Recently there was a national controversy in Belgium over Victor, a 7-year-old aHUS patient. aHus is a rare and deadly kidney disease and requires a treatment every two weeks. This treatment is very expensive and questions arose as to who had to pay for the high costs.

I cannot and I will not answer this question, but I can and I do want to give you more insight into the development of drugs for rare diseases. Because this is an interesting and life-saving industry… an industry which I work in every single day. Welcome to the world of orphan drugs!

From molecule to medicine in 5 phases

The research and development (R&D) of new medicines typically consists of five phases. These consecutive phases are well described and illustrated in the brochure ‘From molecule to medicine’ by Janssen Pharmaceutica.

From Molecule to Medicine - Janssen Pharmaceutica

– Janssen Pharmaceutica


In short, the different phases underlying the research and development of drugs are:

  1. Basic research: where we investigate new ways to fight known diseases or where we screen for new molecules to fight (un)known diseases.
  2. Pre-clinical development: where we turn molecules into candidate drugs that are tested in a test-tube, on cells or on live laboratory animals.
  3. Clinical trials: where we test the candidate drugs on healthy volunteers (phase 1), on a small number of patients (phase 2) and on a large group of patients (phase 3).
  4. Registration: where we submit all the data from the previous phases to the government in order to get official approval to start producing the drugs.
  5. Commercial: where we produce our new drugs, where we introduce them to the medical profession and where we request a price and reimbursement from the authorities.

Every organization that wants to bring a new drug to the market has to go through these 5 phases. By thoroughly testing the efficacy and the additional effects of candidate drugs in test tubes, on cells, on laboratory animals and on the human body, we can make sure that the medicines that make it to the market are safe and effective.

Orphan drugs: Rare diseases call for a different approach

As you might guess, the research and development (R&D) of new medicines is a lengthy and expensive process. This challenge is even bigger if we want to develop drugs to fight rare diseases.

Rare diseases are often deadly and their progress over time is unpredictable. Rare diseases can be very aggressive, calling for repetitive lifelong treatment. When developing drugs for such rare diseases it is typically hard to correlate the effect of the new drugs with the progress of the disease with the patient.

As the term indicates, the number of patients diagnosed with rare diseases will always be limited. As a result there may not be that many patients available at any given moment in time. This raises 2 big challenges with regard to the research and development of drugs for rare diseases:

  • The cost per unit for such drugs is often not commercially viable because the market (the number of patients) is very limited.
  • There may not be enough patients to thoroughly test the drugs through a regular Phase 3 trial as described above.

Fortunately, these two challenges have been recognized by the authorities in Europe and the US. In order to encourage the development of drugs which might otherwise lack a sufficient profit motive, R&D facilities can now apply for an ‘orphan status’ for the research and development of drugs that fight rare diseases.

Orphan Drugs - Pauwels ConsultingIn order to be eligible for the orphan status, a candidate drug has to fight a rare disease that affects fewer than 200,000 people in the United States or not more than 5 per 10.000 persons in the EU.

In late 2007, the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) agreed to utilize a common application process for both agencies. However, the two agencies continue to maintain separate approval processes.

Government support to fight rare diseases

The intervention by government on behalf of orphan drug development can take a variety of forms:

  • Tax incentives: reduced fees for regulatory filings, research grants, and free advice from regulators on designing clinical trials.
  • Enhanced patent protection and marketing rights: Market exclusivity for drugs for 7 years (US) or 10 years in Europe. This prohibits rivals from making the same medicine.
  • Clinical research financial subsidization: Clinical research is sponsored by the government.

These incentives have a positive impact on patients because these incentives allow manufacturers to invest in programs that would otherwise not be commercially viable.

Orphan drugs R&D: agile development under stringent guidelines

My company also develops orphan drugs. As Head of Quality it is my role to protect our patients’ interests as well as my company’s interests. Every day again I strive to find a healthy balance between fast-paced R&D (to help our patients as quickly as possible) and the strict guidelines that are issued by the international authorities (to safeguard the safety of our patients).

It is not the easiest job in the world, but it is a very rewarding one. I am more than happy doing my job as it allows us to serve and cure patients with safe and effective products in the shortest possible time.

Would you like to learn more?

Would like to know more about the development of new drugs? Then keep a close eye on this blog! If you subscribe below, you get all our future blog posts delivered in your inbox as soon as they are published on this website.

Frans Bosselaar - Pauwels ConsultingFrans Bosselaar has been working in the pharmaceutical industry for almost 20 years now. Over the years he has been involved with the production, qualification, validation, supply chain and quality assurance of medicines.

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