UCL Emeritus Professor of Pharmaceutical and Public Health Policy
Fibrotic diseases, which involve the harmful deposition of excessive amounts of connective tissue within organs such as the lungs or the heart, can be seen as a perversion of healthy scarring. The difference is that while the latter repairs the body after damage has taken place conditions like, for instance, cystic fibrosis, Crohn’s disease and liver cirrhosis have destructive effects that can ultimately kill. The various mechanisms involved are not as yet fully understood but are linked to abnormal inflammatory, immune and allied responses to external challenges, coupled with genetic vulnerabilities.
Pulmonary fibrosis (PF, or ‘lung scarring’) is a relative rare fibrotic illness. It is frequently of unknown origin, albeit that some cases are linked to factors like, for instance, the use of medicines such as methotrexate and certain antibiotics, or the occurrence of ‘background’ diseases like heart failure or chronic bronchitis. As it develops PF causes constant coughing and increasingly severe breathing problems. Ultimately – typically after considerable physical and mental distress – it results in death.
Commonly quoted figures on its incidence could well be under-estimates, in that milder PF cases may pass undiagnosed. This might in part be because of the limited treatment available. Until today the main therapeutic choice has – short of lung transplants – been to provide interventions such as giving oxygen and anti-inflammatory and immuno-suppressant medicines. Doctors have had little reason to find early cases, and may have feared counter-productively labelling those they suspected of beginning to develop PF.
However, it appears that the incidence of PF in countries such as the US and those of Western Europe is currently approaching 10 per 100,000 population, and that the prevalence is 30-40 per 100,000. This implies an average survival time from diagnosis of around three years, less than that for many cancers.
Pulmonary fibrosis is an example of a rare disease as defined in the US Orphan Drugs Act and similar legislation across the world, albeit that at the global level there are in total over 2 million people living with it at any one time. The goal of orphan drug legislation is to incentivise private (and linked public) investment into rarer disease research and treatment development. Yet low volume sale, high science based, therapies are inevitably relatively expensive when they are first marketed. Many health care funders/providers tend to be unwilling to pay the prices asked for by innovators during the ten to fifteen year periods in which intellectual property rights apply.
In the last year two new medicines, nintedanib and pirfenidone, have become available for the treatment of idiopathic (unknown origin) pulmonary fibrosis. Their full potential is as yet unknown. But there is evidence that both drugs (which have differing modes of action) can slow the progression of the disease and may in time, notwithstanding side-effect risks, prove to be of value in other contexts. These include not only – perhaps – early stage or ‘pre’ PF treatment but also modifying other fibrotic disease processes.
Critics of what are at the time of launch highly priced and potentially health service cost increasing pharmaceutical innovations may argue that drugs such as nintedinab are not worth the money currently being asked for them. This may be because the projected ‘cost per incremental QALY’ is above the level assumed to be affordable. Less overtly, it may also be because of fears that they will extend the survival of seriously disabled individuals and hence prove costly in overall care provision terms.
Such negative judgements threaten to undermine the moral purpose of orphan drug legislation. They may also be ill-founded in that despite all the drug advances made since the 1940s pharmaceutical costs have in recent decades stayed reasonably constant as a proportion of health spending. As new medicines are introduced older ones become low cost generics.
Narrow Health Technology Assessments (HTA) fail to reflect the long term value of bio-scientific innovations which over time will lead to fully effective, low cost, treatments for savage diseases like pulmonary fibrosis. Despite the ‘austerity’ pressures on health care funders and the current unpopularity of pharmaceutical companies that are seeking premium returns for what may seem to be treatments of merely marginal additional value, the marketing of products such as pirfenidone and nintedanib for me represent profoundly important stepping stones to a better world.
Health care organisations have to work within their budgets. This means making hard choices. But at the same time reductionist HTA calculations are too simplistic to reveal the true worth of advances which are individually limited but nevertheless important parts of humanity’s continuing progress towards understanding biology in its entirety. In the long term biomedical progress is leading not only to technologies for preventing or curing ill-health but to wider gains that will contribute to both individual and collective survival and well-being in the coming century.
My fear is that desires for short term savings and the political pursuit of the immediate approval of the greatest number of voters will pervert public priorities, and in the coming decade drown this message out in settings like Europe. This could lead to much needless suffering. But my hope is that people and organisations of good-will, from patient and carer groups to health professionals, will be able to understand the important opportunities becoming available, and be successful in communicating the case for continuing to invest in developing and using better treatments for conditions such as pulmonary fibrosis.