Patient & Physician

Rare Disease

About Rare Disearse

      According to World Health Organization (WHO) standards, rare diseases are defined as a single disease or lesion with a prevalence of 0.65 to 1.00 per 1,000. There are currently about 6,000 to 8,000 rare diseases worldwide, affecting about ca. 350 million people. Rare diseases are mostly caused by specific gene mutations, which usually have the following characteristics: (1) the incidence of a single disease is low and the patient population is small; (2) Genetics is dominant, about 80% of rare diseases are caused by gene mutations, 60% of the diseases occurs in childhood; (3) The diseases have serious consequences, about 90% of rare diseases are classified as serious diseases, the life expectance of ca. 30% of the patients is less than 5 years; (4) Diagnosis is difficult, more than 30% of the patients consulted multiple doctors (5 to 10) doctors; a definitive diagnosis could take 5 to 30 years to achieve; (5) High rate of misdiagnosis, up to 44%; only ca. 25% of the patients received the standard treatments; (6) Low treatability, effective treatments exist only for ca. 5% of the rare diseases, effective drugs exist only for less than 1% of these diseases. Rare diseases also place a heavy financial and emotional burden on patients, their families, and the society as a whole, and are the focus areas of modern medicine with great and urgent unmet medical needs.

Due to the very low incidence and prevalence, the definition of rare diseases varies from country to country, mostly by epidemiological criteria, disease severity, orphan drug economics criteria as follows: United States: the number of patients less than 200,000; EU: disease prevalence of less than 1/2000; Japan: diseases with fewer than 50,000 (or 1/2500); Taiwan, China: Diseases prevalence of less than 1/1000. Currently, China does not have a legal definition of rare diseases. The Chinese Medical Association in 2011 defined that, in China, diseases with the prevalence of 1 in 500,000 adults, and diseases (usually genetic in nature), diagnosed in newborns with an incidence of 0.1 per 1,000 births or less, could be considered a rare disease. Most rare diseases are due to gene mutations and are generally not curable with conventional treatment options.

The management of rare diseases depends on multiple infrastructural supports, including the knowledge and experience of health care professionals regarding rare diseases, rapid and reliable diagnostic techniques, innovations in drug discovery and development, and compliant manufacturing, etc.

Orphan drugs are diagnostic reagents, vaccines, drugs, and medical devices used to diagnose, treat or prevent rare diseases or rare medical conditions. Because orphan medicines are in different development stages in different countries, the definition of orphan drugs is not always consistent among these countries. In the United States and Japan, orphan drugs refer to drugs, biological products, medical food and medical equipment. In the European Union and Australia, orphan drugs range from medicines and biological products, but do not include medical devices, food and nutritional supplements. China does not have a formal definition yet.

Currently the world's top 10 best-selling orphan drugs are for cancers or blood cancer subtypes. Approximately 30% to 40% of orphan drugs approved by FDA are anti-cancer drugs. Orphan drugs have the advantage of shorter clinical trials associated with lower cost, faster approval, high drug prices, could partially offset the smaller patient population and bring reasonable financial returns for pharmaceutical companies. In addition, most rare diseases do not have effective drugs available. Therefore, the urgent medical needs and market demand, relatively speaking, predict a larger growth space and less fierce market competition for orphan drug developers. Consequently, to win approval first as an orphan and then expand to non-orphan disease indications, had evolved into an important and profitable drug development strategy for large pharmaceutical companies in the United States and Europe. This contributed to an increase in the number of marketing approvals for orphan drugs/medicines in developed countries year-over-year. It is projected that by 2020 the global sales of orphan drugs will reach 178 billion U.S. dollars.

Drugs for rare diseases in China or are largely imported and their accessibility by patients is relatively low. The discovery and development of orphan drugs in China is still in its infancy. Thus, we need to closely follow the development and regulatory status of orphan drugs already in later stage development or already marketed outside China and attempt to meet their domestic needs by adopting a diversified strategy in use of flexible research and development methods, such as, independent discovery and development, collaborative development, the license-in of drugs marketed or those in later stage clinical testing, as well as a combination of the above-mentioned strategies, focusing on developing orphan drugs that affecting a relatively larger patient population with seriously/devastating health consequences but without effective treatment options.

As an indication of the success of the 1983 Orphan Drug Act in the United States, more than 420 orphan drugs and biologic products for rare diseases have been approved by the Food and Drug Administration (FDA), compared with fewer than 10 such products in the decade before the Act. Similarly, since 2000, when the European Union (EU) established procedures for orphan drug application and incentives for development in their EU Regulation on Orphan Medicines(EC/141/2000) to address rare conditions, 84 orphan drugs have received market authorization by the EU Commission, 2 of which were subsequently withdrawn [4]. Increased attention on rare diseases has also resulted from an improved genetic, molecular, and biochemical understanding resulting from recent scientific and technological advances. Social awareness uptake and global connectedness in the area of rare diseases is noticeable. For example, when the first Rare Disease Day began in 2008, only18 jurisdictions participated compared with 84 in 2014.