More to OD development for ultrarare metabolic disorders than meets the eye

In the last 60 years the number of ultrarare metabolic disorders (prevalence: <1 patient/100,000 inhabitants) has grown considerably. The question I raised was whether orphan drug development can keep up with this pace ? I raised the question, because there doesn’t seem to be an end to the growth. An excellent comment was made by José Jorge Galán Retamal and his concluding remark was that orphan drug development cannot keep up with rare disease research pace. I have to agree.

bit of history.....Joseph Merrick lived at the end of the 19th Century in Great Britain. The exact cause of Merrick's deformities remains unclear. For a long time it was believed he suffered from neurofibromatosis type I and/or Proteus syndrome. Genetic testing has proven inconclusive (source: Wikipedia

However, it’s one thing that orphan drug development can’t keep up, it’s quite another if there is no orphan drug development at all. Like many of you, I am aware that the latter is certainly not the case. The FDA published a quantitative assessment of the first 25 years in Nature Reviews Drug Discovery. To get some feeling whether or not orphan drug development is happening for ultrarare disorders, I reviewed the US and EU orphan drug databases (FDA; EU). I was able to positively identify several ultrarare metabolic disorders with a US or EU-designated orphan drug. For some even a product was approved

I may have missed a few, but the important message here is that orphan drug development for ultrarare metabolic disorders is taking place, and some have even made it to the patient (!).

How well these products work in real life is certainly not unimportant, but subject for another post. Moreover, the story doesn’t end here, because many ultrarare metabolic disorders remain without treatment, what to do about it:

  1. We need to start taking into account the specific characteristics of ultrarare (metabolic) disorders in the drug approval process. Luckily there are people out there that are trying to achieve this. Their efforts have resulted in important legislative steps that will hopefully come into force in the US soon: the ULTRA act and the TREAT act. For more on this subject: I can highly recommend a wonderful paper by Kakkis & Miyamoto in OJRD. Another one that is just out there: Adaptive Licensing: Taking the Next Step in the Evolution of Drug Approval with authors from regulatory bodies, industry and academia!
  2. What I am interested in is to determine what distinguishes ultrarare metabolic disorders with orphan drug development from those without. I believe what I have found is only the tip of the iceberg. When I started to look for patient foundations that raise and provide funds for research, I came across a number of interesting therapy development programs that have not yet resulted in a US or EU-designated orphan drug. Moreover, although not surprised, I am really impressed by the overwhelming number of patient-initiatives. Some raise funds, others have moved on to the next level and started their own company (Niemann Pick C – Addi & Cassi Fund), their own research institute (Krabbe disease – Hunter’s hope foundation) or biobanks and registries (Genetic Alliance).
  3. Until now we have only discussed ultrarare metabolic disorders. Together with oncology, rare metabolic disorders have attracted quite some attention from research as well as industry. We also need to consider the situation for other ultrarare disorders, like neurology, cardiology, congenital malformations, etc. There the story may be completely different.

To read more on this subject:


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