- David J Nicholl, consultant neurologist, City Hospital, Birmingham,
- David Hilton-Jones, consultant neurologist, John Radcliffe Infirmary, Oxford,
- Jacqueline Palace,, consultant neurologist, John Radcliffe Infirmary,
- Sam Richmond, consultant paediatrician, Sunderland Royal Hospital, Sunderland,
- Sarah Finlayson, congenital myasthenia clinical fellow, John Radcliffe Infirmary,
- John Winer, consultant neurologist, University Hospital Birmingham,
- Andrew Weir, consultant neurologist, Royal Berkshire NHS Trust, Reading,
- Paul Maddison, consultant neurologist, Nottingham University Hospitals NHS Trust, Nottingham,
- Nick Fletcher, consultant neurologist, Walton Centre for Neurology & Neurosurgery, Liverpool,
- Jon Sussman, consultant neurologist, Greater Manchester Neuroscience Centre, Hope Hospital, Salford,
- Nick Silver, consultant neurologist, Walton Centre for Neurology & Neurosurgery,
- John Nixon, consultant neurologist, Royal Preston Hospital, Preston,
- Dimitri Kullmann, consultant neurologist, Institute of Neurology, London,
- Nick Embleton, consultant paediatrician, Royal Victoria Infirmary, Newcastle upon Tyne,
- David Beeson, professor in neuroscience, Weatherall Institute of Molecular Medicine, Oxford,
- Maria Elena Farrugia, consultant neurologist, Institute of Neurological Sciences, Southern General Hospital, Glasgow,
- Marguerite Hill, consultant neurologist and senior clinical tutor, Abertawe Bro Morgannwg University Local Health Board, Swansea,
- Chris McDermott, consultant neurologist, Royal Hallamshire Hospital, Sheffield,
- Gareth Llewelyn, consultant neurologist, Royal Gwent Hospital, Newport,
- James Leonard, professor emeritus, Institute of Child Health, University College London,
- Michael Morris, chairman of the Myasthenia Gravis Association, Derby
- Correspondence to: D J Nicholl
We are writing to you as a group of clinicians treating patients with so called “orphan” diseases (and one representative of a patients’ group) to express our concern at an unintended effect of the European Union’s regulations on orphan drugs. The original purpose of this legislation, passed in 1999, was to encourage drug companies to conduct research into rare diseases and develop novel treatments. However, as the rules are currently enacted, many drug companies merely address their efforts to licensing drugs that are already available rather than developing new treatments. Once a company has obtained a licence, the legislation then gives the company sole rights to supply the drug. This in turn allows the company to set an exorbitant price for this supply and effectively to bar previous suppliers of the unlicensed preparation from further production and distribution.
We believe that this behaviour is not in the best interests of patients or the NHS but is undoubtedly significantly advantageous to drug companies. We have made representations to the Department of Health for England and the UK Medicines and Healthcare Products Regulatory Agency. In reply we have simply been quoted the rules, and no one seems willing to investigate the issues we are raising or to consider whether the system should be changed. We are asking you to identify the appropriate individuals who can act on this unacceptable situation.
One example of the effect of these rules is the drug 3,4-diaminopyridine (3,4-DAP). We have been using 3,4-DAP for more than 20 years to treat two rare diseases, Lambert-Eaton myasthenic syndrome and congenital myasthenic syndrome; both cause disabling muscle weakness of the limbs, body, eyes, and face, together with swallowing and breathing problems, which can be fatal. The drug improves muscle strength and is used either because other treatments haven’t worked well enough or to avoid using drugs that can have serious side effects. Expert clinicians take the responsibility for informing patients about the drug and prescribing it. It has an excellent safety record. Until now 3,4-DAP has been produced by a small drug company on an unlicensed basis and costs between £800 (€945; $1285) and £1000 per patient per year.
The company BioMarin has now been issued with a licence to supply the drug (marketed as Firdapse) throughout Europe and has priced its product at £40 000 to £70 000 per patient per year—a 50-fold to 70-fold increase. BioMarin merely had to demonstrate that its drug works, using data generated from the unlicensed version. It has simply produced a slightly modified version (amifampridine) that meets regulatory standards and has been allowed to set the price at an exorbitant level with no clinically relevant advantage.
This high cost means firstly that some funders (primary care trusts) have refused to pay for the drug, because it doesn’t fulfil cost effectiveness criteria. It also means that, where it is funded, no additional funding source has been identified, which must mean that patients in other areas are being deprived of NHS funding. The cost to the NHS is likely to be above £10m a year.
We urge you to instruct urgent review not only for the sake of our particular patients but also for the many other patients who are likely to be affected in the near future as other drug companies take advantage of this loophole. Extraordinarily, there is a website that lists other drugs that can be similarly exploited (www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/HowtoapplyforOrphanProductDesignation/ucm216147.htm).
In the present economic situation it seems vital to ensure that systems are in place to prevent excessive commercial profits being made at the expense of patients and public spending. Although the pricing of 3,4-DAP is the most recent example of this trend,1 massive price rises have been noted in treatments for other orphan diseases for years; examples include N-carbamylglutamate (for N-acetylglutamate synthetase deficiency), sodium phenylbutyrate (for ornithine carbomoyltransferase deficiency), ibuprofen and indometacin (for patent ductus arteriosus), caffeine citrate (for apnoea in preterm infants), and even nitric oxide (for pulmonary hypertension).2 3
We believe there to be sufficient grounds for the UK parliamentary health select committee to look at the pricing of orphan drugs, as the costs directly affect patients of all ages with a diverse range of conditions across the country. If an investigation were to find evidence of artificially high pricing, the Office of Fair Trading should consider pursuing the issue.
Legislation on orphan drugs, far from encouraging the development of new treatments for orphan diseases, is severely limiting the availability of existing treatments. We believe that the Medicines and Healthcare Products Regulatory Agency and Department of Health should not just state the rules but should act now to progress the issue of unfairness upwards, so as to instigate change.
Cite this as: BMJ 2010;341:c6466
Competing interests: All authors have completed the unified competing interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare no support from any organisation for the submitted work; JL has acted as a consultant to orphan drug manufacturers (Special Products Ltd and Swedish Orphan), has been paid travel expenses to attend professional meetings on orphan drugs, was on an educational advisory panel for the Orphan Academy, supported by Orphan Europe, and has chaired workshops for Swedish Orphan; and no other relationships or activities that could appear to have influenced the submitted work.