The defendant clinical commissioning groups (“CCG”s) adopted a policy on the treatment of age-related macular degeneration which referred to three different drugs for treating patients with the neovascular form of that condition, known as “wet AMD”. In patients suffering from the condition, loss of vision was caused by the abnormal growth of new blood vessels beneath the macula of the retina, stimulated by a protein known as vascular endothelial growth factor (“VEGF”). Each of the three products referred to in the policy was an “anti-VEGF” product which inhibited VEGF when injected into the eye. The first two products were marketed by the first and second claimants respectively and each held a marketing authorisation for opthalmic use, under Parliament and Council Directive 2001/83/EC, issued by the European Commission on the recommendation of the European Medicines Agency. The defendants’ policy indicated that the third product, Avastin, would be offered to certain patients with wet AMD as the preferred treatment option, being considerably cheaper than the other two products. The marketing authorisation for Avastin was for the treatment of cancer, but clinical trials showed that, when used “off-label” for the treatment of wet AMD by injection into the eye, there was no clinically significant difference between Avastin and other anti-VEGF products in terms of safety or effectiveness. When used to treat wet AMD, Avastin was generally “compounded” by dividing up the vials supplied by the manufacturer into smaller doses which were then usually placed into plastic syringes. Guidance issued in August 2011 by the Medicines and Healthcare products Regulatory Agency, an executive body of the Department of Health, advised that such use, involving manipulation of the medicine to produce multiple doses, resulted in an “unlicensed medicine”. The claimants sought judicial review of the policy on the grounds, inter alia, that there was no lawful basis for the supply of Avastin to treat wet AMD and that the policy fundamentally undermined the objective of Directive 2001/83 and was contrary to the duty of sincere co-operation in article 4(3)EU of the EU Treaty, being liable to jeopardise patient safety and to damage and undermine the coherence of the European Union regime including the protection afforded to pharmaceutical companies in relation to their products. The judge dismissed the claims.

On the claimants’ appeal—