In September 2018, in the case of Bayer and Novartis Pharmaceuticals v NHS Darlington CCG and others, a group of CCGs from the North East of England successfully defended a challenge to the lawfulness of their policy to give the drug Avastin preferred status for the treatment of wet age-related macular degeneration (Wet AMD), potentially saving the NHS millions of pounds.
The crux of the claimants' case was that the Court should assess the lawfulness of the CCGs' policy on the basis that what it envisages and intends is a large-scale commercial supply of an unlicensed drug.
The claimants, Bayer and Novartis, market the rival treatments of Eylea and Lucentis which are significantly more expensive that Avastin. It is relevant that Eylea and Lucentis are licensed for the treatment of Wet AMD, whereas Avastin (although a similar drug) is licensed for the treatment of a number of different cancers. When used for ophthalmic treatment, Avastin is usually compounded and referred to as 'compounded bevacizumab' ("CB").
A marketing authorisation for using Avastin in connection with Wet AMD has never been sought by its owners (Roche), notwithstanding that numerous studies have demonstrated Avastin to be as safe and effective for the treatment of Wet AMD as its rival drugs, and the use of Avastin for Wet AMD is widespread in a number of countries including Germany, Italy, the United States and the UK. Further, after the claim had been issued, NICE issued guidance supporting the view that there is no material difference between Avastin, Lucentis and Eylea in patient safety terms.
The claimant opposed the policy on four grounds: (1) they said that the supply of Avastin to treat Wet AMD was unlawful under EU law because it does not have a marketing authorisation for ophthalmic use; (2) the use of Avastin for ophthalmic use undermines drug regulation; (3) it undermined patients’ rights of access to NICE approved drugs; and (4) the patient information sheet accompanying the policy was misleading and inaccurate.
The Court considered that the challenge turned on a handful of issues in respect of which it reached the following conclusions:
- Contrary to the claimants' case, the European Medicines Agency (which considers applications for marketing authorisations) does not have exclusive competence to determine whether Avastin is clinically effective and safe for ophthalmic use. NICE and the CCGs also have competence in that arena.In reaching this conclusion, the Court noted that it would be an absurd proposition to conclude otherwise, as "[i]t would give unbounded power to the pharmaceutical companies to decide which medicines to make available for which purpose" which is not what is envisaged by EU law. Such a position would be seriously detrimental to the wider public interest in maintaining a cost-effective public health system.
- Treating clinicians can lawfully choose Avastin for ophthalmic use on grounds of cost.
- The claimants' argument that Avastin is unsafe when used for ophthalmic purposes did not arise for determination, but the court noted that NICE has concluded that Avastin so used is safe and there is no material difference between Avastin, Eylea and Lucentis in patient safety.
- Whilst the Medicines and Healthcare products Regulatory Agency (MHRA) 2011 guidance concludes that CB is an unlicensed medicine (i.e. without a marketing authorisation) rather than an off-label use of a licensed medicine (i.e. a medicine being used beyond the terms of its licence), in two EU cases the Court of Justice of the European Union has accepted the description of CB as 'off-label'. The distinction between unlicensed and off-label use appears to depend on a judgement as to the extent of any modification. However, given the findings of the CJEU and the widespread use of CB in the treatment of Wet AMD, the Court invited the MHRA to review its guidance that CB was an unlicensed medicine and noted that the 2011 guidance, which reflects the current MHRA position, was highly unsatisfactory.
- The relevant test in domestic law by which the lawfulness of the CCGs' policy is to be judged is whether the policy is realistically capable of lawful implementation by the NHS Trusts in a way which does not lead to, permit or encourage unlawful acts.
Implementation of the policy
In terms of the lawfulness of implementing the policy, the CCGs said that there were four broad ways, or “modes”, in which the CB could be sourced by NHS Trusts and they argued that each mode was lawful. The modes were:
- Original vial use, which involves drawing a small amount of Avastin directly from the vial for injection directly into the eye; the balance of the drug remaining in the vial being discarded;
- Compounded "in-house" by the hospital's own pharmacy;
- Compounded by another NHS hospital (which supplies other NHS hospitals in its area); and
- Compounded by a commercial entity outside of the NHS.
The Court took the view that mode 1, the original vial use, does not involve anything that could be criticised as re-compounding the drug and must therefore (despite the MHRA description) be regarded as off-label and not unlicensed and this approach does not create any UK regulatory issues for the pharmacy. In effect, they would merely supply the vial to the clinician and an appropriate syringe and the clinician would fill the syringe, inject, and discard the vial. As to mode 2, a hospital pharmacy does not require a marketing authorisation to supply CB to clinicians in the same hospital or Trust because the supply is 'in-house' and also the exemption where the dispensing is in response to an individual prescription may apply. Modes 3 and 4 were regarded as potentially lawful, although this would depend on individual facts.
In finding the CCGs' policy to be lawful, the Court dismissed the claimants' challenge on all four grounds:
- Ground 1 failed because the Court found that EU Law does not prohibit the supply of Avastin, whether compounded or not, to NHS Trusts in any one of the four modes. Each mode provides a means by which the policy might realistically be implemented.
- Ground 2 failed because the claimants significantly overstated the protection afforded to them by EU Law; the use of Avastin for ophthalmic use does not undermine drug regulation. Moreover the purpose of the relevant Directive does not extend to protecting the commercial interests of the pharmaceutical companies in cases where the facts are unusual and the jeopardy to the public purse enormous.
- Ground 3 failed because the effect of the policy was not to undermine NICE; the patient could still choose Eylea or Lucentis if that patient's wet AMD is within the parameters specified in the TAGs for those two medicines.
- Ground 4 also failed as the patient information leaflet was still in draft and not yet published and, as such, there was no decision to challenge. In any event, it was a document which belonged to the NHS Trusts and not the CCGs.
Watch this space
Subject to any appeal, this decision opens up the possibility of other CCGs adopting a similar policy and Trusts adopting a lawful mode of being in a position to use CB for the treatment of Wet AMD. Whilst modes 1 and 2 above would constitute lawful ways of sourcing CB by NHS Trusts, going beyond this into commercial supply or cross-NHS supply would be more risky although not out of the question. Please let us know if you require advice in considering the available options to implement any such policy relating to the use of Avastin for Wet AMD.
The full judgment is available to download here: https://www.judiciary.uk/wp-content/uploads/2018/09/bayer-and-novartis-v-nhs-darlington-ccg-judgment.pdf