It is almost received wisdom that significant sales opportunities will emerge for pharmaceutical manufacturers as the world’s population gets older, especially in rich world markets and ageing China. However, as drug companies attempt to capitalise on demand for treating diseases linked to old age, such as cancer and dementia, they face several significant challenges. Indeed, research on the relationship between intrinsic ageing and disease has been highlighted as a key priority.
That was the headline message for the global pharmaceutical industry in November at the second Astellas Innovation Debate, an annual event organised and funded by Astellas Pharma Europe. The conference explores the role of innovation in society, with this year’s debate entitled ‘The Age Crunch – Facts, Fears and the Future’, chaired by Lord Robert Winston, professor of science and society and emeritus professor of fertility studies at Imperial College London.
Held at the Royal Institution of Great Britain, in London, attending specialists discussed how the ageing population in both the UK and worldwide will affect health and social care and economics and society as whole, and explored the changes required in current attitudes as well as business and government strategies to overcome these challenges.
Clearly, the pharma sector will be at the sharp end of these developments – and they are already significant. According to the national population projections published by the UK Office for National Statistics in 2011, there are now more people aged 60 and above (10.3 million) in the UK than there are under 18, with the number of people aged 60 or over expected to pass the 20 million mark by 2031. And according to the United Nations Population Fund, one in nine of the world's population is now aged 60 or over, with that number projected to increase to one in five by 2050.
People are living long enough to get diseases that they would previously not have got
‘Ageing means that people are living long enough to get diseases that they would previously not have got,’ said Professor Tim Eisen, academic lead and Deputy Director of the cancer division at Addenbrooke's Hospital in Cambridge, UK. ‘More people are surviving to 70, 80, 90 and 100, and these are the ages where most solid malignancies will appear.’
Research published earlier this year by the UK charity Macmillan Cancer Support forecast that by 2020 almost one in two people in the UK will get cancer, although almost four in 10 of those will not die from it. Also, according to findings published in the Lancet Oncology in 2012, scientists at the International Agency for Research on Cancer (IARC) in Lyon, France, have predicted that the number of cancer cases across the world will rise from 12.7 million in 2008 to 22.2 million by 2030, an increase of around 75%.
Eisen said that the healthcare needs of the UK’s ageing population are being compounded by other challenges, such as rising obesity. ‘Cancer, particularly the most common cancers, are basically diseases of middle and older age – and that explains the majority of the increasing cancer incidence figures we are seeing. But it doesn’t explain the whole thing.
‘In some ways we’re ageing quicker – an orthopaedic surgeon will tell you that due to increasing obesity they are seeing knee and hip problems in people of an age in which they wouldn’t expect to see those sorts of problems, and similarly there will be a huge increase in some cancers linked to obesity, such as endometrial cancer. So it is not all a completely rosy picture that we’re ageing more slowly – in some ways we’re ageing more quickly.’
While it was recognised that the ageing population presents potentially huge new opportunities for the pharmaceutical industry, several speakers highlighted the extent of the challenges for medicine manufacturers in attempting to capitalise on the phenomenon of ageing.
Recent research that has revealed the limitations of manipulating the telomeres
Dr Elizabeth Blackburn, a Nobel laureate and the Morris Herzstein professor in biology and physiology at the department of biochemistry and biophysics at the University of California, outlined recent research that has revealed the limitations of manipulating the telomeres – the regions of DNA sequence repetitions located at the ends of chromosomes. The shortening of telomeres through ageing has been found to play a role in the development of certain age-associated diseases, such as macular degeneration, arteriosclerosis, osteoporosis, and other degenerative diseases that might be reversed by restoring telomere length.
Blackburn is the co-discoverer of telomerase – a ribonucleoprotein enzyme that adds DNA sequence repeats to the ends of DNA strands in the telomere regions, hindering the loss of important DNA from chromosome ends. Since its discovery in 1984, telomerase has been the subject of extensive clinical research.
However, she said that recent research has illustrated that while it has benefits, an increase in telomerase can also actually increase the risk of cancer. ‘What we understand from a lot of recent research in people is that when you have telomerase a little too active, which can happen even by just small gene changes, it increases the risks of cancers,’ she said.
‘So we are stuck between a rock and a hard place – if we don’t have enough maintenance of the telomere we get susceptibility to the degenerative diseases of ageing, including some kinds of cancers, but we don’t want to push the telomerase up, because very recent work is arguing strongly that too much is pushing the likelihood of cancer way, way into too high a risk category.’
Eisen stressed the importance of investing in new drugs for all conditions caused by ageing. ‘At the moment in oncology we are developing many, many new drugs specifically targeted to individual molecular characteristics of the tumour – this is an extremely expensive process. However, if you don’t invest in developing these new drugs it won’t happen. And if you doubt that, look at antibiotics – we haven’t historically invested in antibiotics, and we haven’t had a new class of antibiotics for more than a decade.’
Professor Thomas Kirkwood, the Associate Dean for ageing at the University of Newcastle’s Institute for Ageing and Health – the largest multi-disciplinary centre for biomedical research on ageing in Europe – said that to meet the needs of the ageing population, the relationship between intrinsic ageing and disease needs to become a much higher research priority.
We need to connect work on the fundamental mechanisms of ageing with work on the fundamental mechanisms of disease
In an interview with Manufacturing Chemist, he said: ‘There needs to be far more research that recognises that age itself is the single biggest risk factor for such a large slice of the medical conditions of importance today. We need to connect work on the fundamental mechanisms of ageing with work on the fundamental mechanisms of disease. We know that ageing is driven by different types of molecular and cellular damage, but as to the particular types of damage, this is still not understood, and we need vast effort to be directed towards it.’
He said that there needs to more use of integrative science, also called systems biology, which brings together, for instance, molecular cell biologists, chemists and computer scientists. ‘This can allow you to make sense of how all the different elements related to ageing and disease work together,’ he said.
Kirkwood explained that if investments in such research are made, the opportunities created by the ageing population for the pharmaceutical industry could be enormous. He said that a particularly promising area of research is that focused on replicative senescence, a state in which cells stop dividing but do not die. He explained that there are growing signs that a discovery related to replicative senescence made at Newcastle University three years ago could have huge significance for the drug industry.
‘With senescence people used to think there was no further division of the cell because it had run out of steam,’ he said. ‘But what we discovered is that there is an integrated damage-sensing mechanism within the cell that integrates the signals that come from all kinds of damage, and that this makes clear the pathways within which the cells potentially could become available as targets for drug interventions.’
He added: ‘The pharmaceutical industry is beginning to take notice of the real opportunities that might exist for drugs that can intervene in the mechanisms related to cellular senescence. Some pharmaceutical companies are now actively investing in research in this.’
The drug industry still hasn’t sufficiently got its head around the challenges that relate to ageing
However, he pointed out that the drug industry ‘still hasn’t sufficiently got its head around the challenges that relate to ageing’. He said that the challenges are not only related to fundamental questions, such as whether there are pharmacologically-sensitive targets that could be relevant to each of the different old-age diseases or to the intrinsic processes of ageing, but are also connected to the ways in which clinical trials are carried out, which he said are ‘almost not fit for purpose anymore’.
In particular, he said that multimorbidity must be accounted for to a much greater degree. The increasing challenges created by multimorbidity in the UK are highlighted by the prediction made by the UK’s select committee on public service and demographic change that there will be a 50% rise in the number of people with three or more long-term conditions in England by 2018 compared with 2008.
‘Conventional trials test a drug for efficacy against a particular disease, and they are testing people who are not very old and do not have a disease, so multimorbidity is not taken into account,’ said Kirkwood.
