Rare diseases and rarer treatments

R&D into new pharmaceuticals has improved quality of life and boosted life expectancy significantly since the very first physician told a patient to take two aspirin. Despite the doom-mongering about antibiotic resistant superbugs and the emergence of new diseases, such swine flu, vaccinations, antibiotics and antiviral drugs have been very successful. Moreover, important advances have been made in cancer treatment and in lowering death rates from cardiovascular disease. There have even been significant improvements in treating the seemingly modern diseases of the aging population, including Alzheimer’s and Parkinson’s, although “cures” for these and others remain elusive.

However, with the era of the blockbuster pharmaceutical product apparently long gone, drug patents expiring daily, and the drying up of research pipelines, the industry is gradually turning its attention to previously ignored diseases. If a company can no longer service its shareholders with blockbuster profits from a single drug, then how about a dozen products performing at a tenth that level, instead? Indeed, regulatory and legislative pressure in the US and the EU is forcing the industry to take a look at many well-known and widespread diseases for which there are no treatments.

The US Rare Disease Act of 2002 defined rare diseases based on prevalence. Any condition afflicting fewer than 200,000 people in the US (about 1 in 1,500) was given this status; not much of a change from the definition in the Orphan Drug Act of 1983 that was supposed to encourage research into rare diseases and possible cures. The Japanese defined an orphan disease as one Japan, affecting fewer than 50,000 people in Japan (1 in 2,500). Europe, on the other hand, defined these diseases based, not on prevalence, but on their life-threatening or chronically debilitating nature and how much special combined effort would be needed to tackle them. By virtue of this definition, threshold of prevalence for the majority of those conditions was 1 in 2,000; half way between the definitions used in the US and Japan.

However you define them and whether you distinguish between simply rare and orphan diseases, there are plenty to choose from anyone of which might open up new markets for an industry that has repeatedly been caught on the back foot recently, not least because of economic downturns. Orphanet, which as the name might suggest is a portal for information on rare diseases and orphan drugs, suggests that “There is no disease so rare that it does not deserve attention.” Moreover, just because a disease is rare does not mean that many people are affected.

Look again at those numbers above – by definition 200k might be afflicted with a given “rare” disease in the US alone. There are rare diseases that affect only a handful of people, but even assuming a generous average of say, 10,000 patients per disease, that’s well over 100 million people around the world suffering from one of the mere 10,000 or so rare diseases listed by Orphanet. At the upper extreme, we might assume that adding up incidence across each continent might mean a million people or so with each one. In other words, it is plausible that well over a billion people have a rare disease.

I asked Orphanet’s Segolene Ayme to validate my Fermi calculation. “The true prevalence of rare diseases is unknown,” she told me, “there is no source of data at population level.” She points out that prevalence data quoted in articles and policy documents have no documented sources and the published data by listed by disease in the Orphanet Report series “Prevalence of RD” is somewhat skewed towards very low numbers. “Of the 6,000 RD listed in Orphanet, only 105 have a prevalence ranging from 5 to 1 in 10,000 and 233 RD have a prevalence ranging between 1 in 10,000 and 1 in 100,000,” she told me. “Another 1,000 RD have probably a prevalence of around 1 per million, all the other ones affecting only a few patients worldwide, usually due to a single mutation segregating in family members.”

Among that growing list are Gaucher’s disease, tyrosinemia type 1, Aarskog syndrome, dancing Eye syndrome, Kahler’s disease, Q fever, Takayasu arteritis, Waardenburg anophthalmia syndrome and Zygomycosis…there are thousands of others known and probably thousands more that remain unidentified.

Andreas Zaby of the Berlin School of Economics and Law, in Germany, has analysed the impact of legislation, specifically in the EU on stimulating R&D into orphan diseases. He has found that the legislative incentives for developing orphan drugs does indeed hold some potential, though much remains to be improved. As such, he makes several suggestions regarding future efforts. “The development of orphan drugs alone is not sufficient for an adequate treatment of patients suffering from rare diseases,” Zaby says. “Due to the lack of information on these diseases, the creation of expert networks, specialised care facilities and reference centres for research and treatment are necessary.” He points out that future funding of public–private partnerships in basic research is needed to help science gain a better understanding of the countless rare conditions from which we suffer. Finally, he advocates, as have others, an internationally harmonised approach to orphan diseases, perhaps in close collaboration with the World Health Organization.

Research Blogging IconAndreas Zaby (2011). Orphan drugs: ten years of experience with the EU framework on stimulating innovation for treating rare diseases Int. J. Technology, Policy and Management, 11 (3/4), 291-306


Author: 雷竞技官网

Award-winning freelance science writer, author of Deceived Wisdom. Sharp-shooting photographer and wannabe rockstar.