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A large number of expensive, but highly profitable branded prescription drugs will go off-patent

in the USA between 2011 and 2015. Their revenues are crucial to fund the immense costs

associated with the development of an innovative drug. The rising cost pressure on

pharmaceutical stakeholders has increased the demand for more affordable medications, as

provided by the branded drug's generic counterpart. Yet, research based incumbents are moving

beyond the traditional late lifecycle strategies and deploy more aggressive tactics in order to

protect their brands, as seen with Pfizer's Lipitor!. It is doubtful, whether these efforts will help

the blockbuster business model to resist current market conditions.

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Keywords: US pharmaceutical industry, counter-generic strategy, extended lifecycle, Lipitor!

1. Introduction

3

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The pharmaceutical industry has reached a turning point in its history, which is commonly

referred to as the "patent cliff" and marks the end of Big Pharma's blockbuster1 business model

[1,2, p. 8]: Between 2011 and 2015, several hundred branded prescription drugs of a combined

annual sales value of US$170 billion [3] –that is more than 80% of Portugal's 2012 GDP [4]– lost

and are going lose patent protection. Among them are 60% of the US Top 10 selling drugs in

2011, as shown in illustration (ill.1).

Illustration 1: US Top 10 pharmaceutical prescription drugs by sales in 2011 of a combined annual sales

volume of almost US$33 billion losing patent protection in the USA [5].

Many key therapeutic classes, such as high cholesterol, will be dominated by cheap generics, that

address the main stakeholder's needs more effectively than the research-based industry leaders.

!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!D!Note that words printed in bold either indicate industry specific terms explained in the glossary (appendix) or highlight important facts in order to ease reading and comprehension.!

1. Introduction

4

Within six months, most branded blockbuster drugs will lose 80% market share in the respective

molecule market [6]. Industry leaders are consequently left with a huge financial gap, because it

is not unusual that branded blockbuster drugs account for 25% and sometimes even 50% of firm

revenue (ill.1). What appears to be a nightmare for marketers, has become reality for Pfizer's

ultimate cash cow, the cholesterol-lowering pill Lipitor!. In 2011, the world's best selling

branded drug in history lost patent protection in the USA and was handled as the greatest generic

opportunity that ever existed [1].

In contrast to generic firms, however, it is research-based pharmaceutical companies that drive

medical progress through their innovations and thus benefit therapeutic advancement [7]. A

steady cash flow is a necessary condition to further justify and fund R&D investments, since de-

velopment of an innovative drug with associated costs of US$1 billion is very expensive [8].

With empty pipelines, however, research-based pharmaceutical firms will need to focus on

extending the product lifecycle of already approved blockbuster drugs with counter generic

strategies in order to recoup R&D expenditures [9, p. 225]. Each additional day of market

exclusivity can earn the company as much as US$13 million [10, p. 18].

Under those circumstances, the following work project will investigate why the patent protected

term is crucial to branded drugs and what strategies a firm has available to counter generic

competition. The focus will hereby lie on the USA as the world's largest market for prescription

drugs [11]. In order to give the reader a key understanding, a short key figure overview of the US

pharmaceutical market will be provided. It follows a brief introduction to the political and

regulatory market environment stressing the influence of diverse stakeholders that further

increase the complexity a pharmaceutical firm is operating in. It will be shown that the

pharmaceutical lifecycle follows a trichotomy consisting of a tedious, costly and risky

developmental stage, a monopoly-like commercial period and a late post-patent stage, when

generics will conquer the market [12]. The most popular patent extension strategies to minimize

branded sales erosion will be presented and classified in terms of timely impact, nature and

2. Market overview

5

popularity. The second part of the work project will deal with the patent expiry of Pfizer's

Lipitor!. After a short introduction to the respective therapeutic class and a brief history on

Lipitor's! commercial life, tactics deployed by Pfizer to protect its blockbuster drug sales will be

presented and evaluated in terms of effectiveness. The conclusion will question the current

research-based pharmaceutical business model.

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The pharmaceutical market can be divided into two segments: Over-the-counter (OTC) and

prescription (Rx) drugs. OTC drugs are prescription-free remedies that can be obtained at any

pharmacy and grocery store. Rx drugs, on the other hand, are pharmaceuticals that are available

at doctor-prescription only and are solely distributed at pharmacies or hospitals as part of the

patient treatment. The logic behind this classification is that some conditions can be treated

without a doctor's guidance, such as a mild cold, while others require the supervision of a

physician like heart disorders [10, p. 5f.]. Generics are a third group of pharmaceuticals, that can

be found in either of the two market segments: Generics are chemically identical and

undifferentiated copies [13] of the branded OTC or Rx product and are much more affordable,

given their availability at 1/10 of the original's price [14].

Illustration 2: Key US pharmaceutical market figures with total volume [15, p. 21/30], total value

[15, p. 21] and Rx value [15, p. 27] and volume in 2011 [16, p. 10] and 2015 [16, p. 13].

