Major pharmaceutical companies like AstraZeneca and GlaxoSmithKline (GSK) invested a staggering 140 billion US dollars between 1997 and 2011 in drug research and development. The cost to the consumer also varies widely, with the drug Copaxone (used to treat multiple sclerosis) costing nearly $4,000 a dose in the US, compared to just $862 in the UK. Even so called ‘affordable’ drugs, like Nexium (used to treat stomach acid) cost several hundred dollars per dose. Why are these drugs so expensive?
In part it is due to the competitive and profit driven nature of pharmaceuticals; but the major reason is that so many drugs fail during development. As a result, in order to continue researching and producing new drugs, pharmaceutical companies have to charge enormous amounts to recoup the amount of money lost on failed drugs. AstraZeneca, which spent nearly 60 billion dollars between 1997 and 2011, had only five drugs approved in that time. To put that in perspective, it cost them approximately 12 billion dollars to produce one usable drug! Clearly it’s in the best interest of both the consumer and the drug companies to see more drugs successfully make it to market. With that in mind, what are the major reasons why so many drugs fail, and can we do anything about it?
Image Credit: Public Domain Pictures
The drug discovery process is tightly regulated by different bodies depending on what country the company is operating in, but, as most major pharmaceutical companies are multinational, they effectively all follow a similar set of rules. Drug discovery begins by identifying a particular target – be it a protein to inactivate, a bacterium to kill, or a tumour marker to attack. From this, scientists can spend anywhere between three and 20 years working on new compounds. A lot of the time, they won’t even find anything useful!
Let’s assume that the company has found a useful compound it thinks could be a drug. The next step involves a series of trials. These begin with pre-clinical trials in non-human subjects such as mice and rats, and may progress onto dogs, cats, and primates. While controversial, drug companies are forced by law, to carry out animal testing – it’s not something they can just get away with ignoring. The Thalidomide tragedy, which resulted in severe birth defects in thousands of children, came about in part due to a lack of testing in model organisms.
Once the drug passes pre-clinical trials, and only about 10% make it this far, it then passes into three phases of clinical trials. This involves testing the drug on progressively larger groups of both healthy and affected patients to check safety, dosage, and side effects. Only when they are satisfied it’s an effective drug, can a pharmaceutical company apply for a licence to market their drug – and these are not cheap either! By the end of the process, a company may have spent billions investing in a potential drug, although only five per cent of them reach the end point.
Now that we know what’s happening, we have to ask why. Why do so many drugs fail clinical trials? There are a number of reasons. Firstly, model organisms such as rats and mice have different metabolic pathways to humans. This means that the way a drug interacts in one animal may be different from how it behaves in another. This doesn’t mean that animal testing is useless – it just means that more is needed to understand the differences.
Another major reason is that the theory behind a disease is wrong. At the beginning of the drug development process, we might understand very little about the disease. By the time the drug enters clinical trials (maybe 10-15 years later) we might have a much better understanding, only to realise that this means our original drug won’t work. Or we might not understand the disease at all (and this is surprisingly common). This is very true of Alzheimer’s, and is a major reason behind the lack of effective drugs. Whilst we might have a basic understanding of the factors at play, we still don’t know enough to make a drug that will actually work.
Side effects must also be considered. A drug might be very effective at treating an illness, only for it to have devastating side effects that make it a no-no for human use. For example, cancer researchers must try to limit the effects of chemotherapy agents (a tough job) in order to try and give the patient the best quality of life.
With all that in mind, you might be forgiven for thinking it’s a losing battle. Don’t despair. Our knowledge of disease is progressing at an ever increasing rate, and with it comes the hope of wonderful new ways of treating them. In the future, researchers hope to be able to better utilise specific cell cultures, taken from a patient, to better understand their unique disease profile and develop personalised medicines. Other technologies, such as gene editing, and nanotech, may also offer hope to millions of people suffering from disease.