Rare diseases - still rare disease, but no longer orphans

Written by Dr Peter Adura, Director, Medical Services

Historically, rare diseases were also called orphan diseases. They were orphans because no one was developing therapies for them. There was no chance that a company would be able to recover its investment if it spent time and money developing a treatment for such a small population. Some of these diseases are no longer ‘orphans’ in this regard, because the bio-pharmaceutical industry is now ‘adopting’ them slowly, but steadily. Nonetheless, rarity remains the defining feature of these diseases. In fact, the US Food and Drug Administration (FDA) defines an orphan drug thus: ‘the number of people affected by the disease or condition for which the drug is to be developed is fewer than 200,000 persons; or there is no reasonable expectation that the sales of the drug will be sufficient to offset the costs of developing the drug for the U.S. market and the costs of making the drug available in the United States’[1]. The European Medicines Agency (EMA) has a similar approach - the prevalence of the condition in the EU must not be more than 5 in 10,000 for it to qualify for orphan status[2]. The FDA and the EMA therefore decided to make research in this area economically viable with tax breaks and other incentives. So, paradoxically, on the one hand companies first must show that the conditions are orphan conditions, then do the research to avail themselves of the incentives – but then technically these aren’t orphans anymore …

So, rare disease/orphan disease/orphan drug research are used interchangeably, understandably. At Cmed, we prefer the term rare diseases – it is accurate and unambiguous.

The major challenges with rare disease studies are the small number of viable patients, their wide geographic spread, and the small pool of therapeutic experts available who treat the disease. Such trials can also be relatively costly - considering the small number of patients involved, there are no precedent products upon which to base decisions, and trials often have challenging logistical and resource requirements.

As such, sponsors of orphan drug research often have limited previous experience, and most of the time, the regulatory authorities also have little experience with that particular indication. The sponsor is therefore in a position of having to truly trail blaze, learn from the process, and take the regulatory authorities on the same learning journey.

Selecting the right CRO to be a partner on that journey might be the most critical decision facing sponsors. Anyone who has worked in the rare disease space will agree that every trial involving rare diseases has a unique set of medical, scientific and operational challenges and requires a very tailored approach. The selected CRO needs to be both experienced and street-wise in the conduct of these studies.

In my experience, a CRO with a solid level of experience in designing and delivering studies in rare diseases, or in studies in which patient populations are difficult to recruit, will help optimise protocol design, gain access to Investigators and subjects, and allow for a successful clinical trial. I believe it is essential for a CRO to:

  • Put in the time to create strong relationships and make the study procedures as efficient as possible.
  • Offer additional site management support if needed, including more visits to the site.
  • Make sure that the right patients are enrolled in the study. Since every data point counts in a rare disease study, ensuring appropriate eligibility is critical.
  • Provide clinical teams to work with the site who are highly skilled in areas such as data collection mechanisms, helping to ease the site burden.

This type of research is essential, exciting and hopeful. That’s why I’m pleased to play a part in finding novel solutions to the unique problems posed by rare diseases. At Cmed, we can call on our wealth of experience and transferable skills from working on other rare disease studies, we have extensive experience from previous interactions with the regulatory authorities on rare diseases, and we have come to know what they’re looking out for.

  1. FDA - Designating an Orphan Product: Drugs and Biological Products
  2. EMA – Orphan Designation