Drug Repurposing: A New Life for Old Drugs

Drug repurposing is an approach that, while not new, has become popular in the last decade. Currently, about one-third of recent drug approvals and 25% of the pharmaceutical industry's annual revenue is coming from repurposed drugs.This trend is being championed industry-wide, by public organizations and nonprofits, with numerous small companies diving in and academic publications on the subject showing great popularity. 

One of the most exciting prospects of drug repurposing is its potential to tackle "undruggable" targets—proteins or molecules that traditional drugs can't easily bind to. The hope is that repurposing known drugs with already established safety profiles will help to overcome the challenges of undruggable targets. 

The benefits of drug repurposing are clear: development times and costs are significantly reduced due to existing knowledge about the drug's properties. Add to that, these drugs have already passed safety tests, meaning they could potentially move through early-phase trials faster if doses are compatible for new uses.

Historically, many successful repurposed drugs were discovered serendipitously, however, today's drug discovery community is increasingly adopting systematic, data-driven approaches, often with computational assistance. These include matching molecular signatures, virtual screening, and analyzing large datasets from health records and clinical trials. Drug repurposing’s potential to target undruggable molecules is showing huge promise for its ability to accelerate the development of new therapies and improve patient outcomes.

High-Potential Drug Candidates

Drugs that have successfully completed Phase III clinical trials are prime candidates for repurposing because their safety and efficacy in large populations have already been established. These candidates can be broadly classified into two categories: serendipitous discoveries and those identified through targeted research on a drug's MoA.

Generic drugs are also an interesting case and are common targets for repurposing due to their established safety profiles and long market presence. They also provide a level playing field for academics, biotech companies, and pharma giants to compete on. However, Pharma companies do have a some advantages when it comes to the proprietary data they have on failed or patented drugs, giving them a step ahead in exploring repurposing.

Another key element of repurposing is to understand the potential of existing drugs and the strength of the evidence you’re working with. This can be categorized using a framework known as the Drug Repositioning Evidence Level (DREL). This framework ranks evidence’s quality on a scale ranging from computational predictions to well-documented human studies. 

When it comes to practical repurposing strategies, it is essential to bridge the gap between experimental and computational approaches. Fortunately, advanced drug databases serve as powerful computational tools that can connect basic laboratory researchers with the vast array of in silico methods available for drug repurposing.

Challenges of Drug Repurposing

Drug repurposing shows a great deal of promise but it isn’t without its challenges. Legal aspects can complicate patenting new uses for existing drugs, reducing incentives for repurposing. Some countries restrict patenting second uses, and publicly available information can affect patentability. For off-patent drugs, new indication patents might be possible but hard to enforce. All of this amounts to a lot of barriers and high costs, making regulatory incentives and economic rewards that much more vital to ensuring repurposing is an attractive pursuit.

Research infrastructure also presents hurdles. Despite the rise of open-source models, access to valuable data, like clinical trials, remains limited. Additionally, integrating diverse data types is a high demand task, and obtaining generic active ingredients can be challenging, especially if the drug is no longer commercially available.

Opportunities in Drug Repurposing

There is great potential for drug repurposing to unlock treatments for rare and neglected diseases, where traditional drug development is too costly. Academic and non-profit organizations often lead these efforts, supported by regulatory measures and public policies that can include tax breaks, fast-track approvals, grants, and waived regulatory fees.

Personalized medicine or precision medicine is another emerging approach that is getting a great deal of attention. It takes into consideration individual variation in genes, environment, and lifestyle to create tailored treatments.Repurposing and precision medicine has already made  a significant impact in oncology, where genomic sequencing can identify potential drug targets, leading to repurposed treatments.

Network pharmacology, also known as systems medicine, integrates different drug discovery paradigms, offering a comprehensive view of drug actions. This approach is valuable for designing multi-target therapeutics or selecting synergistic drug combinations. For example, the combination of nifurtimox and eflornithine for Gambiense sleeping sickness is easier to administer and reduces treatment duration compared to monotherapy. Interestingly, both drugs in this combination are repurposed: eflornithine was initially developed for cancer treatment in the late 1970s, and nifurtimox was originally approved for American trypanosomiasis.

Repurposing drug combinations expands the possibilities beyond single-drug therapies. Combinations of drugs that work alongside one another can enhance drug efficacy and reduce required doses, increasing the success rate of repurposing.

We are also seeing exciting partnerships between pharmaceutical companies and academics, as they have shown their ability to complement each other in discovering new repurposing opportunities. Pharma companies are often rich with valuable chemical libraries and expertise, while academics bring emerging disease biology knowledge. These collaborations can drive innovation and help to develop industry wide expertise, further broadening our collective database of knowledge.

The Future of Drug Repurposing

Drug repurposing offers a powerful tool for accelerating drug discovery and development. The integration of electronic data capture, comprehensive databases, and advanced analytics provides a robust framework for evaluating repurposing candidates, which can significantly reduce development time and costs. Clinically, repurposing has the advantage of familiar drugs with known mechanisms and safety profiles. 

There are challenges with patent issues that may deter widespread adoption, but regulatory incentives could encourage repurposing research. By involving toxicologists and pharmaceutical scientists early in the process potential concerns can be addressed before they arise. 

Advancements in artificial intelligence (AI) and computational technology promise to alleviate current database challenges, streamlining data extraction, integration, and maintenance. The continued evolution of drug databases, computational chemistry, and AI integration offers exciting possibilities for the future, while rapid advancements in machine learning and deep learning are already transforming drug repurposing and other areas of healthcare research.

As traditional drug development faces challenges, drug repurposing presents an exciting opportunity to answer unmet medical needs.

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