The Patent at Any Price: The Fight For Market Exclusivity in Psychiatric Medications

Hidden in a small blurb in the “Corporate Watch” section of this week’s Wall Street Journal was a piece on pharmaceutical maker Eli Lilly and its blockbuster antidepressant medication Cymbalta.

Lilly’s U.S. market exclusivity for the drug was set to expire in June of 2013, according to the patent. Once that exclusivity expires, generics can enter the market. Clearly this is a threat to the money-making potential of the original drug, so drug companies work hard to keep their exclusivity and extend their patents.

It doesn’t  always involve the most ‘above-board’ type of maneuvering.

So Lilly, a company we’ll have to meet again to address its most creative efforts on behalf of Prozac’s exclusivity, worked to extend Cymbalta’s patent.

The process seemed pretty simple–and the ending ironic.

They extended their patent by 6 months by merely studying the drug’s effects on children. In doing so they bought themselves market exclusivity through December 2013.

But what’s odd about this, to me, is that Lilly won’t be seeking approval to market Cymbalta for children because (ready for this?) study results on its efficacy was inconclusive.

So, if I’ve got how this works straight, just by looking at some possible use for a medication, a company earns itself the right to keep generics out. This is true even if the results don’t support the use of the medication in that area of study.

Does something seem awry?

Perhaps you think this situation seems unusually outlandish?

Well, let’s return to Lilly, poised, in 1998, to lose patent on their cash cow drug, Prozac, earning at the time over $2 billion per year.

Here’s the linchpin in patent extensions: If you can find a new use for your drug, you can extend your patent.

So Lilly pulled together researchers, thought long and hard–and came up with a new use for Prozac as a treatment for a disorder almost unheard of up to that point, and one that won’t officially make it into of the Diagnostic and Statistical Manual of Mental Disorders, the mental health ‘Bible,’ appendix until the next publication, in 2013.

Newly listed at the time in the DSM’s appendix as “under evaluation,” premenstrual dysphoric disorder (PMDD) was an unknown quantity in the late 90s, but Lilly pushed hard and funded research to indicate that PMDD was a real and distinct illness, quite separate from PMS, and one that needed antidepressant treatment.

The rest, as they say, is history. The research convinced the FDA to approve Prozac to treat PMDD–and Lilly won a patent extension until 2007.

They repackaged the pill in a lovely lavender, renamed it Sarafem, and actively began marketing it to women.

Launched in the U.S. in August 2000, it already  had sales of $10.0 million for the third quarter of 2000. [See ELI LILLY AND COMPANY REPORT FOR THE QUARTER ENDED SEPTEMBER 30, 2000.]

But there are other ways for companies to maintain exclusivity and keep reaping financial benefits, even without pushing for somewhat suspect (at the time) new uses of a drug.

As high-grossing medications are poised to go off patent, the drive to find those ways becomes even stronger.

Notice that in each year from 2008 to the present, psychiatric drugs are included in the major medications poised to lose patent protection. [See the Wall Street Journal’sBig Pharma Faces Grim Prognosis” for this and other visuals, plus the financial reasons drug companies are willing to fight so hard in this battle.]

In fact, let’s add more to the 2012 poised-to-be-losers, of which the top four are psychiatric medications.

So, quite motivated not to lose protection, pharmaceutical companies become creative.

Why not simply combine two high-grossing meds into one pill?

It seemed that Lilly’s Prozac, in combination with another  of its blockbuster drugs, Zyprexa, worked in conjunction to manage treatment-resistant and bipolar depression.

But Prozac went off patent in 2007, and Zyprexa, Lilly’s drug for treating schizophrenia, was set to go in 2011. How to keep the money flowing in, as patients would start taking the generic versions together?

Enter Symbyax.

Lilly repackaged the two pills into one, called it Symbyax, and received FDA approval–and a whole new patent with possibilities for extension–in 2009.

Write the authors of “Strategies for Extending the Life of Patents” in International BioPharm,

“To extend the life cycle of Zyprexa and to recoup losses due to the market entry of generic fluoxetine [Prozac], Lilly . . . developed and patented a combination product called Symbyax for the treatment of bipolar disorder, comprising olanzapine [Zyprexa] and fluoxetine. . . .The combination product Symbyax [added an estimated] $100 million in sales to the Zyprexa product line in 2003.”

Now, not everybody gets the chance to repackage two drugs as one and make a bundle. But, never fear, there are still more ways for pharmaceutical companies to hold on to their profits.

Aside from ‘me-too’ drugs, with strikingly similar compositions (think Celexa and Lexapro, both for depression), there’s always a  good reformulation, tweaking a product so that it’s slightly different–and winning an extension of exclusivity in the process. Often the purpose is less frequent dosing, or making the medications easier to administer.

Controlled releases are perhaps the most common reformulations among psychiatric medications.

Rispderdal’s long-acting Consta, administered as an intramuscular injection once every two weeks, received  its own approval, and was expected to keep Janssen’s cash flow for the antipsychotic significant through the present, even as Risperdal itself  lost patent in 2008.

All roads lead to Lilly, it seems, for they’ve been down this avenue also. In the 2010 issue of  the Journal of Pharmacy and Bioallied Sciences, the article “Patent protection strategies” clarifies that

“When Lilly faced the expiration of its patent for the blockbuster antidepressant drug Prozac, the company developed and obtained patent protection and FDA approval for a once-weekly, sustained-release Fluoxetine formulation.”

Thus Prozac Weekly become the first ever once-a-week antidepressant.

More successful was Wyeth’s reincarnation of its antidepressant Effexor. Approved in 1993, by 2007 its popularity had peaked and was beginning to wane. Time for Effexor XR (extended release), which Wyeth conveniently released in 2008.

That reformulation was so successful that currently Effexor XR makes up 14% of antidepressant retail antidepressant sales. (See “Prices, Profits and Innovation: Examining Criticisms of the Value of New Psychotropic Drugs” in Health Affairs.)

The practice is so extensive that in that Health Affairs piece, the authors note of this practice, common for at least the past 15 years,

“Thus, [new drug applications] for psychotropics were disproportionately more likely to be reformulations than to be [new molecular entities] that might have brought clinical improvement for patients who do not respond well to existing treatments.”

Look–it takes a lot of hard work, and a truly staggering amount of money–to develop a drug. Eli Lilly’s corporate blog notes that, on average, it costs $1.3 billion to bring a new drug to market. With that, they point out, you could buy 371 Super Bowl ads, 2 professional football stadiums, and pay the salaries of 1688 out of 1696 NFL players.

However, as of 2010, on the list of Fortune 500 companies, Johnson & Johnson (Risperdal) was #33, Pfizer (Zoloft, Pristiq) was #40, and Eli Lilly came in at 112. Drug makers are not suffering badly, and in fact continue to do quite well.

But the focus on keeping market exclusivity can come to dominate other causes.

Because, you see, at times it’s easy to lose focus on the ideal end results–helping patients through their psychiatric difficulties–and easy to fall into a mindset, where all that matters is the patent. . .

. . .the patent at any price.

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