Rare disease patients becoming rarer in the USA.

Article No. 427

15 April 2021

It is not surprising that people are confused by rare disease definitions and terms, the aHUS Global Action has featured a number of articles to try to understand them itself.

A recently discovered article from 2015 by the Richter et al, on behalf of ISPOR Rare Disease Special Interest Group, tried to make sense of it all. ( see copy of article HERE) .

The Group  looked at terms used in online literature provided by 32 health jurisdictions from six geographical regions of the world. ” Rare Disease” and Orphan Drug” were by far the most common terms used in a list which included examples such as  “low frequency disease, “ultraorphan disease”, “rare and neglected disease” and “extremely rare disease “( an aHUS Global Action favourite term for aHUS!).

The most popular type descriptor being “rare” and condition descriptor being “disease” ,along with two rarity descriptors ” ultra” and “very”.

They found prevalence thresholds ranging from 5 to 76 persons per 100,000 population. The average being 40 ( a number used by the UK and EU). The USA threshold was higher at 64 per 100,000, i.e  roughly just over 200,000 people in the USA in 2015.

Over the past forty years those with rare diseases have  had much to be thankful for. One of the most influential events in rare disease history was the US Government’s passing of the Orphan Drug Act  in 1983 which was lobbied for by the National Organisation of Rare Diseases (NORD). Apart from the financial provisions to support the development of “orphan drugs” (drugs  for conditions that had no pharmaceutical treatments), the Act put together a first definition of what such conditions were. They were described as those which ” occur so infrequently in the United States”, so that cleared that definition up at the time.

In fairness within a year a further Act , The Health Promotion and Disease Prevention Act of 1984 included an amendment to the wording of the 1983 Act. In Section 4 b of the 1984 Act the amendment struck out “occur so infrequently in the United States” and replaced it with ” which affects less than 200, 000 persons in the United States”. And in time that became what is taken to mean what is  a “rare disease” in the United States.

In fact the Act also provides for conditions affecting more than 200,000 persons in the US  to be orphan  “if  there is no reasonable expectation that the cost of developing and making available in the United States a drug for such disease or condition will be recovered from sales in the United States of such drug”.

And it remains the definition to this day.

In 1983 the population of the US was just over 230 million. In 2020 it is just over 330 million so a rare disease in the USA by the definition in the Act has become relatively rarer from about 1 in 1150 in 1983 to 1 in 1650.

The number of aHUS patients in the USA  has increased since 1983 (no one knows how many there were back then, probably there were very  much less than 100, or  less than 1 in 2.3 million!). Today there are  likely to be somewhere in the region of 2000 to 3000 US  aHUS patients (between 1 in 165,000 and 1 in 110,000).

Eculizumab and Ravulizumab, along with improved renal care generally, making that possible. Those technologies benefited from the 1983 Orphan Drug Act .

aHUS  has some way to go before it breaches the threshold of  200,000 in the population threshold, if ever. Nevertheless becoming a less rare disease when a rare disease in the USA is becoming rarer.