Are the odds shifting against pharma in the fight for cheaper treatment for macular degeneration?
BMJ 2017; 359 doi: https://doi.org/10.1136/bmj.j5016 (Published 01 November 2017) Cite this as: BMJ 2017;359:j5016
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The term "licensed medication" is pejorative. It would be better to use the term "marketing authorisation" as this is a more accurate description of the status of the medication as it encompases the commercial element of the definition.
Competing interests: No competing interests
Although I fully understand that the GMC must uphold European law, the GMC’s interpretation of the law appears to be misinformed.
‘Good practice in prescribing and managing medicines and devices’ (GMC 2013) is an important guideline relating specifically to the individual prescriber and the individual needs of the individual patient.
The much quoted European court case in 2012 that the GMC (and others) refer to concerns the importation of similar products without market authorisation to an EU country (Poland). It does not relate to the legal role of the individual prescriber.
The importance of distinguishing the regulation of medicinal products from their use in medical practice is emphasised in the recent European Union report ‘Study on off-label use of medicinal products in the European Union’ (February 2017), which states: ‘’EU legislation does not regulate the way medicinal products are ultimately used in medical practice. The prescribing of a medicinal product, on-label or off-label, is a decision taken within the relationship between a patient and his or her treating healthcare professional (HCP)’’.
Furthermore, in June 2015 The European Court of Justice indeed confirmed that “off-label prescribing is not prohibited, or even regulated, by EU law” and that “There is no provision which prevents doctors from prescribing a medicinal product for therapeutic indications other than those for which a marketing authorisation has been granted.” (T-452/14 Laboratoires CTRS v Commission, paragraph 79).
Any interference in the individual doctor prescribing an off-label drug for an individual patient by threat of legal action by a pharmaceutical company may be considered by the CMA as an abuse of a dominant market position in breach of the 1998 Competition Act.
Although 'Innovation Health an Wealth' (2012) required Primary Care Organisations to make all NICE TA recommended drugs available , this did not mean that clinicians had to prescribe,. unless they chose to do so.
There appears therefore no restriction in ophthalmologists choosing to use bevacizumab (Avastin) in wet AMD other than the restriction imposed by the GMC based upon questionable legal interpretation.
In August 2017, I wrote to the GMC and am currently awaiting a further response.
Competing interests: No competing interests
For individuals whose vision is impaired by wet Adult onset Macular Degeneration (AMD), the fact that progression of this relatively uncommon disease can be controlled, by suppressing vascular endothelial growth factor (VEGF) with the intravitreal injection of a monoclonal antibody(mab), is a triumph of the costly research undertaken by Pharma.
Of the 3 mabs that are effective against VEGF, now that non-inferiority of treatment outcomes are known, the fact that 2 are manufactured by the same pharmaceutical company (Roche/Novartis) gives rise to the unique circumstance because of the extreme price differential, not seen elsewhere. It is not in the commercial interests of Roche/Novartis to seek a marketing authorisation (MA) that would allow them to promote the cheaper agent. Current European law, which exists to protect the public from inferior imports & to support the production of high-quality products by Pharma stipulates, that when a Medicine that is licensed for a particular indication exists, cost is not an adequate reason for a Medicine that lacks a MA to be prescribed. The GMC & NICE cannot be expected to recommended practice that can be challenged in Law.
The only way to rectify this unique circumstance in favour of cost-effectiveness is to enact new UK legislation, wherein the Government establishes a statute defining that bevacizumab prepared for intravitreal injection is classed as a "unique special". Existing EU law relating to Orphan Medicines provides a template: http://eur-lex.europa.eu/legal-content/EN/AUTO/?uri=celex:32000R0141
Asher Mullard, Contributing Editor for Nature Reviews Drug Discovery, in the June 2012 issue (doi:10.1038/nrd3749) revealed that the original EU patent of bevacizumab expires in April 2018. Roche/Novartis will no doubt seek an extension, so legal arguments will take place as Brexit eats away at the all-encompassing EU scheme for patents that was to be based in London ( along with the European Medicines Agency). In short, the UK could decide to manufacture bevacizumab for its own use in AMD & in other eye conditions such as diabetic macular oedema (DMO).
The UK Medicines & Healthcare Products Regulatory Agency (MHRA) licences the pharmacies at the Royal Liverpool University Hospital & the Broadgreen Hospital to manufacture aseptically prepared specials, & bevacizumab is currently aliquoted here, at the request of individual clinicians, for the treatment of rubeotic glaucoma by intravitreal injection.
The MHRA also licenses other larger facilities that could produce greater volumes.
In a survey of its members, carried out by the Macular Society in 2012 (personal communication from Cathy Jelf, CEO): 37% of respondents agreed that NHS cost-savings would lead them to have bevacizumab instead of expensive ranibizumab.
I hope that this debate does get the wider airing among the public that it deserves.
Although the existence of personal health budgets (PHBs) for chronic conditions is largely unknown to NHS service-users. (A PHB is an amount of money to support the identified healthcare and wellbeing needs of an individual, which is planned and agreed between the individual, or their representative, and the local clinical commissioning group (CCG). It isn’t new money, but a different way of spending health funding to meet the needs of an individual.) These considerations should perhaps be applied to the chronic eye condition that is AMD, and then the views of the individual be taken into account. By choosing the less-expensive anti-VEGF agent, the unused sum could be directed to support other sight-preserving services or aids fitted to their home.
So there you have it - just amend the Medicines Act to make right this affront to the best use of NHS funds. I just hope that it doesn't cost £84M in legal fees - anyone for a Private Members Bill?
Competing interests: No competing interests
It is of course ludicrous that the NHS is forced to use very expensive medicines when a much cheaper, equally effective and equally safe alternative exists. It is also understandable why for commercial reasons Roche do not apply for a licence for the use of Bevacizumab in the eye.
The NHS cannot afford to waste money so I propose that parliament legislate that the Department of Health can also apply to license a medicine, naturally under the same procedure that a firm has to follow. Once it had this power it could effectively bring very strong pressure on any firm to negotiate reasonable prices for any alternative, or apply for the licence themselves for the inexpensive alternative.
Competing interests: No competing interests
Re: Are the odds shifting against pharma in the fight for cheaper treatment for macular degeneration?
For several years the treatment option in AMD or age related macular degeneration, was anti-oxidants with varying protocols. With the implication of VEGF in neovascularisation, Avastin has been used as a treatment option from as wide a diagnosis as diabetic retinopathy to AMD with its choroidal neovascularisation (CNV). Laser photocoagulation has been used for treatment of neovascularisation. Verteporfin and photodynamic therapy is another treatment protocol in AMD. There are few comparative studies on varying efficacy of the above treatment protocols.
Pharma giants, all of them offering the same product, a monoclonal antibody, for treatment of AMD and also in same breathe a very varied diagnosis as carcinoma's, requires some thought.
Few clinicians vouch for the efficacy of the drug as an intravitreal, whether from vested interests or a genuine study is a matter of debate. However it would aid everyone concerned, mechanistic action of monoclonal antibody in age related macular degeneration which is so benign to use of the same in carcinomas.
We have used antioxidant based treatment protocol and laser photocoagulation as treatment option.
Competing interests: No competing interests