Drug Truths

A site devoted to teaching about drug discovery and development.

Loss of Exclusivity of Pfizer’s Lipitor Will Also Impact AstraZeneca (AZ)

with 4 comments

Rightfully, much has been made of the expiration of Pfizer’s US patent for Lipitor (generic name: atorvastatin), which will occur by the end of this year.  Lipitor is the most notable of the statin class of lipid-lowering drugs, compounds that have helped to lower the rates of heart disease-related deaths around the world.  Lipitor’s commercial success was unprecedented.  At its peak, it had worldwide sales in excess of $13 billion dollars annually.  Even with its patent expirations in recent years in various parts of the world, it still rang up $10.7 billion in 2010 keeping it the world’s number one selling drug.

Lipitor’s success can be attributed to a number of factors, but most notably the large (and expensive!) clinical trials Pfizer carried out over a number of years that showed how the treatment of patients at risk of heart attacks and strokes have greatly reduced incidents of adverse events when treated with Lipitor when compared to placebo.  Its efficacy, coupled with its remarkable long-term safety profile, have made Lipitor a household name.

In November, when the US patent expires, generic drug makers will be able to begin selling atorvastatin (the active ingredient in Lipitor) and they will do so at greatly reduced prices.  It is not unusual for the costs of generic drugs to be 10 – 20% of what the branded drug costs.  Thus, Pfizer’s sales of Lipitor will drop dramatically, as pharmaceutical industry analysts have noted for the past few years.

What does this have to do with AstraZeneca?  Well, AZ sells its own statin, Crestor (generic name: rosuvastatin), and with 2010 sales of $5.6 billion, it is a major product for the company.  AZ has always touted Crestor as the superior compound with slightly better lowering of LDL (“bad cholesterol”) and slightly better elevation of HDL (“good cholesterol”).  Unfortunately for AZ, Lipitor had been on the market for a number of years before Crestor made it, and the differences in cholesterol modulation between the two drugs was not significant enough for physicians, who were already very familiar with Lipitor, to switch their patients to the newer drug.  Thus, Crestor, while still an important and heavily prescribed drug, trailed Lipitor.

But with Lipitor going generic, AZ has a major problem – one that is a reflection of the cost-consciousness of health care systems.  The generic price of atorvastatin will likely be one-tenth of the cost of Crestor.  Thus, payers–insurance companies, Medicare, etc.–will insist that patients newly diagnosed as needing a cholesterol lowering agent be prescribed the less expensive atorvastatin rather than Crestor.  Even more concerning will be those health care plans that will try to have their Crestor patients switched to atorvastatin in an attempt to reduce their costs.  The arrival of generic atorvastatin, therefore, not only impacts Pfizer, but might also cause a drop in Crestor sales as well.

AZ has been acutely aware of this issue for years and has tried to take steps to differentiate its drug from atorvastatin.  Interestingly, Crestor has a biologic property that differentiates it from atorvastatin – it lowers an inflammatory marker call C-Reactive Protein (CRP).  CRP is associated with a variety of inflammatory conditions, including inflammation of the arteries.  Scientifically, it is thought that high levels of cholesterol damage arterial walls and the process of repairing the artery wall results in the beginning of atherosclerosis.  High CRP levels could therefore be a signal of early atherosclerosis.

For unknown reasons, Crestor lowers CRP levels and this distinguishes it from other statins.  Is this medically significant?  AZ thought so and to prove it thecompany ran the SATURN trial.  This study  compared Crestor directly with Lipitor in measuring the build-up of plaque in the arteries of patients with heart disease.  AZ’s thinking, and hope, was that the differences in the biochemical profile of Crestor vs. Lipitor would translate into a meaningful clinical difference in slowing the progression of atherosclerosis.  If the theory held up, it would be a great result as AZ would be able to clearly show that Crestor was the superior agent.

The first results of the SATURN trial are in and, while Crestor showed encouraging trends in reducing the fatty deposits in arteries, the results were not statistically significant from the results seen with Lipitor.  AZ will be reviewing these results in depth at the upcoming American Heart Association Meeting in November.  But for now, the claim of Crestor’s superiority will likely be nullified.  In the face of the dramatic drop in price for generic atorvastatin, it will be hard for physicians to justify prescribing the less costly drug.

The Lipitor patent expiration won’t just impact Pfizer’s net sales in 2012; AZ’s Crestor sales are also going to feel the impact.


Written by johnlamattina

September 23, 2011 at 1:04 pm

4 Responses

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  1. For several reasons, this brings back a vivid memory.
    My team had just accelerated the launch of Pravastatin by three months. Walking out one evening the finance head of my division congratulated me on this and asked why I was not more upbeat. I commented on early trial results of another statin at Warner-Lambert that had better LDL lowering, (and a far lower cost basis), and was concerned how it would play out. He noted that he was hearing nothing but upbeat prospects for our drug and no one else in the firm was worried, or even commenting on this “slight risk”. Told me not to worry.

    Seems like a time warp in that the same themes are playing out again; potency, efficacy, and costs. What is new is the CRP-link. Is there any indication of causality for any benefits? For instance, might there be outcome differentiation in patient cohorts with smaller lipid particles? This is thought to be associated with inflammation and patients showing greater arterial disease progression. Maybe a segmentation strategy will play out there, but the cost advantage of generic atorvastatin will be persuasive, as you project (given the market temperament.)


    September 23, 2011 at 2:40 pm

    • What a great story! Thanks for sharing. Your time warp questions are also spot on. My guess is that to answer these will require outcomes study that no company will be willing to take on. – John


      September 23, 2011 at 3:28 pm

      • Lipid particle size is a common analysis now, and there may be some genomic-predictors as well now. I wonder if the recent huge trials included that data dimension – they can always re-mine the data. Results may tehn come up in Nov.

        On a broader view – I wonder if firms are thinking of using biobanked clinical trial samples for this kind of angle? In the case that the protocol “missed” that kind of dataset (new insight; particle size,…) New assays are being invented faster than new therapies, so this could perhaps recover some of that huge trial investment/risk.


        September 23, 2011 at 5:50 pm

      • Terry,
        Rumor has it that AZ will be rolling our more analyses on the SATURN trial at the AHA meeting in November. It will be interesting to see whether they have done any of this. – John


        September 23, 2011 at 6:01 pm

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