David Lock: Avastin and Lucentis—It’s time for NHS commissioners to act rationally by limiting the choices for wet AMD patients

The news that a Cochrane Review has concluded that Avastin (bevacizumab) is as safe as Lucentis (ranibizumab) to treat patients with wet age related macular degeneration (“wet AMD”), along with other studies that have shown the two drugs have broadly the same level of clinical effectiveness, comes as no surprise to those of us who have been involved in this debate for a number of years.

Lucentis is a “licensed” drug for wet AMD, whereas Avastin is not licensed for this condition. But Avastin is not an unlicensed drug per se; it is just licensed for a different condition, namely treating patients with certain cancers. The beneficial use of the drug for wet AMD patients seems an unintended and highly cost effective benefit. There is nothing unlawful in clinicians using an unlicensed drug to treat NHS patients, as paediatricians know because they use unlicensed drugs all the time. So why should the NHS keep paying out for a drug that is 10 times more expensive than an equally safe and clinically effective alternative?

The answer to that question will depend on whether NHS policy makers have the courage to take on vested pharmaceutical interests by adopting policies to use the cheaper but equally clinically effective drug. There are some who say that it would be “unlawful” to do so, but the source of this claimed unlawfulness is far from clear—if there is any unlawfulness at all. In contrast, the savings if Avastin was to be used routinely in the NHS would run into hundreds of millions, and that money could be recycled into other treatments that are presently not funded.

It might seem strange to some that Avastin is not licensed to treat wet AMD when there is a substantial body of clinical data which supports its effective use as a medicine for that illness. Why does the pharmaceutical company that owns this drug not cash in on this potential market? The answer is complex, but may in part lie with the fact that the ultimate intellectual property rights holder for both Avastin and Lucentis is (or at least was a few years ago) the same company, namely Roche. Novartis have the European rights from Roche to market Lucentis, but the IP rights for both drugs are ultimately owned by Roche.

It may adversely affect the value of Roche’s IP rights in Lucentis if Avastin was licensed—at a tenth of the price of Lucentis—to treat wet AMD. It would also cost Roche hundreds of millions of dollars to do the clinical trials to satisfy regulators to grant a licence for Avastin. From the outside, therefore, it seems to make perfect commercial sense for Roche not to apply for a licence for Avastin to be used to treat wet AMD patients. It amounts to asking Roche to sacrifice their profits for the sake of more cost effective treatment for patients. In the end, Roche are responsible and accountable to their shareholders, so that is never going to happen.

Others see this conundrum differently. Italy’s antitrust regulator has fined Novartis and Roche Holding AG around €180m (£150m; $251m) for allegedly colluding to prevent the use of Roche’s Avastin cancer drug as a treatment for an eye disease. That seems a bit rough when they are only doing what one would expect commercial companies to do.

It may also not be irrelevant that the public position of both companies is that Lucentis is a better treatment for wet AMD than Avastin. That is a clinical judgment which conveniently fits their commercial interests and so, to misquote Mandy Rice-Davies, “they would say that, wouldn’t they.” But it is hard to see why Roche should pay a large amount of money to put Avastin through clinical trials when the effect will be to devalue the value of its interest in Lucentis. Only time will tell whether the Italian fine will stick—but I suspect years of litigation ahead because the rights and wrongs on the market abuse issue are far from clear.

However, the judgment as to which is the better drug for patients (i.e. more clinically effective and cost effective for patients) is ultimately for clinicians and not for drug companies. The drug companies produce pharmaceutical products, but it is NHS commissioners and doctors—not the drug companies—that decide which drugs should be purchased and which should be used for patients.

The drug licensing system is, of course, about the commercial marketing of drugs and not about clinical use. However, clinicians are naturally worried that if they have a choice about using a licensed or an unlicensed drug, they will be hauled before the GMC if they elect to use an unlicensed drug. The recent GMC guidance favouring licensed drugs over unlicensed drugs was not the GMC’s finest hour. It was an example of the GMC bowing to pharmaceutical and governmental pressure, which was more aimed at the health of the British pharmaceutical industry than the health of NHS patients. That is my view and others have different views.