2. Market overview

6

The first part of ill.2 displays the US pharmaceutical market share in terms of volume and value

between OTC and Rx drugs. Although only every fourth pharmaceutical sold in the US is a

prescription drug, Rx drugs almost conquer all market value, since branded Rx drugs are on

average thirteen times more expensive than OTC remedies [17]. The second part of the graph

further splits the Rx market into branded and generic drug sales and displays the increasing

dominance of generics.

Research-based pharmaceutical companies –also referred to as Big Pharma or incumbent in this

paper– such as Pfizer have earned a tremendous amount of money by developing and marketing

branded Rx drugs with margins of up to 90% [18]. Some of them had lifetime revenues of over

US$140 billion within 10 years thanks to the legal monopoly branded drugs hold during patent

protection [19]. Patents are in fact the pharmaceutical industry's foundation and are issued upon

application by the national government [20, p. 81]. With drugs, the most important patent

protects the molecule, which is a chemical compound identified to treat a specific symptom or

condition. The internationally standardized patent protection term is 20 years starting with the

date the patent is filed [9, p. 230 f.] Deducting the period of drug development, a branded drugs

has available a ten year market exclusivity on average, which is given in exchange for the

substantial investment related to the drug discovery. This is a relatively short time in which the

research-based company can extract monopoly rents from its branded remedy before patent

expiry [20, p. 87]. It is the company's chance to build considerable brand equity and goodwill [9].

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The health care system in the US can be defined by a triangular structure, which encompasses

three stakeholder groups that can substantially impact business operations: The patients, who

require medical care, the providers, who give medical care and the payers, who finance medical

care (ill.3) [21].

Health care –as a public good– is either funded by government programs or private insurance

3. Regulatory and political environment

7

plans [12]. Government programs cover round about one third of US Americans and are only

accessible by low income or disabled people and seniors. Most US citizens are privately insured

through their employers. Those employers finish contracts with private insurance companies [21].

When purchasing an insurance covered prescription drug, the insured person is asked for a co-

payment. This is a small fixed, non-refundable amount the consumer needs to pay, while the

insurance company will pay the remaining drug retail price. The patient is charged a different

level of co-payment depending on the type of drug purchased: With generics, the patient's share

usually is US$10 or less. Out of pocket costs for branded products, on the other hand, are either

US$25 or US$50 depending on the drug's placement on tier two or three, which is subject to the

individual insurance plan [22]. In order to promote generics, their co-level payment has only

increased slightly with time, while branded drugs have become more expensive to patients (ill.3)

[23, p. 7].

Worldwide, the US has the highest health care expenditures, accounting for 18%2 [24] of the

nation's GDP and increased by more than 1000% between 1980 and 2010 from US$217 billion to

US$2,18 trillion per year [25]. The trend of escalating drug expenditures will continue given the

demographic transition with elderly usually requiring more health care services than young

people [26]. This development will not only put further pressure on the government's public

health care programs, but also increase the financial burden of private customers and employers

[27]. This is because insurance companies tend to pass on the rising health care costs by

demanding higher premiums and co-payments. The arising need for a more inexpensive solution

to costly branded pharmaceuticals has thus fostered the generic business boom [20, p. 39].

National laws, regulations and campaigns have been implemented to further encourage the use of

generics instead of brands [9, p. 226]. Those efforts aim at controlling costs and satisfying health-

care demand at a more reasonable price. In fact, thanks to the Hatch-Waxman Act enforced in

1984, an estimated US$1,2 trillion have been saved through the usage of generics between 2003

!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!C!In comparison, other developped countries spend 8-11% of their GPD on health care.!

4. The pharmaceutical product lifecycle

8

and 2012 [28]. This legislation encourages generic manufacturers to challenge the branded drug's

patent at any time, so that the research-based manufacturer would lose its market exclusivity and

cheap generics could sooner enter the market. This process is triggered by a 180 post-patent

market exclusivity reward that is granted to the first generic manufacturer that successfully

challenges a branded drug's patent and is approved by the Food and Drug Administration (FDA)

[9, p. 232f.,29, p. 261]. Those are six very profitable months for the first generic, since limited

competition allows for fairly high drug prices.

The FDA is the federal regulatory body responsible for the protection of public health. Each drug

company, that wants to sell its treatments in the US –indifferent of being a branded prescription

and OTC drug or a generic version of them– needs FDA approval. In order to make a decision on

market authorization, the FDA will examine the drug's clinical study results [30].

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Illustration 4: The product lifecycle of a branded prescription drug [20, p. 41,10, p. 15,31, p. 41].

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The product lifecycle of branded Rx pharmaceuticals is different from the standard marketing

model. In most cases, an approved drug undoubtedly passes the four different stages –intro-


9

duction, growth, maturity and decline– as suggested by the standard scheme. The extended

pharmaceutical model however encompasses two more lifecycle periods [20]. Especially the

developmental stage is crucial to understand Big Pharma's dependency on branded blockbuster

revenue and their efforts to protect them in the late post-patent period. Given the number of

stakeholders and market influences the lifecycle shape and duration is fairly unpredictable: Latest

clinical trial results or changing regulatory requirements can essentially alter a drug's life [12].

Ill.4 displays the typical pharmaceutical lifecycle for a branded mass-market prescription drug

with its three different periods. Those are presented in the following.

