Orphan drug approvals: 2018 set new record for the EMA, but some red flags

In 2018, the European Medicine Agency (EMA) issued 84 positive opinions on new medicines. While the total number is lower than the year before, when 94 programs received approvals, the number of drugs being approved for the first time in Europe was higher than in 2017 (42 versus 35), meaning that there was more innovation reaching the market. 

In this month of February, when we celebrate and promote awareness on rare diseases, I would like to review how 2018 looked when it comes to orphan drug approvals, and orphan drug designations (data from the EMA).

orphan drug designations Europe 2018

The first observation that stands out when looking at the graph of orphan drug designations in Europe is a notable drop in the last two years when compared to the previous trend (Aqua). 

The second observation is the progressive increase in orphan drug approvals (yellow), although quite far from the number of orphan drug designations being issued.

Let’s discuss those two trends and what they might mean about the future of orphan drugs in more detail.


2018 Orphan Drug Designations

While we often refer to them as orphan drugdesignations and orphan drugapprovals, these are the notations used by the FDA. In fact, the EMA and the European Commission (which is the ultimate organism authorizing a drug approval) prefer to talk about “orphan medicinal products” instead. 

The number of orphan medicinal product designations has grown much since the process was started in 2000, and reached a peak during the years 2014-2016 with designation numbers of around 200 per years. While the drop in 2017 to numbers just shy of 150 could have been a fluke, 2018 has confirmed the decrease in the number of drugs obtaining the orphan status, indicating there might be some difference in the trend.

One possibility is that the decrease in orphan designations is due to a decrease in the number of applications. However the number of designations (successful applications) in 2017-2018 is comparable to 2012-2013, yet the number of applications was 25% higher in 2017-2018 meaning that the success rate was lower.   

A breakdown of these numbers indicates indeed that the success rate as decreased, and in the recent years the percentage of successful orphan applications has gone down from about 70-76% to a recent low of 59% in 2017. However 2018 has returned to the rate of previous year with 67% of the applications receiving a favorable opinion. Therefore, a reduced success rate due to the EMA becoming stricter or applications becoming weaker cannot fully explain why for the last two years we are seeing a substantial decrease in the number of orphan medicinal product designations in Europe. 


2018 Orphan Drug Approvals

The number of orphan drug approvals in Europe continues to experience a progressive increase over the years. In the last 5 years, for example, we had an average of 18 approvals of orphan drugs year, up from 7-8 during the previous ten years.

The actual number of orphan medicinal products is a bit smaller. For example, in 2018, a total of 21 orphan medicinal products were approved for a total of 26 orphan therapeutic indications, meaning that some drugs had approvals for multiple rare diseases.

Both of these numbers, 21 orphan medicinal products approved for 26 orphan therapeutic indications, are a record, exceeding any previous year and making 2018 the best year for orphan drug approvals in Europe.

The upward trend in the number of new orphan drug approvals does not reflect the regression in the number of designations experienced during 2017 and 2018. This is possibly due to the fact that most products receive the orphan drug designation years before they get approved, and raises the question of whether we could expect to see a decrease in the number of orphan drug approvals as soon as the smaller generation of “2017 and 2018 designations” reaches the finish line. 

Therefore, although 2018 was a record year in orphan drug approvals in Europe, it is expectable that we will see some reduction in the next few years.


2018 – US FDA vs EMA

2018 was the best year for orphan drugs in Europe, with 21 different drugs obtaining marketing authorization for 26 orphan indications. Yet when we compared these numbers with the orphan marketing authorizations issued by the FDA during the same time period the European numbers are dwarfed. Year after year, the number of orphan drug approvals in Europe is only one fifth to one third of the number of drug approvals in the US. 

orphan drug approvals Europe 2018

It is also clear form the graph that the lengthier approval process in Europe is not responsible for these lower numbers, since the dips and peaks of both graphs are identical and do not suggest a simple delay in Europe. 

As an advocate for the rare disease patient community in Europe, these numbers worry me and trigger more questions than they address. For example, what does this mean for patients with rare diseases in Europe? Are they accessing the US-approved drugs through some medication import mechanisms or are we looking at a massive drug access problem in Europe? We need to also take into consideration that these graphs represent only central approvals, and that each country in the EU has to give the manufacturer green light to launch in that country, which due to price negotiations or poor market outlook is limited to only a fraction of the countries in the EU.


In summary:

  • 2018 was a record year of orphan drug approvals in Europe

  • The trend matches the US trend, also with a record of approvals in 2018

  • However the number of orphan drugs approved in Europe is much smaller than in the US, meaning less options for patients

  • The number of orphan drug designations (before approval) in Europe has fallen in the last two years

  • If orphan designations represent an early marker of the orphan drug development trend, then we might expect a decrease in the number of approvals in the immediate future

 Ana Mingorance, PhD