Oxford Martin Schools: A Talk on the Future of Drug Discovery

In the penultimate of a series of seminars on ‘Tackling Challenges of the 21^st Century’, Chas Bountra, Professor of Translational Medicine in the Nuffield Department of Clinical Medicine, and Dr. Javier Lezaun, Deputy Director of the Institute for Science, Innovation and Society, discuss the current problems of the process of bringing a drug into market and the revolutionary new approaches they are taking.

The need for new drugs is ever present; the number of incidences of cardiovascular disease and cancer in people over the age of 65 is skyrocketing and recent epidemics over the past decade, most notably Ebola and other health conditions like diabetes, make the issue more pressing. Clearly, there is no time to be wasted in devising an effective drug for people who need it. Not that current drugs are very cost-effective. Professor Bountra gives the example of Vertex, a drug that costs $800 a day but only effectively works for around 4% of the people who take it.

It is not only the patients that need the drugs, but also the carers and relatives surrounding the patients. The cost of not having drugs is great in terms of time and resources required to provide continuing care for patients. We need to solve the root of the problem and actually heal people, not sustain them continuously with drugs and treatment. Professor Bountra provides an emotional anecdote that demonstrates the urgency of creating new drugs. A woman came up to him after an event and gave him details of her daughter’s brain, so that he can use it for testing on new drugs. This shows how desperate people are for new drugs.

So why are industries reluctant to put money and resources into the development of new drugs? From the industry’s perspective, there are three main challenges to overcome. Firstly, drug development is both expensive and unsustainable. The whole process from the conception of an idea for a new drug to actually getting the drug into market costs around $3.5 billion.

The second challenge is the difficulty of creating a drug that actually works. For example, there were 13 clinical trials for an Alzheimer’s drug that were all in phase 3 (involving human trials) – all failed. For the point of view of an investor who is putting a lot of money into these trials, these results can be very disheartening. However, if we don’t get a drug that works within the next few decades, Alzheimer’s, which is predicted to affect 1 in 85 individuals globally by 2050, will financially cripple society.

The last challenge is the most difficult to overcome most of all. It takes around 6-30 years to get a drug from conception, through all trials, into commercial market. To ensure safety, the drug must be tested in a multitude of different trials involving animals and humans, which is why the process takes so long.

So why do most clinical trials of new drugs fail? Professor Bountra identifies two main reasons: organisation and scientific. For organisation, most companies around the world are working on the same few molecules, proteins and targets from which to create new drugs from. The people from these companies read the same literature and go to the same conferences and so are using the same information to develop new drugs. When phase 2 of most clinical trials have a 90% failure rate, it is because everybody is using the same molecules that are bound for failure. These failed clinical trials are a waste of the patients participating in the trials, the money put into them and the careers of people working on the trials. This process of drug development is ethically and morally wrong, according to Professor Bountra. Nevertheless, he admits to doing the same thing while he was Vice President and Head of Biology at GlaxoSmithKline prior to coming to Oxford.

The second main reason for problems of drug discovery is scientific. There are still many diseases of which we don’t understand the causes of yet, most notably neurological disorders such as depression. For this kind of disease, there is no way of quantifying the level of disease (we can’t simply ask patients how depressed they are compared to yesterday, for instance). Even more so, we still don’t understand how some drugs work, most surprisingly paracetamol. You would think that for such a widely used over-the-counter drug, the mechanisms of how they work in the body would be understood. This is not the case. If we don’t even understand the common drugs used for everyday purposes, how can we design new ones for more serious conditions?

So what can we do? The first strategy that Professor Bountra and Dr. Lezaun propose is to pool resources from different companies and institutions. Each will contribute information and data that they have gained in a collective effort to find a new drug. This method prevents replication of results or testing on a molecule that doesn’t work. In this manner, Professor Bountra was able to recruit ten large pharmaceutical companies who each gave $8 million dollars over a period of four years to a project he is currently working on. This shows how the power of sharing can attract support and contribution from different organisations. The Wellcome Trust, for example, put £50 million into the research carried out by his laboratory and are planning on contributing another £9 million. This indeed is very comforting news, knowing that there is money going into efforts to discover new drugs.

The second important approach to take is to work only on new drug targets so that new antibodies or agents can be generated against diseases. Afterwards, these should be made freely available to any academic institutions or laboratories working on drug discovery. This removes the need for patents or the branding of intellectual properties. As a result of this transparency, an environment of trust is created that encourages other organisations to collaborate in the drug discovery effort (Professor Bountra’s research group now has more than 250 collaborations with other laboratories all over the world). This also makes the process of drug development much quicker and lowers the costs. The importance of open access information is an example of crowdsourcing science at its most effective.

In addition, every molecule discovered and every test carried out should be published into the media. This prevents duplication of tests on the same molecules over and over again, which is a waste of time. At the end of their talks, Professor Bountra and Dr. Javier mentions grim facts that further emphasise the urgency for new drugs to be developed. We are still giving out the same drug for Alzheimer’s that was distributed in 1914, for example. The lack of medicine for rare diseases is also worrying – big pharmaceutical companies will not be interested in developing a drug that is going to be used by only 60 people in the UK.

Professor Bountra and Dr. Javier leaves us with no doubt about the direction the future of drug discovery should take from now on: support industry and the sharing of information between different organisations to collectively create new drugs that are needed in the modern world.