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A drug passes several phases in the R&D process that are briefly specified and characterized in

terms of time, investment and risk in ill.5.

Illustration 5: The drug discovery process with sub-phase description [32,33,34,35], time, risk [36, p. 6]

and cost characteristics [37,38].

It takes ten years on average from the discovery of a new chemical molecule to the resulting

drug's market introduction. Since research-based pharmaceutical companies all use the same

chemical databases for the identification of a suitable molecule to treat a specific condition, they


10

are advised to file a patent as soon as possible. Firms otherwise risk to have the exclusive market

rights reserved by a competitor, who is equally eager to identify the chemical mechanism that

could earn its company billion of dollars [10, p. 17].

In 2011, pharmaceutical companies accounted for 20% of all R&D expenditures spent by US

businesses, that is US$67 billion in absolute numbers [39, p. 5]. Despite this billion dollar budget,

return has been minimal [40]. Expenditures for drug development increased by 90% [41] while

the approval rate of new molecular entities –a metric for R&D productivity– dropped by almost

18% compared to 15-20 years ago [42]. One reason for the development is that it becomes

increasingly difficult to develop drugs that are superior to existing treatments. Likewise, approval

standards for a drug's market introduction have become increasingly stringent due to safety

concerns that were triggered by drug scandals as the case with Merck's blockbuster drug Vioxx!

[23, p. 8]: In 2004, the very effective rheumatism treating drug was instantly taken out of the

market, after press revealed that the use of Vioxx! was linked to at least 55,000 deaths in the US.

Even more astonishingly: Merck knew its drug was fatal, but used statistics to hide the pill's

dangerous side effects in order not to jeopardize market approval [43,44]. That some

pharmaceutical companies knowingly and willingly act unethically can be explained by the fact

that sunk costs for the drug development increase as time passes: A phase III failure is with

almost 95% of total development cost spent considerably more expensive than a preclinical one

(ill.5). Given the significant amount of drug development, it is in the company's interest to push a

promising product to the market, even if data reveals negative surprises in the drug's safety

profile [36].

Considering that only one out of 10,000 substances explored will receive market approval,

attrition rate is high and investment risk enormous (ill 5). A Forbes article offered some

perspective on how attrition drives development costs [45]: Astra-Zeneca suffered from several

developmental failures, so that average costs of new drug development has been escalated to


11

US$12 billion, which is ten times higher than the average of US$1 billion3 [41,46].

Even if a branded drug masters market approval successfully, it does not mean that it will

generate sufficient revenue to cover its R&D spending: Only one third of approved branded drugs

is able to fully recoup their pecuniary investment [10, p. 19]. Hence, the research-based

company's top performing products also need to compensate for approved drugs that have not

enough financial strengths or those that have never been approved.

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12

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component, as prescription drugs can only be dispensed by pharmacies, hence prohibiting firms

from directly selling to the consumer [10, p. 5f.]. It will therefore not further be considered.

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The actual turning point in a drugs life however is the entrance of generic competition, as a

consequence of patent expiry. Given that generic producers can challenge a patent at any time in

the USA (Hatch Waxman Act), they might even enter the market prior to the regular patent

expiry. Generic companies rely on the incumbent’s intellectual property, which is why they do

not have to repeat expensive clinical studies for their products [2, p. 5]. This absence of

substantial investments and liability decreases entry barriers and allows generic firms to solely

compete on price [9, p. 225, 231,29, p. 261].

As generics enter the market, branded profits erode quickly, since demand is shifted to the

cheaper generic alternatives. The higher the number of competitors, the more will price levels

approach marginal costs [9, p. 227]: In case no generic manufacturer is granted the 180 days

market exclusivity after patent loss, several generic competitors will simultaneously enter the

molecule market, causing a prompt price drop of 80% [48]. Elsewhere, prices remain fairly high

and only decrease by 10-15% [49] in the first six months due to limited competition. In either

case however, 90% of branded prescription volume in big therapeutic classes will be substituted

by generics within 12 months after patent expiry, provoking a 65% decline in branded drug's

5. Counter generic strategies

13

revenue [10, p. 47,48].

Against this background, it is estimated that each additional day of market exclusivity earns the

firm US$1.3 million, with blockbuster drugs it is even US$13 million [10, p. 18]. Hence, apart

from maximizing sales during the drug's commercial life, a firm should apply tactics that either

prolong market exclusivity or soften the impact of generic competition [9, p. 227].

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Research-based manufactures have a number of options available to extend the commercial life

or protect the revenues of their brands. Literature provides many approaches to classify those

strategies [10, p. 75ff]. The existing lack of consistency in strategy systematization gives a

chance for a self-conceptualized classification model, as displayed in ill.6.

Illustration 6: Most popular [50] counter generic strategies deployed by research-based manufacturers in

terms of impact [9, p. 227] and nature [10, p. 80].

The model above distinguishes three strategic categories –legal, marketing mix and business


14

model related actions– and characterizes their sub-strategies in terms of timely impact on generic

competition (x-axis), nature (y-axis) and popularity of usage (size of geometrical form). Note that

those options represent not all, but the most popular counter generic strategies.

