What’s the use of drug repurposing?

What’s happening? Drugs commonly used to treat hypertension and inflammation may also be beneficial for Alzheimer’s, a paper in Genome Medicine suggests. Researchers first characterised the initial, intermediate and advanced stages of the disease in mice studies. They then used a computational tool to screen for approved drugs that may reverse the effects at a cellular level. The team tested the resulting candidates in various Alzheimer’s mouse models. It was discovered that dexketoprofen and etodolac – both non-steroidal anti-inflammatory drugs – and the anti-hypertensives penbutolol and bendroflumethiazide were effective at reversing Alzheimer’s and reducing its symptoms. (IRB BarcelonaGenome Medicine) 

Why does this matter? Drug repurposing garnered much attention over the Covid-19 pandemic as scientists scrambled to find effective treatments for the infection. Although the idea is far from new, it is gaining momentum for diseases without effective treatments.  

Out of thousands, Alzheimer’s is just one example that could benefit from a repurposed drug and it’s an area that’s gained a lot of attention. In addition to the above, other recently identified and already approved drugs with the potential to treat the neurological condition include the diuretic bumetanide, constipation medication prucalopride and chemotherapy drug axitinib (Pfizer’s Inlyta). A combination of cholesterol-lowering drug gemofibrosil and vitamin A derivative retinoic acid has also been flagged as a possible therapeutic.  

Developing a drug from scratch and getting it to market typically takes around 10-12 years and can cost up to $2bn to cover all stages of research and development. It’s also a risky business given there’s no guarantee a drug will receive regulatory approval and many fail during development.  

Approved drugs already have established safety and efficacy data, meaning that researchers seeking to repurpose them for new indications can skip the earlier developmental stages and hit the human trial stage quicker. This can result in faster regulatory approvals, meaning patients with high or unmet medical needs receive more timely treatments. Identifying potential candidates for repurposing is also becoming more efficient due to advancements AI and machine learning technologies. Ultimately this drastically cuts developmental costs and the price of the resulting product.  

What’s the problem? Although this all sounds very promising, many repurposing candidates have gone off-patent or are generic, meaning pharmaceutical companies have low interest in investing in them for new indications as they will see little return. Instead, it’s academia, research institutes and collaborative efforts that lead the way in studies of drug repurposing. Getting their discoveries into confirmatory Phase III trials, however, is an expensive process that requires additional financial support 

How can it be fixed? Funding traditionally comes from sources such as philanthropic organisations, charities, governments and companies, but these pots are becoming increasingly smaller. Newer alternatives can come from social impact bondscrowdfunding or public-private partnerships. These, however, can be challenging for researchers to navigate due to reasons like lack of expertise or difficulty in measuring health outcomes. 

Perhaps another potential alternative lies in subscription models, which the UK’s National Health Service is utilising for antibiotics, whereby pharmaceutical companies are paid upfront for their products based on their usefulness for patients as opposed to price per pack. While this is designed to tackle the growing threat of antimicrobial resistance, it’s not unreasonable that such an incentive could be applied to drug repurposing too as a way of getting new treatments to patients in greatest need.  

Oops – Sometimes drug repurposing can be the result of an accident. One the most famous examples is Viagra (sildenafil). Pfizer was developing the drug for cardiovascular issues, but an outstanding side effect noted in clinical trials led to a repositioning, which changed the lives of millions of men suffering erectile dysfunction across the globe and a blockbuster drug for the company.  

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