[Ip-health] Neurologists and paediatricians call for action on “massive” rises in the prices of orphan drugs

James Love james.love at keionline.org
Wed Dec 29 07:22:25 PST 2010


BMJ 2010; 341:c6466 doi: 10.1136/bmj.c6466 (Published 16 November 2010)
Cite this as: BMJ 2010; 341:c6466


Orphan Drugs

Open letter to prime minister David Cameron and health secretary Andrew

Neurologists and paediatricians call for action on “massive” rises in
the prices of orphan drugs

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

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.

See Editorial, doi: 10.1136/bmj.c6456; Feature, doi:10.1136/bmj.c6459;
Analysis, doi:10.1136/bmj.c6471.


Martin, D. Hospitals are forced to use unlicensed drugs to save
millions. Daily Mail 27 Sep 2010.

Boseley S. EU loophole sends drug prices soaring. Guardian 24 Jun 2002.

Leonard JV, Richmond S. Pricing of orphan drugs. Lancet2009;373:462.
[Medline][Web of Science]

Signed by: 
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 david.nicholl at nhs.net

James Love, Director, Knowledge Ecology International
http://www.keionline.org | http://www.twitter.com/jamie_love
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