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Drugs have multiple patents protecting it. While the most important patent covers the molecule,

there are other elements that can be patented as well, like the method of manufacturing or newly

approved indications. Those secondary patents are often filed in the later commercial life in

order to raise barriers of entry for generic competitors. The popularity of strategic patenting has

increased over time, given that a branded drug nowadays can be protected by up to 40 different

patents, compared to only two patents 20 years ago [9, p. 248f.,10]. The higher the number of

patents, however, the increased the likelihood of a technical defect with one of those patents,

which is a promising starting point a for a successful patent challenge [10, p. 80]. If a generic

firm challenges one of those patents in court at any time, the incumbent is likely to defend the

brand's intellectual property. The majority of those litigations is settled out of court: In exchange

for a payment or other concessions by the branded manufacturer, the generic firm will either drop

the patent challenge or postpone generic market entry [20, p. 107ff]. The latter applies if one

generic manufacturer was granted a six month exclusivity period. There have been settlements

that delayed generic competition of up to 10 years [51], virtually doubling the branded drug's

commercial monopoly period. Those arrangements are highly controversial given the antitrust-

like character [52]. Generic settlement is nevertheless the only tactic that effectively prevents

generic competition for a certain period of time – 5 years on average [51] – and is thus the most

popular one.

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Albeit marketing expenditures for the branded drug typically drop by two thirds as patent expiry

approaches, 40% of research-based companies use promotional tactics to combat generic

competition [9, p. 237]. Promotional effort in the late stage of the drug's lifecycle is often


15

targeted toward stakeholder that influence the final dispensing decision, because as soon as

generics enter the market, the health care system seems to rather focus on cost than value. The

US is a payer-controlled market which is why promotion in the late stage focuses on both,

insurance companies, that bear the major part of pharmaceutical costs, as well as patients, that are

charged a higher co-payment for branded drugs (ill.2) [20, p. 188f.]. The purpose of promotional

programs targeting the end-customer is to further strengthen brand loyalty by advertisement

while simultaneously lowering end-user's financial exposure with co-payment coupons [53].

Payers are also addressed with financial incentives.

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In the US, price is the least regulated marketing variable and plays the key role with the generics'

cost leadership. The more effective a branded drug, the higher the price it can charge. The

argument of effectiveness however is nullified when generics enter the market and offer the same

drug at a substantially lower price [20, p. 194]. Strategic pricing has become a key focus for

research-based companies, since payers try to reduce health care expenditures [54]. The

incumbent will either decrease or increase the drug's price –maintaining the current price level is

usually no option. By charging a price premium, the branded manufacturer will accept to lose

the price-elastic segment to generic competitors. Instead, it will focus on the cost-insensitive and

loyal customers and retain a low, but highly profitable market share in order to offset part of the

decline in sales volume [9, p. 228]. In contrast, the incumbent can also decrease the costs of

therapy either by directly lowering the drugs' retail price or by giving volume rebates.

Discounting has a more aggressive character, because it nullifies generics' competitive advantage,

as long as the firm is able to decrease prices by the same magnitude of generic competitors [20, p.

194f.]. Given that very loyal customers are likely to stay with the brand for an extended period of

time, the value extracting tactic is attributed a longer term impact than a price decrease.

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Line extension tactics try to improve the brand's clinical profile in terms of efficacy, side effects


16

or patient compliance in order to differentiate it from generics [20, p. 116f./169]. Given that the

incumbent knows the market very well, it can more effectively respond to unmet needs and thus

provide a higher value to patients [9, p. 229]. In the past ten years, almost one third of newly

approved drugs in the US have been reformulations such as easy-to-swallow pills. That tactic

encompasses changes in the existing drug's form or dosage, which allows for more flexibility and

better customization [20, p. 140]. Combination drugs on the other hand are fixed formulations

with two molecules. They help patient convenience, as they only need to take one pill instead of

two. In order for this tactic to be successful, the number of patients that receive both medications

at the same dosage must be large enough, otherwise the additional costs of development will not

pay off [20, p. 152ff.]. Additional clinical studies are required for all line extension tactics and

often help to identify new indication areas for the branded drug [55]: Viagra!/ Pfizer, for

example, was originally developed to treat angina and later approved for erectile dysfunction [9,

p. 245]. Indications expansion deals with the process of identifying new areas of therapy for the

approved drug apart from its current indication. Drugs approved for multiple indications need to

carefully consider pricing strategies in the various markets in order to prevent the risk of

arbitrage. Besides, this tactic does not prevent doctors from prescribing generic off-label for the

newly approved indication [20, p. 126]. This is a major threat with all four product line extension

tactics: Only the new invention will be granted an additional market exclusivity of either three

years (new indication reformulation) [9, p. 245], five years (combination drug) [56] or seven

years (next generation) [57, p. 2.4]. Hence, the respective tactics will contribute little to defend

sales of the original after patent expiry. The ultimate purpose of a product line extension is

therefore to either switch as many patients as possible to the modified original or to extend the

existing market to exploit brand potential. One could even speak of a planned cannibalization, as

is the case for next generation drugs that can be seen as follow-on product [10, p. 94].

