How Did Drug Discovery Become So Slow?

Over the past 50 years or so, the technology used to discover new drugs has greatly improved. Computers have become orders of magnitude faster, our ability to synthesise new biologically active compounds has advanced, and genetic engineering has come of age. More recently, artificial intelligence is helping researchers to find new potential drug candidates. Yet despite all this, the cost of drug development has never been higher and the rate at which new medicines are reaching the market has plummeted.

This article by Alex Telford provides some interesting discussion on how this situation came about. It begins with the example of Paul Janssen, whose team developed over 70 new medicines between 1950 and 1970. Comparatively, a scientist working on drug discovery today might not even have worked on a single drug that makes it to market by the end of their career. Why? Are we running out of compounds to discover? Are greedy pharmaceutical companies or overbearing regulators to blame? This article argues that the truth is more nuanced, and is well worth a read. Here’s a summary of the key points:

• Drugs discovered during the ‘golden age’ of drug discovery were the first of their kind – there were no existing drugs for the condition they were treating at the time. Today most new drugs must ‘compete’ with drugs that are already in use and so the bar for success is higher.
• Clinical trials have become larger, because more statistical power is needed to prove that a new drug is better than an existing drug. This makes them more expensive and complicated to run. 
• Drug development is financially riskier. Where regulations once existed mainly to prevent fraud, various drug scandals led to a tightening of regulations over the years, with a particular emphasis on drug safety. Investigating and getting approval for a new drug is more expensive, usually takes a decade or longer, and the discovery of very rare side effects can scupper an otherwise effective drug late into its development after tens of millions have been spent. This makes drug development a riskier endeavour than it once was.

• Due to the aforementioned risk, companies choose to wait until one phase of drug development is complete before starting the next, even for things that could be done simultaneously. For example, companies could start scaling up production of a drug while clinical trials are still being done.
• Public attitudes to the pharmaceutical industry have changed. Due to the aforementioned scandals, people are generally more sceptical of pharmaceutical companies and so there is a demand for tighter regulations. While some level of scepticism is healthy and warranted, opposition to the accelerated development of Covid vaccinations is a good recent example of how too much scepticism can be detrimental to public health.

Would it be better if we could strip away all the regulations and bureaucracy and go back to the 1950s? Probably not – even though we were getting more new drugs back then, ethical and safety standards were well below what most people today would consider acceptable. This article is not suggesting that we go back to those times, but does argue that the pendulum may have swung too far the other way, leading to a level of inefficiency that does more harm than good. One cited example of inefficiency is the existence of outsourced contract research organisations (CROs), trusted groups that conduct trials on behalf of pharmaceutical companies and pocket the change – a necessity that did not exist when trials were cheaper and simpler to conduct. 

It’s not all doom and gloom, though. If you look back at that first graph, you can see that there has been a small uptick in the efficiency of drug development over the last decade. Two possibilities are presented for why this might be the case. The pessimistic view is that companies are increasingly chasing drugs for rare untreatable diseases, since it’s easier to demonstrate that benefits outweigh risks when you’re targeting a disease with no existing treatment. The more optimistic view is that the benefits of all the new technologies we have gained (especially gene and cell-based technology) are finally catching up with the negative effects of regulation and opening up new classes of treatment. 

The development of Covid vaccines is proof that new treatments can be developed, trialled and manufactured at a greatly accelerated pace without compromising safety. While genetic sequencing and engineering certainly accelerated the development process, the author points out that this was still only possible because companies were protected from financial risk by government funding. Had Covid-19 not been a global health emergency, it may still have taken many more years to conduct clinical trials before slowly ramping up production.

So, how do we improve the current situation without compromising on the safety of new drugs? Three main solutions are proposed:

• Improve the quality of the molecules that are tested in clinical trials in order to boost their success rate. Things like better disease models that more accurately reflect human diseases can give us a better idea about whether a drug will actually work in humans, cutting down on time and effort wasted pursuing drugs that only work in mice.
• Make drug development easier/cheaper. One proposition to achieve this is to scale the required standard of evidence in accordance with the need for new treatments. For example, drugs targeting lethal diseases with few existing treatments could have less demanding thresholds for statistical significance, while post-marketing surveillance could be increased.
• Incentivise long-term investments in new technologies, so that those technologies have a better chance of reaching the maturity needed to actually see the light of day.

When it comes to efforts to delay the ageing process, regulations on drug development have most definitely failed us. Since ageing is not considered a disease by regulators, there’s no way to test or seek approval for a treatment aimed at slowing ageing in humans. Ageing is a condition with an incidence of 100% and that is also 100% lethal and currently incurable, so given the arguments above, regulations around such treatments should surely be relaxed.