Now that it seems fairly clear that scare stories about Avastin’s use for wet AMD have all the credibility of a chocolate teapot, the NHS has some choices to make. In 2012 the former health minister, Mike O’Brien QC, made his position clear. He said: “The health secretary should condemn what Novartis is doing. Andrew Lansley should refuse to allow the NHS to be bullied by Novartis. The interests of the patient and the NHS must come first.” That statement was issued when Novartis attempted to use a judicial review to stop an NHS body favouring Avastin over Lucentis.

The action was settled before it came to a final trial and so the case was not a precedent for anything.* But the threat of legal action to stop NHS commissioners doing the right thing in this area remains. However, it is just that—a threat. No case has ever (as far as I am aware) resulted in a court judgment which says an NHS commissioner should use drug A rather than drug B.

Now that this new Cochrane evidence is available, perhaps it is the time when NHS bodies should ask themselves whether they should continue to use an expensive drug when a much cheaper one is both available and is of proven clinical effectiveness and safety? One thing seems to me to be clear. If commissioners and NHS trusts continue to give clinicians the choice, no clinician who does not want to end up before the GMC will choose the unlicensed drug. But if drug A is far more cost effective than drug B, why should an NHS under vast financial pressure give clinicians the choice to use a less cost effective drug?

So what should commissioners do? The answer seems simple—have courage and remove the choice. If NHS commissioners decide that they will only commission the provision of Avastin for wet AMD patients (save in exceptional circumstances where approved by an individual funding request panel), doctors and patients know where they stand and doctors are as fully protected as they could be from GMC action.

If NHS commissioners took this position, it would be Avastin or nothing for a wet AMD patient under the NHS, and the money freed up would deliver vastly more NHS treatment for so many others. It seems highly unlikely that a doctor would be brought before the GMC for treating a patient who did not elect to buy Lucentis privately.

Will Novartis seek to challenge the commissioners in a judicial review? It is a possibility, but a judicial review claimant has to make full and fair disclosure of all relevant material. Given everything that is happening in Italy, the disclosure requirements might make that a fairly difficult judgment call. However, article 167 of the Treaty for the Functioning of the European Union says that the way that EU member states organise their healthcare systems is outside EU law. It is therefore hard to see how a decision by an NHS body about whether to commission one drug or another could be challenged on the basis of an alleged breach of EU law. It is an area where the EU has no “competence.”

Removing the choice from clinicians between Avastin and Lucentis for routine wet AMD cases seems to be the right policy decision to promote cost effective medical treatment for NHS patients. However, the difficult question will be how many NHS commissioners have been down the yellow brick road to collect their portion of the lion’s courage and will do so.

*I was instructed as counsel for the NHS bodies.

David Lock is a barrister and QC, Landmark Chambers. He is a board member of Brook Sexual Health, a member of the BMA Ethics Committee, and chairs Innovation Birmingham which runs the Science Park in Birmingham. He has set up a website www.gplaw.co.uk, which pulls together law, guidance, and practice that affect general practitioners.

Competing interests: I am a member of the Labour Party and am a non-executive board member of Heart of England NHS Foundation Trust. My wife is a doctor who is employed by Redditch and Bromsgrove Clinical Commissioning Group. In the past I have given legal advice to NHS bodies on the issue discussed in this blog and may do so if required in future.

  • CitizenofEU

    For the FR gov, Mathias Ask published an article (Drug Companies Oppose Moves to Reimburse Off-Label Medicine) in BMJ. For the German approach, see Judgment of the European Court of Justice in Novartis case C-535/11 of April 2013

  • Pete Husky

    Whilst the overriding point is correct, the key tension that commissioners face is that NICE has issued a technical appraisal directing the use of Lucentis, rather than allowing for both drugs. Rather than the GMC, the question that opponents of the more effective drug cite is provider contract compliance with Nice TAs as assessed by the CQC, and the duty of commissioners to implement TAs.
    …Which leads appropriately to the more fundamental question of why NICE’s remit cannot extend to considering drugs other than those put forward by the manufacturer for a given condition. The brave decisions of commissioners need to take place under the shadow of a savvy health technology appraisal body.