I%&,.4.(94,4%0'#(

The research-based manufacturer is allowed to introduce or license a generic version of its


17

branded drug –also referred to as authorized generic or fighter brand– at any time. This also

applies for the 180 days exclusivity period, which is granted to the first generic manufacturer to

successfully challenge a branded drug's patent [9, p. 242].

The approach enables the company to drive different pricing policies without harming brand

perception: The original brand might experience a price premium in order to increase profit-

ability. The fighter brand, on the other hand, may be simultaneously sold at a significant discount

to capture part of the price conscious segment that would otherwise been completely lost to

generic competitors. This allows the incumbent to expand the market and sustain an ongoing

return on investment – though at a lower profitability – over a longer period of time [20, p.

198ff.]. The tactic's timely impact depends on the firm's decision on whether it wants to engage in

a price war (the longer) or not (the shorter the generation of additional sales). Branded generics

sales help to fully utilize existing manufacturing capacity. That way, the incumbent will not

compromise economies of scale benefits, that would normally vanish with generic competition

related sales erosion [20, p. 201]. Given that generic companies "have the right relationships, the

right [massive] portfolios, the right selling structures and mind-sets" [20, p. 201], they are best to

commercialize the copied brand manufactured by the research-based company. That may be the

reason why the tactic is only applied by 28% of research-based companies (ill.6).

8H($-(J?C(#60$'@(

The OTC switch describes the process of launching an OTC version of the original Rx drug in the

consumer market [10, p. 96]. Severing the prescription-free market however requires different

skills and expertise –as the case with branded generics. One difference to the Rx drug segment is

that pharmaceutical branding is much more effective, since the consumer takes the buying

decision. The OTC switch adds an additional stream of revenue by capturing patients that

typically would not go to see a doctor. Apart from an additional three-year market exclusivity

period (ill.6), prescription-free drugs represent long-term opportunities [20, p. 178ff.]. Listerine!

(Johnson & Johnson) for example, is sold over the counter since 1914 and still generates high

6. Context of the case – the anti-cholesterol market and Lipitor's! History

18

sales, exceeding US$1 billion in the US alone [58,9, p. 243]. An OTC switch will only be

approved if the company can successfully prove patient's well-being and safety under self

medication circumstances. This may not be feasible for brands of therapeutic classes with less

perceptible symptoms [20, p. 185]: Patients that suffer from high cholesterol, for instance, do not

instantly feel the benefits of their treatments, "nor do they feel the consequences of not taking it"

[20, p. 179]. In order to further increase a drug's qualification for self-management purposes,

lower dosage strengths are often introduced to the OTC market, because they cause fewer side

effects [20, p. 180]. Cannibalization effects are only expected when patient's co-payment for the

prescription drug exceeds the cumulated package price of OTC drugs necessary to replicate the

prescription dosage [20, p. 191].

K*(C-,$4H$(-A($@4('&#4(–($@4(&,$0L'@-:4#$4%-:(=&%34$(&,.(!"#"$%&'(! (M0#$-%;(

Cholesterol is a type of fat that is produced by the liver and found in animal products, such as

meat, milk or eggs. High cholesterol clogs arteries and hinders the blood from flowing through

the body. This can cause coronary artery disease, the most common type of cardiovascular

disorder responsible for heart attacks and strokes. The probability of suffering from high

cholesterol rises with unhealthy eating habits, obesity and age [59]. About one third of the US

population suffers from high cholesterol [60]. Furthermore since medication cannot cure, but

merely treat the disorder, market potential is huge [61].

Statins are the most effective drug class in fighting high cholesterol. The most common statin

molecules are simvastatin and atorvastatin. The first statin was Mevacror!, chemically known as

lovastatin, developed by Merck and introduced in 1987. It steadily lost its dominant position, as

other superior statins entered the market. Ten years after its introduction, Mevacror! hardly

had a 10% market share, although its patent was only going to expire in 2001. Merck meanwhile

developed a drug of a second statin class, simvastatin, that was branded and commercialized as

Zocor! in 1992. Zocor! was more effective than existing statins and within five years it had

6. Context of the case – the anti-cholesterol market and Lipitor's! History

19

become the market leader holding a 40% market share until Lipitor! was launched [62]. Apart

form the second best selling statin drug that time, Pravachol! (pravastatin)/ Bristol-Myers

Squibb and the less successful Locol! (fluvastatin)/ Novartis, Lipitor! entered the US market

fifth in early 1997, introducing another high-potency statin class, atorvastatin [63, p. 1]. Just 18

months after its introduction, Lipitor! had taken market leadership in the statin market (ill.7) and

was about to become the world's best selling drug in history, turning Pfizer into the world's

largest pharmaceutical firm.

Lipitor! was developed in the early 1990's. The patent for its atorvasatin molecule was filed in

March 1990 in the US, granting it a 20 year protection until March 2010. Thanks to a fast track

strategy, it was FDA approved in December 1996 and legally left with 13 years and three months

market exclusivity [62]. Much of Lipitor's! success can be attributed to its excellent clinical

studies, that confirmed its higher effectiveness, involving more than 80,000 patients4 [63, p. 1].

