Trade Wars we have known and loved: Indianapolis v The World

Several weeks ago Canadians woke up to a Globe and Mail article saying that the pharmaceutical company Eli Lilly, who are based in Indianapolis, was suing their Government for $500 million for loss of revenues linked to the loss of patents on two of its drugs – Zyprexa and Strattera.

“The drug giant alleges that the loss of its patents violates Canada’s obligations under international treaties, including NAFTA, which, under that agreement’s controversial Chapter 11 provisions, allows foreign investors from member countries to sue governments for allegedly violating the treaty”.

This led some Canadians to set up a Petition protesting against “this ridiculous NAFTA (North Atlantic Free Trade Agreement) lawsuit”.

Zyprexa

I had been an expert witness for Teva-Novopharm in the case that led to the Zyprexa patent being struck down. So I have some feel for the issues.

Lilly made several stabs at holding on to Zyprexa (olanzapine) and Strattera (atomoxetine) patents and then tried to overturn the rulings of the Canadian High Court. This new gamble then seems like a last gasp at earning money from the Zyprexa and Strattera patents – or perhaps something more.

Lilly’s Notice of Intent to Arbitrate was served in November 2011. The initial complaint was that the Courts had wrongly invalidated the Strattera patent. This appeal was refused. So they then made it clear to the Supreme Court of Canada that they were going to complain about both the Strattera and Zyprexa patents.

The company had first claimed they were $100 million out of pocket for the Strattera patent. In their next complaint this amount increased this to $500 million for both Strattera and Zyprexa. But their leave to appeal was denied.

Lilly’s argument was that Canadian courts have developed a new “promise doctrine”.

When companies apply for a patent they have to attest or promise that the drug will in due course be shown to have certain advantages over other drugs – in addition to being novel there has to be the promise of a distinct benefit. Some form of this wording about patents is found in most countries and was once applied in the United States.

Canadians need to be Brits or Americans

The company engaged in a very energetic lobbying and PR campaign, in both Canada and in Washington DC, trying to convince legislators and others that Canadian patent law is out of step with the laws of the US and the UK. This was an odd claim in that the laws of the US and the UK are not the same as each other and Lilly were not specifying which law Canada had to conform to.

They also argued that Canada was compelled through treaty obligations to “harmonize” its patent laws with those of its “major trading partners”. But in fact no treaty contemplates harmonization of this type – and again are Canadians supposed to harmonize with the US or the UK?

The UK always had employed the concept of the promise of a patent – until the law was revised substantially in 1977. As in Canada patents were held to be invalid if there was a false statement in the patent or if the benefit said to be inherent in the drug was not established.

The Zyprexa patent

In the cases of Stattea and Zyprexa, the Canadian High Court ruled that the patents were invalid because of the lack of benefit. Lilly made assertions that Strattera would work for ADHD and Zyprexa would have marked superiority and a better side effects profile that other known antipsychotics – and especially that it would show a beneficial lipid profile.

The key thing is these benefits have to be established by the filing date. Lets look at Zyprexa. In the first place there is a real question about originality in that Zyprexa was a drug selected unaltered from a molecular group that had already been patented almost ten years before.

As regards the benefit, the company had done a study in dogs in which Zyprexa caused less elevation of lipids compared with another drug that was never marketed. There was no demonstration at the time of filing for the patent that this was likely to hold true in humans. In fact as it turns out, save perhaps for clozapine, there may not be any other drug in medicine that raises cholesterol levels more than Zyprexa.

A trade war within a free trade zone?

Canada has been using the notion of a patent “promise” since 1932. There is nothing new here, and on this score Zyprexa manifestly failed.

The only thing that’s new is the length to which a company, Lilly, has gone to create a debate where there really is nothing to debate – introducing NAFTA. Here the company claims that it is being treated differently in Canada from what it would expect in the US. NAFTA, though, only provides that foreign entities will be treated the same as domestic entities, not that they will be treated the same in Canada as they would in the United States.

What does the company gain from this? Publicity. It may also be part of an effort to shift Canadian legislators to revise Canadian law to suit Lilly. Canadian government trade lawyers are not conversant with patents or intellectual property, so they may not spot how ridiculous Lilly’s claim is. There is deadline by which the company has to proceed to arbitration, so this issue may just hang over Canadians for some time to.

Strattera

Meanwhile back in the UK ranch, the British Journal of Psychiatry came in the post this week encased in a wrapper showing what looks like a confident executive at a boardroom meeting holding the attention of the meeting.

There is a banner headline: “Strattera now licensed to treat Adults with ADHD”.

And a strapline: “With stable control, ADHD gets less attention”.

Strattera is atomoxetine, a norepinephrine reuptake inhibitor. The company made it expecting it to be an antidepressant. After the selective serotonin reuptake inhibitors, we were all going to get the selective norepinephrine reuptake inhibitors. But it wasn’t much good.

They then thought about it as a bladder stabilizer. Norepinephrine reuptake inhibitors like reboxetine and duloxetine cause urinary retention. Duloxetine was another failed antidepressant that came on the market in Europe as a bladder stabilizer before the company tried to reposition it as an antidepressant in the United States.

Then one of Lilly’s staff, John Heiligenstein, who felt he had some memory problems and had been given a diagnosis of ADHD, tried it on himself and said that he found it helpful. Lilly had a new niche to aim at – just at a time when ADHD was a growing market and there were concerns about the addiction risks of  giving drugs like the amphetamines and Ritalin to children.

Strattera was marketed as the non-dependence producing treatment for ADHD and right from the get go the company pushed the idea that many people don’t grow out of ADHD. If you’ve failed at your job, your marriage, your life, it may be because of your silly doctor failed to recognized ADHD. You go and tell him.

The marketing has been so good that even in the UK health boards are setting up senior psychiatrists posts to manage and run adult ADHD clinics at a cost of around $250,000 per year. Who needs a sales force when you have NHS PLC to do the job of selling for you. All this in a country where twenty years ago no adults and a vanishingly small number of children were thought to have ADHD.

From the sequence of events it should be clear, that there was a real likelihood that any decent Court would have thrown out the patent on Strattera. It’s difficult to think of a pair of drugs that by the time they came to market were less original.

The special relationship

Lilly didn’t have a problem in the UK. We can only speculate on why not but reasons such as the company was quite willing to threaten the UK Government that it would pull its operation out of the UK if it lost its patent. This is not a gentlemanly world.

Lilly doesn’t have an operation to pull out of Canada – which may explain something.

The Strattera edition was the last edition of the British Journal of Psychiatry under Peter Tyrer who has been the editor for the past ten years. Having a journal wrapped in an advert like this is a symbol of a period during which the British journal hasn’t had the nerve to ask pharmaceutical companies to make the data of clinical trials available for scrutiny.