The Dilemma with Orphan Drugs - Pharmaceutical Technology

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PharmTech Europe

The Dilemma with Orphan Drugs
Orphan drugs for rare diseases are a major area of investment for pharmaceutical companies, but are they becoming too expensive for Europe to afford them?

Pharmaceutical Technology Europe

The case of Firdapse

In 2009, Firdapse, which contains the active substance amifampridine, was approved in the EU as an orphan drug for Lambert-Eaton myasthenic syndrome. However, a 2012 paper in the Orphanet Journal of Rare Diseases suggests that the branded product represents a slight modification of an unlicensed and low-priced compound that has been available for several decades (3). The unlicensed drug is 3,4 diaminopyridine (base form) whereas Firdapse is the phosphate-salt formulation of 3,4 diaminopyridine (7). It was suggested that the pricing of the Firdapse was 50- to 70-fold higher compared to the unlicensed formulation (6).

This issue prompted a number of physicians to write an open letter in the British Medical Journal (BMJ) to UK prime minister David Cameron complaining about the way in which companies were unfairly using orphan-drug legislation to their advantage (8). A series of exchanges between BioMarin, the manufacturer, and the signatories to the BMJ letter took place, culminating in the lead author writing an FP10 prescription for the cheaper unlicensed drug, 3,4-diaminopyridine (8, 9). Although BioMarin then voluntarily cut its prices for Firdapse by 10%, the UK commissioners network did not recommend funding of the drug (8). The UK commissioners network took the view that although legally Firdapse and 3,4 diaminopyridine were two separate clinical entities, the two forms of the drug could be considered to be bioequivalent (7). It was calculated that on average, the base form of the drug costs 1200 per patient per annum, whereas Firdapse costs, on average, 44,000 per patient per annum (7). This development apparently led to some prescriptions of the unlicensed 3,4 diaminopyridine (base form), which could be legally challenged by the UK's Medicines and Healthcare Products Regulatory Agency (MHRA) or Biomarin (8). However, as the lead author of the BMJ letter pointed out, such a legal challenge might prove embarrassing for these organisations (8).

So what's next now?

Despite the controversy concerning certain high-cost orphan drugs, at present, these treatments only account for a small percentage of the overall European drug budgets. In 2007, orphan drugs accounted for 1.7% of the French drug budget, 2.1% in Germany, 1.0% in the UK, 1.5% in Italy and 2.0% in Spain (3). However, healthcare systems need to be designed to cope with future demand, and given that most rare diseases are not well treated, there is a likelihood that countries will be asked to fund additional orphan drugs in the future. One study suggested that there will be between eight and 12 new orphan drugs approved in Europe each year (10). With patients wanting access to these treatments but companies seeking to maximize revenues, European governments are now placed in a difficult situation of over pricing. Although there has been speculation that governments will take a tough line with the industry, it remains to be seen what form such action will take and whether they will remove some of the specific market incentives that were designed to stimulate orphan drug R&D in the first place (11). A delicate balance will need to be struck so as not to reverse the advances made in orphan-drug development and treatment access.


1. European Commission website, "Rare Diseases,", accessed 1 July 2013.

2. European Medicines Agency website, "28 February 2013—Rare Disease Day: Rare disorders without borders,", accessed 1 July 2013.

3. W. Hughes-Wilson et al., Orphanet Journal of Rare Diseases 7 (74) (2012), accessed 1 July 2013.

4. European Organisation for Rare Diseases (EURORDIS) website,, accessed 1 July 2013.

5. K. MacDonald, BBC, "Orphan drugs: Remarkable drugs at remarkable prices," Press Release, 16 Jan. 2013.

6. BBC website, "A GP's view: Orphan drug costs prohibitive,", accessed 1 July 2013.

7. West Midlands Commissioning Policy (WM/35),, accessed 1 July 2013.

8. D. Nicholl, British Medical Journal website, "It's the BMJ wot won it, and the NHS should think like Tesco,", accessed 1 July 2013.

9. V. MacDonald, Channel 4 News, "Drug companies exploiting law for profit,", accessed 1 July 2013.

10. European Organisation for Rare Diseases (EURORDIS) website, "Orphan drugs: rising to the challenge to ensure a better future for 30 million patients in Europe,", accessed 1 July 2013.

11. S. Bennet, Bloomberg Businessweek, "Orphan drugs could lose their government subsidies," Press Release 11 Apr. 2013.


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