Safety is key in the pharmaceutical industry, which is why this extensive clinical program

established reliability and trust among prescribers. In addition, the investigation of different

dosages within those 400 clinical studies helped physicians to better determine the suitable drug

strengths for a broad range of patients, facilitating their daily business [63, p. 1,64]. Lipitor! was

thus positioned with a convincing value proposition of superior therapeutic performance and

convenience. This combined with Pfizer's marketing skills helped to establish Lipitor's! as the

dominant drug in its class. Pre-marketing efforts included a cholesterol education campaign and

the identification of key opinion leaders. Pfizer pushed for a fast market penetration and targeted

prescribers with the statin market's largest sales force. It additionally deployed a moderate pricing

strategy for Lipitor! by pricing it slightly below the three leading competitors (ill.7). This

together with the favorable clinical results, was a winning combination [62]. Lipitor's! annual

sales peaked at more than US$13 billion in 2006, occupying almost half of the statin market

(ill.7) [65]. When Zocor! however lost its US patent protection the same year, market dynamics !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!4 Clinical studies usually only encompass some tousand patients (ill.5).

7. Strategies deployed by Pfizer to protect Lipitor!

20

changed dramatically. Sold at a 40% discount, generic simvastatin quickly gained market share,

and –although a more effective statin –also affected Lipitor!: Its statin market share dropped by

18% from 44% in 2006 to 26% in 2009 [66]. This result exemplifies well that key pharmaceutical

stakeholders value costs savings over therapeutic benefit. In less than a year lost blockbuster

Zocor! almost all of its market presence. The same was going to happen to Lipitor! in early

2010, when the branded drug's US patent was going to expiry in its most important market. Until

then, Lipitor's! cumulated global lifetime sales added up to US$118 billion [65]. Part of its

lifecycle is summarized in ill.8.

Illustration 8: Lipitor's! commercial life and counter generic tactics deployed [67].

N*(G$%&$4904#(.4<:-;4.(";()*"+,&($-(<%-$4'$(!"#"$%&! ((

Pfizer did not leave the atorvastain market to generics without a fight. It deployed a variety of

counter generic tactics –as summarized in ill.6 and ill.8– in order to defend branded sales [68].

Pfizer's goal was to retain at least 40% of the combined prescription market share for Lipitor!

and its authorized generic for at least six months after patent expiry [69].


21

F&;(A-%(.4:&;(

In 2003, Indian-based Ranbaxy Pharmaceuticals, was the first manufacturer to successfully

challenge one of Lipitor's! patent and was consequently entitled to sell its generics exclusively

during the 180 days post-patent period. Since then, Pfizer has been suing Ranbaxy in court to

infringe patent rights related to the manufacturing process of atorvastatin. Five years later, the

two companies eventually settled the case out of court and agreed to delay the introduction of

generic atorvastatin to the end of November 2011 [63, p. 2]. In return, Pfizer would stop blocking

Ranbaxy's efforts in introducing its generics and additionally granted Ranbaxy the right to sell a

generic version of Pfizer's less successful combination drug Caduet! seven years before its

actual patent expiry [27]. This settlement earned Pfizer an extra 20 months of exclusivity

associated with an additional US sales of almost US$10 billion (ill.8).

F%-=-$0-,(

In 2010 Pfizer launched the discount program "Lipitor! for you", that was heavily promoted

through leaflets, TV ads and a website, whose subscription numbers of 750,000 US Americans

[63, p. 3] exceeded Pfizer's expectations [70]. Advertisement aimed at emphasizing positive user

experience and encouraging repeat purchases with messages as "If Lipitor! has been working for

you, stay with it" [8].

The program was supported by a US$250 million DTC advertising budget in 2010 and US$220

million in 2011 respectively [71], maintaining Lipitor's! status as the most promoted Rx drug in

the US market5 [2]. Given that the average annual DTC spending for Lipitor! accounted for

about US$275 in previous years [2, p. 13], these are 2010/11 DTC marketing expenditures are

significant and unusually high for a product only some months ahead of patent loss [54].

A co-payment offset card was the core of the "Lipitor! for you" campaign and an effective

incentive to strengthen customer loyalty. The drug-maker funded coupon card reduced privately

insured patient's exposure when purchasing a monthly supply of Lipitor! from US$25 or US$50

!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!5 Note that the average budget of the most advertised brands in 2011 was US$100 billion [71].


22

to as little as US$4 [63, p. 3]. "People getting a month of lifesaving medicine for the price of a

cup of Starbucks is…pretty impressive," noticed a research director [70]. In fact were those US$4

well below the usual co-payments for branded drugs or even generics.

F%0'4(

Pfizer deployed both, a retail price increase for Lipitor! –that was higher than the annual

inflation– followed by a steep discounts for insurance companies prior patent expiry (ill.9).

Retail prices for a 20mg monthly supply of Lipitor! went up by 18% in 2011, compared to

2010’s cost of therapy. That increase was higher than the accumulated price increase between

2006 and 2009. The absolute average monthly costs of therapy in 2006 were US$108 and

US$162 in 2011. That is a price increase by more than US$50 in absolute or 50% in relative

numbers within five years. In 2012, retail prices for branded Lipitor! further increased sharply to

US$178, indicating that Pfizer is targeting the highly profitable price-inelastic segment. The

pricing policy of the final third in Lipitor's! patent protected life is summarized in ill.9.

