Orphan Drugs Around the World – Current Situation and Future Perspective of New Markets

by Marietta Seuß

Marietta Seuß summarizes the situation of orphan drugs in the US and other countries and explains the incentives for developing orphan drugs such as the Rare Pediatric Priority Review Voucher in the US.

What are orphan drugs and why are they important?

Orphan drugs (ODs) which are used for the treatment of rare diseases are often not developed or marketed because their extremely limited use makes them unprofitable. Well known examples for rare diseases are Duchenne Muscular Dystrophy, Gaucher Disease and Narcolepsy.

More than 7,000 established rare diseases are known, and the number is increasing as 250 new rare diseases are recognized every year on average. About one in ten people in the world suffer from a rare disease, of which between 85% and 90% are serious and often life-threatening.

The classification of a rare disease varies across continents, countries and regions. While a disease may be classified as rare in one country, it may be more prevalent in another country or not classified as rare because of different medical definitions.

Although there are thousands of rare diseases and numerous groups and organizations to support patients, the awareness of rare diseases can often be low. Patients may have difficulties obtaining a correct diagnosis and locating disease information and support, and their treatment options can be limited, unavailable, or even non-existent.

Orphan Drugs in the US: FDA’s ODA

In 1983, the US took a first step to meet people’s needs: the Orphan Drug Act (ODA) was established. Based on this law, the developing company of an orphan drug can rely on numerous beneficial incentives when bringing an orphan drug to the market.

These include:

  • Government incentives, e.g. tax credit, grants, waved application fee
  • Small size and fast track approval of clinical trials
  • Higher regulatory success than non-orphan drugs
  • Premium drug pricing
  • Less approval hurdles
  • Less marketing expenditure
  • Orphan drug exclusivity
  • Multiple orphan disease approvals

There have been more than 2,000 applications to the Food and Drug Administration (FDA), of which about 553 orphan drug products have been approved, as indicated in Figure 1. Over 700 clinical trials have been funded by the Orphan Products Grants Program to date.

Figure 1: Number of orphan product designations and approvals by FDA until 2016 (Rana & Chawla, 2018)

A Special Case – the Rare Pediatric Priority Review Voucher in the US

For certain medicinal products, the FDA accelerates its regulatory review with the intention to get them to the market more quickly. For companies, FDA’s priority review process means they can market their product faster.

FDA’s priority review vouchers are incentives meant to spur the development of new treatments for diseases that would otherwise not attract development interest from companies due to the costs of development and the lack of market opportunities, including rare diseases.

To do this, companies are given a special voucher which allows them to have any one of their medicinal products reviewed under FDA’s priority review system.

There are different types of review vouchers:

  • Tropical Disease Priority Review Voucher
  • Rare Pediatric Disease Priority Review Voucher
  • Medical Countermeasure Priority Review Voucher

For example, under the program of the “Rare pediatric Priority Review Voucher”, a sponsor who receives an approval for a drug or biologic for a “rare pediatric disease” may qualify for a voucher that can be redeemed to receive a priority review of a subsequent marketing application for a different product. The voucher is issued by the FDA at the time of the marketing authorization. The application does not have to meet the usual requirements for a priority review, but it must be submitted after the approval of the rare pediatric disease product application.

The application relies on clinical data derived from studies examining a pediatric population and dosages of the drug intended for that population. However, an applicant cannot receive a rare pediatric disease priority review voucher if the application seeks approval for an adult indication in the original rare pediatric disease product application.

Orphan drug acts in other countries

Other countries soon followed the American example and released similar acts:

  • Singapore (Orphan Drug Exemption to the Medicines Act, 1991)
  • Japan (Orphan Drug Amendment to the Pharmaceutical Affairs Law, 1993)
  • Australia (Australian Orphan Drugs Program, 1997)
  • South Korea (Orphan Drug Act, 1998)
  • European Union (Regulation 141/2000 in the Official Journal of the European Communities, 2000)
  • Taiwan (Rare Disease and Orphan Drug Act, 2000)

Out of 2,884 applications 1,911 obtained an orphan drug designation, and 137 orphan products have received marketing authorization in the European Union since 2000.

Until December 2016, the Ministry of Health, Labor and Welfare (MHLW) in Japan has designated 336 products as orphan drugs. Of these, 276 have been approved for marketing.

In 2017, the Taiwanese government officially categorized 209 diseases as “rare diseases”. So far, 74 orphan drugs and 40 special nutrients have been approved by the government for treatment of patients.

At present, 184 orphan drugs have been approved by the Korea Food and Drug Administration (KFDA) in South Korea.

Other countries like the Philippines, China, Thailand, and India are also currently considering orphan drug legislations.

What kind of ODs are on the market in the US and the EU?

A raising number of companies develop orphan drugs and the variety of product classes represented in this category is growing. Biologics, rare cancer treatments, and targeted therapies are reflected in an increasing proportion of orphan drug approvals over time. About 40%-60% of the total orphan drugs approved in the USA and in the European Union (see Figure 2 for the top 20 EU orphan designations) are intended for cancer and metabolic diseases.

Figure 2: Top 20 EU Orphan Designations (“Orphan drugs | Contract Research Organization | Poland | Clinical Consulting”)

Orphan drug research highly supports common drug research

In the past, clinical research on rare diseases often contributed to the understanding of common diseases, too. For example, research on the Tangier’s disease which is characterized by a complete absence of plasma high density lipoprotein (HDL) helped for building therapies to decrease cardiovascular mortality. The basic and clinical research on rare diseases will certainly also enhance our existing knowledge about many common disorders in the future.

Biopharma Excellence is experienced in the area of orphan drugs and in writing applications for orphan drug designation. For further information on our services regarding orphan drugs and orphan drug designations, please do not hesitate to contact us



  • Orphan drugs | Contract Research Organization | Poland | Clinical Consulting. Retrieved April 23, 2018
  • Rana, P., & Chawla, S. (2018). Orphan drugs: trends and issues in drug development. Journal of Basic and Clinical Physiology and Pharmacology, 0. doi:10.1515/jbcpp-2017-0206