The High Court in London has refused to grant drugmakers Bayer and Novartis’ request for a judicial review of a decision by 12 NHS clinical commissioning groups (CCGs) in the north of England to offer Roche’s Avastin as a preferred treatment option for a degenerative sight condition, rather than their more expensive alternatives.
The 49-page decision, handed down by Mrs Justice Philippa Whipple on 21 September, rejected as “absurd” claims by Bayer and Novartis that there was no legal basis for supplying Avastin to treat the condition and that the CCGs’ shared policy flouted EU Directive 2001/83 on medicinal products for human use.
Avastin belongs to a class of drugs used to treat the abnormal growth of new blood vessels, known as vascular endothelial growth factor (VEGF) inhibitors, and was first granted a marketing authorisation by the European Medicines Agency (EMA) for the treatment of colorectal cancer in January 2005. While it was subsequently approved for other oncology uses, Roche has never applied for marketing authorisation for the ophthalmic use of Avastin and the drug has never been approved for these purposes.
Nevertheless, Avastin has been shown to be effective as a treatment for a variant of age-related macular degeneration, known as “wet AMD”, which causes abnormal blood vessels to develop inside the eye and in more than half of cases leads to visual impairment or blindness within three years. In December 2014, the Royal College of Ophthalmologists (RCO) said on the basis of two clinical trials that there was “no clinically significant difference” in ill effects arising from Avastin and Lucentis, another Roche-owned VEGF inhibitor, which has been marketed in Europe by Novartis since 2007.
There are, however, significant differences in the costs of the two drugs: with Avastin costing £28 per injection compared to Lucentis’s £551. Bayer’s VEGF inhibitor, Eylea, which was granted marketing authorisation for ophthalmic use in November 2012, costs £816 per shot.
In 2015, 120 CCGs – the successor organisations to English primary care trusts, responsible for planning and commissioning of health care services for their local area – wrote to then-Health Secretary Jeremy Hunt saying Lucentis had become the “default option” for wet AMD treatment and asked him to take “urgent action” to facilitate the use of Avastin to save money. Hunt replied that European and English law blocked companies from making and selling unlicensed products but noted that the UK’s National Institute for Health and Care Excellence (NICE) was working on a clinical guidance that would refer to Avastin as well as Lucentis when discussing treatments for wet AMD.
Between July and September last year, based in part on the same clinical trials as the RCO mentioned in its report, 12 CCGs in the north east and Cumbria adopted a shared policy whereby Avastin would be offered to all new patients receiving treatment for wet AMD and all existing patients using Lucentis and Eylea, giving them the option to choose which drug they receive.
In November, Bayer and Novartis made their application for judicial review, claiming the shared policy was based on the CCG’s inaccurate belief that there was a lawful basis for supplying Avastin as a wet AMD treatment. They also claimed the policy undermined the objectives of Directive 2001/83, in particular its stipulation that drugs can’t go to market without a marketing authorisation issued by a competent authority in a member state.
The companies argued, based on Directive 2001/83, that the EMA had exclusive competence to determine the safety and efficacy of ophthalmic drugs in the EU, whereas national authorities (such as NICE) had competence to measure the degree of benefit to patients. The CCGs claimed that this was a misreading of the Directive, arguing that national authorities and the CCGs themselves were competent to assess Avastin’s effectiveness as a wet AMD treatment, taking into account safety and cost.
Whipple J said the EMA’s role was both established and limited by the directive. While the EMA and the national regulatory agencies of member states had sole competence to decide whether a medicine should be granted a marketing authorisation, they are not empowered to conduct a wider enquiry into the medicine’s efficacy in treating other conditions, including comparing it to other medicines that are available for the same use.
The fact that Roche hadn’t applied for a marketing authorisation for the use of Avastin to treat wet AMD demonstrated “the limits of the EMA’s role,” Whipple J said. “The EMA is simply not involved in the wider consideration of Avastin for ophthalmic use; nor could it be, unless and until Roche asks it to be.”
The effect of this wasn’t, as Bayer and Novartis claimed, that national healthcare authorities were barred from considering Avastin as a wet AMD treatment. “That seems to me to be an absurd proposition,” the judge said; one that would give “unbounded power” to pharmaceutical companies to decide which medicines were made available for which purpose and would be “seriously detrimental” to maintaining a cost-effective health system.
Cost, moreover, is a lawful ground on which doctors can base the prescription of a drug, the judge said.
Bayer and Novartis had claimed that it was impermissible for a doctor to prescribe an unlicensed drug just because it was cheaper than its licensed alternative, citing the General Medical Council's (GMC) “good medical practice” guidance which holds that there must be “medical reasons” for making such a prescription.
The CCGs argued the companies had misread the relevant sections of the GMC guidance, which state what doctors “should usually” do, and don’t bind them by statute. The CCGs further noted that the “medical reasons” exception was just one example of a situation whereby an unlicensed treatment would be favoured and that the “unusual” nature of the current case might well admit other exceptions. Clinicians are also entreated, more than once, in the guidance to effectively manage their resources, the CCGs pointed out.
Whipple J agreed with the CCGs, finding that the guidance didn’t explicitly preclude the prescription on unlicensed medicines where there were licensed alternatives available and didn’t provide a comprehensive list of scenarios in which such a course of action would be appropriate. Moreover, the guidance “considered overall, positively requires treating clinicians to take cost into account as an element of good medical practice,” she said.
Bayer and Novartis had exaggerated the reach of Directive 2001/83 in a way that pushed their submissions “over the line which separates the EU's competence from that which is reserved to Member States,” Whipple J said. A doctor might be found to have behaved inappropriately in prescribing an unlicensed drug and may face proceedings before his or her professional regulator, the judge added, but professional misconduct isn’t the same as unlawfulness and a breach of professional guidance can’t be equated with a breach of the law.
The RCO on Friday welcomed the judgment as a “vindication” of its campaign in favour of Avastin as a wet AMD treatment, saying it offered doctors assurance that they could offer the best treatment for their patients’ needs.
“Wet AMD is the biggest cause of vision loss in the UK and the hospital eye service is dealing with over 40,000 new diagnoses of wet AMD annually,” the college said. “It has been estimated that an adoption of Avastin, as part of a choice of drugs routinely prescribed for treatment, would release around £500million per year back to the NHS.”
The companies have until 12 October to apply for permission to appeal the decision; their counsel declined to comment on the likelihood of further proceedings when asked by PLN
In the England and Wales High Court
Bayer Plc v NHS Darlington Clinical Commissioning Groups (CCG) & Ors
- Judge Phillipa Whipple
Counsel to Bayer
- Arnold & Porter
Jemima Stratford QC and Emily MacKenzie of Brick Court Chambers
Counsel to Novartis
- Covington & Burling
Tom de la Mare QC and Eesvan Krishnan at Blackstone Chambers
Counsel to the CCGs
- Mills & Reeve
David Lock QC and David Blundell at Landmark Chambers
Counsel to Roche
Partner Sarah Ellson and association Holly Bontoft
Martin Chamberlain QC at Brick Court Chambers