Given that the US$4 co-pay coupon card was available at website subscription only, Pfizer

reached about one third6 [72] of those patients that have been prescribed Lipitor! in 2011. The

remaining insured consumers though were charged up to US$50 co-pay for a monthly supply of

Lipitor!. In order to prevent those patients from switching to the less expensive generics, Pfizer

spent years negotiating unusual rebate agreements with insurance plans [22]: The company

offered Lipitor! at heavily discounted retail prices to keep the drug competitive with generic

alternatives. In exchange, insurance companies would effectively block the distribution of generic

atorvastatin for six months after Lipitor's! patent expiry until May 2012 [27]. They prevented

pharmacies from dispensing unbranded copies by simply rejecting generic atorvastatin claims

[73]. Some insurance companies, accepted the deal and further moved Lipitor! to the lowest-co

payment tier, offering customers the branded drug as cheap as the generic counterpart [74]. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!I!This percentage is based on 24 million units of Lipitor dispensed in 2011 divided by 11 (yearly supply ! 11 months, considering patients may forget to take the medication) with 750,000 people having subscribed to the "Lipitor! for you" website in order to obtain the US$4 co-payment coupon.!


23

!/$@-%0O4.(94,4%0'#((

In 2011, Pfizer formed a partnership with Watson Pharmaceuticals, a generic manufacturer, to

market and distribute an authorized, Pfizer manufactured generic atorvastatin until 2016 [75]. In

return, Watson paid Pfizer a 70% royalty on generic Lipitor!-related sales [63, p. 3]. The

branded generic was launched at the same time as Ranbaxy’s generic entered the market and was

sold at a 50% discount [75]. As suggested in the theoretical presentation of counter generic

strategies, Pfizer's authorized generic version could capture almost half of the generic atorvastatin

market in the first six months and hence mitigate financial impact of generic competition (ill.10)

[76].

8H($-(J?C(#60$'@(

Pfizer is currently conducting a Phase III clinical study with a 10mg Lipitor! version in order to

assess patient’s ability to autonomously lower their cholesterol levels. If clinical results are in

favor of Pfizer, Lipitor! will be the first non-prescription statin, with a projected US$1 billion

annual sales perspective. Yet, there are long-standing obstacles that dampen hopes for an

extended life in the OTC drug market [77]: In 2000, 2005 and 2007 respectively, the FDA

rejected to approve a non-prescription version of Merck's Mevacor! –the first developed statin

[78, p. 2]. Although the research-based company submitted the most favorable consumer usage

studies to date, concerns about the customer’s ability to manage and monitor the pill’s intake

correctly and sufficiently dominated [61, p. 8].

P5&:/&$0-,(-A()*"+,&'(($&'$0'&:(4AA4'$054,4##(

Ill.10 shows the US market share development of Lipitor! and its two generic equivalents in

the atorvastatin market. Within six months, the branded prescription volume tumbled down from

originally 100% in November 2011 to 30% in May 2012. Although Pfizer's blockbuster lost

plenty, data suggests that Lipitor! could preserve a higher market share than the usual off-patent

blockbuster, whose prescription share six months after patent expiry accounts for roughly 20%

(ill.10). Given that perspective, Pfizer's counter generic strategy can be evaluated as successful.


24

This conclusion is further supported by a simple calculation: In the first six months after patent

expiry, Lipitor! gained additional US sales of US$1,4 billion [72] at an average market share of

35% (ill.10). If Pfizer had just retained 10%7, the branded drug had just generated US$0,4 billion.

That is a difference of US$1 billion or the costs associated with the development of one branded

drug. By the end of 2012, Lipitor! still owned a 18% volume market share. That is three times

higher than usually the case. Apart from its successful protection in branded market share, Pfizer

also achieved its goal of maintaining a combined market share of at least 40% at the end of the

six months period: Together with Watson's authorized generic, Pfizer captured more than half of

the atorvastatin market in May 2012. This share was relatively profitable given that Watson didn't

engage into a price war with Ranbaxy [79].

Illustration 10: Prescription share (volume) of the US atorvastin market in 2011/12 [76,80, p. 21,81].

When a branded drug's patent expiries, the original manufacturer typically shifts resources to

newer products. Pfizer didn't because of two reasons: First, Lipitor! –that accounted for more

than 15% of Pfizer's revenue in 2010 [82, p. 20/25]– was too valuable to be casually abandoned.

Second, with no new blockbuster in pipeline to fill the financial gap, Lipitor! was about to leave,

!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!7 This assumption is feasible given Ranbaxy's drastic price cut (see page 25).


25

Pfizer could not shift resources to focus on newer products. Instead, the industry leader kept

marketing expenditures nearly same level as previous years and deployed an unprecedented and

aggressive mix of counter generic strategies in order to extend market exclusivity and maintain

some revenue of its multi-billion dollar brand (ill.6) [47].

