Published online 2 February 2009 | Nature | doi:10.1038/news.2009.75
Corrected online: 4 February 2009


Rare diseases, rarer treatments

Are European attempts to encourage drug development working?

Pills and other medication.There are concerns that too few drugs to treat rare diseases are being approved in Europe.Punchstock

Europe's attempts to encourage the development of drugs for rare diseases have failed, according to a new study.

Only 44 drugs for rare diseases were given marketing approvals in the European Union (EU) between 2000 and 2007. This is despite a package of incentives being adopted in 2000 to spur the development of treatments for 'orphan diseases', which affect fewer than 6 in every 10,000 people.

"It is a cause for concern that in spite of an ad hoc law, after eight years orphan drugs in the EU are still few and poorly studied," write Roberta Joppi, Vittorio Bertele and Silvio Garattini, all from the Mario Negri Institute for Pharmacological Research in Milan, Italy, in a new paper in the British Journal of Clinical Pharmacology1.

They report that 500 drugs cleared the first hurdle to approval and were given 'orphan designated status' — which recognizes a drug's potential benefit and qualifies its developer for incentives such as reduced fees, help with submissions and ten years of market exclusivity. However, only 44 drugs had actually been approved by the time the paper was written, a number that has since risen to 50.

In reviewing the approvals, Joppi and her colleagues also found potential problems with the clinical data used to support applications. In a number of cases, they say, the length of the trial was too short in relation to the natural history of the disease in question. Several trials were also tiny, involving fewer than 100 people. Although for some rare diseases this is acceptable, says Joppi, in other cases — such as Fabry disease, which causes a type of fat to accumulate in blood vessels and other organs — the pool of patients is big enough for larger and better trials.

The study follows up on the team's previous work, published in 2006, which first suggested that the new laws might not be having the intended effect2.

"The second time we approached the problem, we hoped the situation would be different but it wasn't," Joppi told Nature News. "There are a lot of designations but the number of approved drugs is small. The consequences are that the patients are without any treatment."

Hasty verdict?

Not everyone agrees with the researchers' conclusions.

In a statement to Nature News, the European Medicines Agency (EMEA), which provides opinions on approvals for the EU, said: "The general opinion amongst the rare disease community, and indeed amongst patients, is that the EU Orphan Regulation has been an unprecedented success and has triggered a wave of development of medicines in the field of rare diseases. There are data indicating that the average time from designation to authorization is 4 years (+/- 3 [years]) in the USA, therefore after nine years of the implementation of the regulation in Europe it would be unrealistic to expect a massive increase in authorized orphan medicinal products.


"It is encouraging that 621 medicinal products have been designated and the vast majority of them are under active development."

Emmanuel Chantelot, executive director of the industry group European Biopharmaceutical Enterprises, also believes it's too early to judge whether the incentives are working.

"The regulation is only nine years old, and 50 drugs approved and 500 drug designations isn't too bad," he says. "It has done a lot to support R&D in the field of rare diseases."

Christopher Milne, associate director of the Tufts Center for the Study of Drug Development at Tufts University in Massachusetts, also says the paper is perhaps "overly harsh" on the European system.

However, Milne does believe the development of orphan drugs requires more assistance. "With the whole economic situation, I think the public-sector funding is going to take a much greater role, probably more so in Europe," he says.

The European Commission last year issued a recommendation for a European Strategy on rare diseases, which included suggestions for encouraging cooperation between researchers and national plans for increasing research. 


The EMEA initially incorrectly quoted the number of medicinal products that have been given orphan status as 900. The article has since been corrected with the actual figure of 621.
  • References

    1. Joppi, R., Bertele, V. & Garattini, S. British Journal of Clinical Pharmacology doi: 10.1111/1365-2125.2008.03369.x (2009).
    2. Joppi, R., Bertele, V. & Garattini, S. Br. J. Clin. Pharmacol. 61, 355–360 (2006). | Article | ChemPort |
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