Teaching old drugs new tricks: why companies reposition medicines

Repositioning a drug affords pharmaceutical companies the opportunity to enhance the return on their initial investment. bitzi/flickr

Many pharmaceutical companies are having to re-examine their product portfolio because of the difficult economic climate. New uses for established drugs affords a way for these companies to maximise financial return on their initial investment on various products.

Last year, it was reported that Ambien, a drug manufactured by Sanofi Aventis, was having some success in waking patients from long-term coma. These patients, many of whom were brain damaged, showed a positive response to the drug.

This novel use of the drug was all the more surprising since Ambien (also known as zolpidem) was developed for treating insomnia and is classified as a hypnotic or sleep-inducing compound.

Aspirin has been in use in some form or other for many hundreds of years. Archives of Bayer AG/Wikimedia Commons

Interestingly, the use of an established medicine for a newer therapeutic purpose is becoming increasingly common. Aspirin, a drug that’s been in use in some form or other for many hundreds of years was originally employed, and indeed still is, as a mild pain-relieving analgesic. But it’s probably more commonly used today as an antiplatelet agent helping to prevent blood clotting that can occur in thromboembolic disease.

Newer studies hint at a role for aspirin in the prevention of certain cancers; it’s a drug that seems to be continually reinventing its usefulness.

Some drugs have multiple uses because they have multiple modes of action. Amitriptyline (an antidepressant with a mild tranquillizing effect) has been used for over 50 years in the treatment of depressive illness. It exerts an antidepressive effect by blocking the reuptake mechanism of various neurotransmitters, the most important being serotonin and, to a lesser extent, noradrenaline. Elevated levels of these chemicals in the brain promote mood stabilisation.

But amitriptyline is also effective in the relief of neuropathic pain occurring as a result of nerve damage through injury or disease, a consequence of noradrenaline-elevating properties of the drug.

Why now?

To understand why drug repositioning (as using drugs for a new purpose is known) is attractive to pharmaceutical companies, it’s necessary to look at the process of how a drug enters the marketplace.

Drug discovery and development is a costly and time-consuming process. Each drug must undergo stringent preclinical and clinical tests to determine short- and long-term toxicology, patient tolerability of the compound and any adverse effects.

Viagra (sildenafil) was originally developed – and failed – as an anti-hypertensive agent. Felix E.Guerrero

All this happens before the effectiveness of the drug as a medicine can be determined. And failure in any of these tests will lead to that candidate compound being eliminated.

On average, from a starting library of 10,000 compounds, one drug is approved for medicinal use. The average cost of bring a new drug to the market is estimated to be upwards of US$1.7 billion, and the average time from discovery to approval is some 12 years.

This means there’s a limited exclusivity period for the drug company to recoup its investment in the drug. Once the patent has expired (usually 20 years from when the drug is registered), any company can manufacture and sell generic versions of the drug.

So, with this massive investment and a ticking clock, the repositioning of a particular drug affords big and small pharmaceutical companies alike an opportunity to enhance the return on their investment. In particular, savings in time and money can be made reinvestigating uses for compounds that have already been screened for safety and tolerability. Indeed, many companies now freely hand out such compounds to medical researchers with a view to repositioning if new uses are found.

Drug repositioning is generally a serendipitous event. bloodybee/flickr

But drug repositioning is, in general, a serendipitous event. Sometimes a drug developed for one purpose ends up being marketed for a completely different complaint. Although Viagra (sildenafil) was originally developed (and failed) as an anti-hypertensive agent, for instance, it’s currently marketed as a treatment for erectile dysfunction. In a second repositioning, sildenafil, this time branded as Revatio, is now used as a pulmonary antihypertensive.

Even drugs that have been previously withdrawn from use due to safety considerations can reappear when repositioned. Thalidomide, used in the early 1960s as a treatment for morning sickness, gained notoriety when severe birth defects appeared in over 10,000 children from mothers given the drug during pregnancy. This resulted in its withdrawal, but a repositioned thalidomide, with its teratogenic (tendency to interfere with normal embryonic development) adverse effects noted, is currently used in the treatment of leprosy and several types of cancer, including multiple myeloma (malignant bone marrow tumour).

Drug repositioning affords the opportunity to reinvestigate promising candidate medicines in a quicker, efficient and more economic manner. You can expect such drug realignments to become more commonplace in the future.

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