Surely you have seen at least once on social media the post of frightened parents begging for help. If you paused for a moment and read the message, you’ve probably come to the part: “Our daughter/son suffers from a rare disease and the medicine is too expensive, and therapy is only possible in the USA. Please help… ”And then the information about the bank account followed and you probably just continued to casually browse the posts on the Facebook feed.

Have you thought about the other side of the story? Why would medicine be so expensive and unattainable for a sick child? Does the post really contain true information, were you supposed to help desperate parents? The answer to all your questions, but also to the questions of hopeless family members of the patient, lies in the researched, but less popular topic –  “orphan” drugs.

Rare diseases and their therapy

Each state, depending on the population, determines individually what is considered a rarity. Also, for example, WHO (World Health Organization) considers a frequency of less than 6.5-10 per 10,000 people to be rare, while the European Union considers a frequency of less than 5 per 10,000. Precisely because of the very small number of patients with such clinical pictures, these patients are called “orphans”, and the drugs used in therapy – orphan drugs.

These are most often congenital or genetic disorders, but malignant and autoimmune diseases, poisonings, and rare infections are also members of this group of medical conditions. Although at least 7 000 rare diseases have been detected so far, their exact number is still unknown, and the first symptoms usually appear in early childhood.

Orphan drugs

Apart from the fact that they are intended to treat the hitherto incurable, their important feature is the high price. To be more detailed, it can take ten years from the discovery of a molecule that could potentially represent a new drug, to clinical trials. If we add up all the costs needed to conduct studies and research the properties of the molecule, we would come up with a high amount of money that a pharmaceutical company must spend to develop any new drug on the market.

Also, all those ten years can fall into the water if unwanted side effects are noticed during preclinical trials, most commonly in mice. Therefore, to compensate for the cost of developing an orphan drug, the same drug has an extremely high and even unattainable price.

Impact on the development of pharmaceutical companies

Given the aforementioned facts about the high consumption and length of the procedure, no company would voluntarily agree to the development of orphan drugs. Namely, in the period between 1970 and 1980, only 10 new drugs for rare diseases were discovered, so in 1983 the Orphan Drugs Act, called the Orphan Drug Act (ODA), was passed.

This gave pharmaceutical companies financial support to develop much-needed drugs. For example, non-returnable funds for research and development and tax relief were just some of the benefits to encourage as many industrially important institutions as possible to research and study new molecules, potential drugs, in a relatively short period of time.

What is the situation today? FDA ( The Food and Drug Administration) has approved less than 500 orphan drugs to date. Their development is not stopped or slowed down, but in order to reduce costs, previously known molecules with a hitherto unrelated target site of action are studied. In the past three decades, of the total number of new drugs on the market, more than 40% are orphan drugs. Moreover, recent studies have identified 800 potentially important compounds, of which at least 40% have shown possible use in the treatment of rare diseases.

Will we be able to eradicate rare diseases with newly discovered drugs? Unfortunately, despite the development of biomedicine, the number of rare diseases is growing day by day. Currently, in the period from 2017 to 2022, it is planned to increase the number of relatively available therapies by 11.1%, and in the long run, 30% of upcoming projects are related to extremely rare conditions. Also, it is considered that more incentives are needed so as not to deprive the remaining patients, who do not suffer from rare diseases. Although orphan drugs are not the biggest source of profit for larger companies, everyone has the right to appropriate therapy, regardless of the difficulty of the path to drug discovery.

Tumors and orphan drugs

Cancer patients, as well as their conditions, have always been a separate medical group. Among other things, most orphan drugs are intended to treat tumors. Given that nearly two hundred types of rare tumors were detected, it is not surprising that between 2012 and 2013, the number of approved oncology drugs was the same amount as the sum of drugs for all remaining patient groups.

Why oncology? Primarily, it is the medical field with the most unknowns, challenges, but also rare conditions, mostly from the hematological aspect. It is also an area where manufacturers divide patients into additional subgroups and want to create an orphan drug for each, and of course, they need to get a financial incentive for that. Precisely because of this, since 2013, the FDA has not considered different stages of the same tumor to be separate groups. For example, trastuzumab is a drug that has been denied orphan status by the FDA. Namely, during the evaluation of products intended for the treatment of breast tumors, it considered the first stage of HER-2 positive breast tumor to be the same therapeutic group as the fourth stage.

Furthermore, once the tested molecule shows a good therapeutic effect for one type of tumor, its effect on the remaining types can be tested. This increases the target group of action, expands use, and thus increases earnings. Finally, the role of pharmacogenomics is also indispensable. During testing, patients who are more likely to create a particular response to a drug may be genetically tested, which can be crucial during the discovery of new tumors.


