseases: recommendations from the IRDiRC Task Force. Rare Dis Orphan Drugs J. 2023;2:9. http://dx.doi.org/10.20517/rdodj.2023.04

Bellino, S., Lucente, D., & La Salvia, A. (2025). Drug Repurposing of New Treatments for Neuroendocrine Tumors. Cancers, 17(15), 2488. https://doi.org/10.3390/cancers17152488

Jourdan, J. P., Bureau, R., Rochais, C., & Dallemagne, P. (2020). Drug repositioning: a brief overview. The Journal of pharmacy and pharmacology, 72(9), 1145–1151. https://doi.org/10.1111/jphp.13273

Krishnamurthy, N., Grimshaw, A.A., Axson, S.A. et al. Drug repurposing: a systematic review on root causes, barriers and facilitators. BMC Health Serv Res 22, 970 (2022). https://doi.org/10.1186/s12913-022-08272-z

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