In 1983, the population of the United States was approximately 233 million people. More than 30 years later, the US population is now closer to 313 million-an increase of 82 million people. But while the increase has been good for many things, it has been perversely disadvantageous for patients with rare diseases.
In 1983, Congress passed the Orphan Drug Act, a piece of legislation meant to provide incentives for manufacturers to develop therapies to meet the needs of patients suffering from rare and orphan diseases.
The problem legislators intended to solve was this: Because "rare diseases" are (by definition) uncommon, pharmaceutical companies typically decided that the market size for the drugs was too small to make it worth their while to invest in new therapies. As a result, many diseases lacked any proven therapies,
The Orphan Drug Act remedied this by permitting FDA to give the products approved to treat the orphan conditions special marketing protections (7 years of market exclusivity), tax credits to offset some of the costs of development, faster regulatory reviews and additional assistance from FDA reviewers during the development and review process.
Crucially, it also defined the term "rare disease or condition" as one affecting fewer than 200,000 persons in the US.
A Population Problem
The use of a static number-200,000-is important. In contrast, the EU, which has similar orphan drug provisions, uses a proportion of the population to define rare disease-no more than five in 10,000 people in the EU.
And therein lies the problem for patients with rare diseases living in the US: As time goes on, the standard for rarity is slowly becoming more restrictive.
So in 1983, when the US population was 233 million people, a rare disease could be present in no more than 0.085% of the population.
By 2014, that proportion had shrunk to 0.064-a decrease of 24.7% in the definition of "rare" in 30 years.
Still, US patients are still in better shape than those in the EU, where the 5-in-10,000 ratio works out to a constant 0.05% of the population. But that advantage will cease to exist once the US population hits 400 million, which it is expected to do in 2050, according to US Census estimates.
What to Do?
It's not clear how many-if any-rare diseases have been affected by the reduction in proportion since 1983. The National Organization for Rare Diseases (NORD) lists more than 1,200 diseases on its website, and notes that approximately 7,000 are thought to exist in the US alone. The National Institutes of Health (NIH) also maintains an extensive list of rare diseases, but neither NIH's nor NORD's list contains estimates of how many patients are thought to be affected by each condition.
However, if a disease is thought to affect 199,999 patients in 2014, any new additions through population growth would cause it to no longer be "rare" under the Orphan Drug Act, making it ineligible for any of FDA's special incentives. While that would be unlikely to change anything for already-approved drugs or therapies, it might prevent or slow the development of future therapies for the same condition.
That leaves US lawmakers and regulators with a question to answer: Should the US adopt an EU-styled approach by which rarity is determined as a percentage of the population? Or should the current system be left in place, especially in light of a surge of interest in developing drugs for rare and orphan conditions?
Perhaps it's time for discussion of this potential problem to become a little less rare as well.