CLL (chronic lymphocytic leukemia) is a B-cell lymphoproliferative disease characterized by small round clonal lymphocytes that affect the peripheral blood, bone marrow, lymph nodes, and spleen. Since this is the most common leukemia of old age, new discoveries are very important, as well as advances to treatment without chemotherapy. It is a new period of treatment that has started venetoclax, one of the orphan drugs.

It acts as a selective inhibitor of the BCL2 ( B-cell lymphoma 2) pathway responsible for initiating oncogenesis, disease progression, and drug resistance. Accelerated apoptosis of CLL cells was shown but without a decrease in platelet levels, which was an improvement over previous therapy. Due to its effective action, the FDA has approved the accelerated procedure venetoclax as an orphan drug. However, as it is not approved by the European Medicines Agency, it is not available in Europe – hence the famous sentence: “Therapy is only possible in the United States.”

Myths about orphan drugs

1.7 of the 10 best-selling drugs in the United States are orphan drugs.

Namely, such drugs have several indications, they are not sold only as orphan drugs. They are approved for the treatment of a number of different medical conditions, not just rare diseases. Therefore, their sales are high precisely because of the wide range of activities. Adalimumab, a drug that is often “accused”, has 12 different uses. Only a third of the applications are intended for the treatment of rare diseases. Of 13, 6 billion dollars, which is the total sales of this drug during 2016, only 3,8% stems from orphan indications.

2. Indications to treat rare diseases are being added to existing drugs on the market to overtake their rivals.

If the drug is already on the market and the manufacturer receives approval for an additional indication – treatment of rare diseases, it must take 7 years from the approval for this drug to be exclusive to its new role.

3. Orphan drugs are the main culprits in the increase in health care and treatment costs.

Of the total $450 billion earned from drug sales in the U.S. in 2016, only 7.9% (35.5 billion in revenue) is made up of orphan drugs.

4. Special medicines are the same as orphan medicines.

Special drugs are defined by their special release, storage, or price. Orphan medication can be counted as special, but not all special medications are actually orphan medications.

5. The Orphan Medicines Act distracts research and the market from diseases that affect more people.

The study of rare diseases has resulted in a better understanding of the body’s biochemical processes and has led to incredible insights into the interaction of our genes and growth factors, thereby causing disease. The Orphan Drugs Act has contributed to innovations in most treatment methods, including tumor therapy.

The most famous orphan drugs


Its importance is so great that it is considered “the” orphan medicine. Ivacaftor was the first preparation to act on a genetic disorder that precedes the onset of cystic fibrosis. Although once used only in patients with the G551D mutation, one of the most common disorders, since 2018 it has also been used in the treatment of patients 12 months and older who have a single mutation in the CFTR gene, which encodes a transmembrane conduction regulator for cystic fibrosis (CFTR).


Intended for the treatment of blood cancer, lenalidomide became a blockbuster with earnings of almost 4 billion in 2012. It is approved in combination with dexamethasone in patients with multiple myeloma, but also patients with anemia caused by the myelodysplastic syndrome.

No matter which side of the “scenery” you are on, no person deserves to fight for their own health as a “fight against windmills.” That person whose life hangs in the balance can become any of us. And at that moment, everyday worries disappear, the primary goal is healing. But if the rescue is across the ocean or costs hundreds of thousands of dollars, will the patient be able to save himself? On the other hand, can we expect lower drug prices, without the classic drugs intended for “ordinary” headaches? Reviewing doesn’t make sense, but frequent checkups do.

Take care of yourself, report any changes in/on your body to your doctor, no matter how many times you have to call to get an appointment. At best, therapy will be at your fingertips, but individuals will not. For all of you who suffer from rare diseases or know such a patient – do not allow yourself to be ridiculed because posts on social networks are the only way to raise funds. Fight, in any way, and don’t give up regardless of obstacles along the way. You have the right to treatment, to a new morning in a warm bed while breathing with full lungs and living a normal life, full of “unimportant” worries.

Translated by: Ines Jurak

Literature sources

Aronson JK. Rare diseases and orphan drugs. British Journal of Clinical Pharmacology, 2006, 61 (3), 243 – 245.

Orphan Drugs & Rare Diseases. 2020,, accessed 12 October 2020.

Attwood MM, Rask Andersen M, Schiöth HB. Orphan Drugs and Their Impact on Pharmaceutical Development. Trends in Pharmacological Sciences, 2018, 39, 525 – 535.

Korchagina D et al. Orphan Drugs in Oncology. Recent Results in Cancer Research, 2019, 213, 109 -142.

Milunović V et al. Are we entering an era without chemotherapy in chronic lymphocytic leukemia? The role of ibrutinib and venetoclax, ie lessons learned from idelalisib. Acta Medica Croatica, 2017, 71, 95 – 106.

5 Myths About Orphan Drugs and the Orphan Drug Act,, accessed 15 October 2020.

Top 20 orphan drugs by 2018, 2013,, accessed

October 16, 2020. List of FDA Orphan Drugs,, accessed October 16, 2020.


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