english.prescrire.org > Topics > Advancing healthcare policy > Advancing healthcare policy in Europe: a chronological recap of actions > 2019 Recap > Orphan drugs: affordability is at risk due to abuse of orphan drug incentives (4/2019)

Advancing healthcare policy

Advancing healthcare policy in Europe: a chronological recap of actions

A recap of actions in 2019
Orphan drugs: affordability is at risk due to abuse of orphan drug incentives (April 2019)

Paris, 25 April 2019

In its response to the public consultation on the European Commission's guideline on orphan drugs, Prescrire encourages the Commission to pay particular attention to the extreme profitability of certain orphan products, and to better consider alternative treatments such as off-label use or magistral formulations.

> Download Prescrire's response (pdf, 196 Ko)

Prescrire's response to the public consultation

Guideline on the format and content of applications for designation as orphan medicinal products, and on the transfer of designations from one sponsor to another (1)

General comments

Over the last years exorbitant prices of orphan drugs have made the headlines in the media and initiated heated debates over patients' access, affordability and sustainability of healthcare systems. Some voices came up to call for an end to the abuse of orphan drug approvals.

Since the adoption of the orphan drugs Regulation in 2000, pharmaceutical companies developing orphan drugs enjoy regulatory and financial benefits including an accelerated marketing authorisation process, 10 years market exclusivity, the possibility of conducting small and therefore generally less costly clinical trials as well as other advantages. The development of drugs with a favourable harm-benefit balance for patients with rare diseases and no other therapeutic options is clearly welcome. Over the years, the development of orphan drugs has become a very attractive business. In the past several years, orphan drugs accounted for a particularly high proportion of newly authorised drugs and indications, i.e. 22 out of 99 as assessed by Prescrire in 2018. Among these 22 assessments, Prescrire rated 11 drugs or new indications as an advance, but in most cases only a minimal advance. One new orphan drug was considered more dangerous than useful and was added to Prescrire's list of drugs to avoid: obeticholic acid (Ocaliva°) in primary biliary cholangitis. For 4 new orphan drugs, we obtained insufficient data to determine the harm-benefit balance.

Some orphan drugs benefit from subsequent marketing authorisation in several indications. In 2018, lenalidomide (Revlimid°) was authorised in a third indication as an orphan drug for patients with multiple myeloma, after being granted orphan drug status for certain types of myelodysplastic syndrome and lymphoma. In 2015, lenalidomide was the ninth highest selling drug in the world, with global sales of 5.8 billion US dollars. As regards Orphacol° (cholic acid), one year after its approval for two rare bile acid deficiencies, an EU marketing application was filed for Kolbam° (cholic acid) in three other rare bile acid deficiencies. This raises the question whether the orphan drug status is granted too generously, which could lead to an "abuse" of the orphan drug incentives.

Due to their very high prices, orphan drugs raise the problem of affordability and ultimately of patient access. We consider that the European authorities have a duty to pay attention to the affordability of orphan drugs, which should be addressed in some sections outlined in this guideline. The sections on "Medical plausibility" and "Other methods, for diagnosis, prevention or treatment of the condition" deserve special consideration especially regarding the aspects linked to "orphanisation" and magistral formulations.

We invite the European Commission to pay particular attention to the following aspects when finalising the guideline:

  • The number of patients concerned by the disease which can vary from very few to many patients. It is time to reconsider the notion of "rarity".
  • The phenomenon of "orphanisation" of common disorders and the endless research of subgroups where the product might be helpful.
  • The profitability of orphan products, considering multiple orphan indications approved for a given product, and the related R&D costs, including support from public funding or experience with previous treatment use e.g. through off-label use or "magistral" / "officinal" formula.
  • The expected benefits to the patients, including existing alternative treatment methods.

Prescrire's detailed comments available here:

> Download Prescrire's response (pdf, 196 Ko)

©Prescrire April 2019

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