Pfizer's strategy worked given the following reasons. Albeit Ranbaxy challenged Lipitor's!

patent successfully, Pfizer started an exhausting legal dispute, blocking Ranbaxy to introduce its

own generics. Its successful defense and settlement preserved the branded incumbent multiple

years of otherwise lost patent protection. It further saved the company 20 additional months of

competition-free revenue, that quickly recouped litigation costs [83].

Pfizer further understood the needs and motives of consumers and did not underestimate the

growing influence of payers over prescription decisions. Payers usually cannot afford to have

patients staying on the more expensive branded-product, once generics are available. Thus, Pfizer

offered Lipitor! at a likely 85-70% discount8, in order to nullify the projected 10-15% price

advantage the first generic entrant was typically to bring [22]. When Zocor! (simvastatin) lost

patent protection in 2006, the price for generic simvastain had only dropped by 19% six months

after patent expiry. Only later, when more generic manufactures entered the market it declined by

60% [66]. Against these circumstances, the six-months-post-patent deal seemed feasible for

insurance companies. Besides, given the preceding 50% price increase within five years, Pfizer

could stay competitive and didn't lose much with those agreements [63, p. 5]. Eventually, it

turned out that Ranbaxy sold its generic atorvastatin at a 60-70% discount during its 180 days

exclusivity period. So insurance companies were left contracted to pay a discounted, but higher

priced branded Lipitor! [79]. "The Lipitor! for you" couponing program has further been a

convincing argument for patients to stay with Lipitor! –or even switch from other statin brands

–since practically none branded prescription drug was available for as little as US$4. Key to

!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!8 Given the intransparency of contracting conditions, the actual extent of the actual discount is unknown, but likely to be between 15-20%.

8. Conclusion and further thoughts

26

Pfizer’s counter generic strategy was the six months period following patent expiry when only a

single generic competitor had entered the market. As soon as Lipitor! faced multi-source

competition, this model did not make financial sense anymore [84]. The environment had become

"much more hostile" [85], putting Pfizer into a position where it was to become "lead payer for

branded Lipitor!" [86], if it did not stop co-pay coupons and rebates: 181 days after Lipitor!

went off patent, four more generics became available offering atorvastatin for as little as 4% of

the original’s costs of therapy [87]. Hence, it is only intuitive that Pfizer announced to stop its US

promotional activities for Lipitor!, including further contract negotiations with payers, in early

June 2012 [85].

As one can tell from ill.6, Pfizer primarily selected short-term tactics, which is why it could

only temporarily outpace generic competition. The more longer-term product line extension

tactics, were no option: Lipitor! was already available in a great number of different dosages

(reformulation), a next generation Lipitor! increased, instead of decreased death rate [88] and its

combination drug Caduet! was –from a Pfizer perspective– a disappointment with annual sales

of just US$100 million [89]. New indications had already been investigated and patented during

Lipitor's! extensive clinical study program [90, p. 7]. The intended OTC status, though is the

right approach to serve a future US American health system, that will include more self-care

options in order to shift more –financial– responsibility to customers [61].

Q*(C-,':/#0-,(&,.(A/%$@4%($@-/9@$#(

Similar counter generic strategies have precedent, but Pfizer's scale and structure in manipulating

the market place has been unmatched [91,3]. Although it could minimize the impact of Lipitor's!

patent loss, none of the patent expiry strategies could save the firm from devastating results: A

profit decline by 14% in 2012 [92] forced Pfizer to downsize the company with layoffs as well as

spinoffs and to further cut R&D expenditures by 30% [93,94]: No company has nowadays the

capacity to fund the immense R&D expenses, while aggressively marketing its fading

8. Conclusion and further thoughts

27

blockbuster. Most counter generic strategies can buy time, but they cannot stop generic

competition [95]. The pharmaceutical industry undergoes a major transformation [96]. Given the

increasing payer dominance and an aging population, that requires more health care service, cost

pressure will continue to increase and further stimulate generic preference. The generic business

model eventually better fits current market conditions by addressing stakeholder needs more

effectively. The difficulties, Pfizer is facing are a lesson for the whole pharmaceutical industry.

Pfizer's business model is based on giant profits from Lipitor! and few other blockbusters drugs

–as most research-based companies [95]. The industry leader, created a totally profit driven

corporate culture, that allowed business units such as oncology to refuse remedies developed by

Pfizer scientists if management had doubts about their profitability [97]. Considering the

significant imbalance between new drug introduction and the sheer number of blockbusters

losing patent protection, times when Big Pharma could be arrogant enough to reject R&D

projects that would may not be profitable enough have passed [98]. Most of the big chronic

therapeutic classes with enormous sales potential have been harvested and are now well served

by inexpensive generics [99]. Yet, the majority of the 30,000 known diseases is poorly treated

exemplifying significant unexploited market potential [10, p. 82]. The remaining 80% are too

complex or specific to be fully understood or targeted [100]. In order for those business

opportunities to be realized, Big Phrama needs to understand that much of its success in the

1990's was due to a close and effective R&D collaboration with universities and scientists, rather

than aggressive and sometimes unethical management practices, only pushing for the most

profitable opportunities [95]. Research-based companies will need to manage a larger product

portfolio consisting of several niche products that generate smaller, but guaranteed returns [101,

p. 28,40]. This will reduce volatility, spread risk and decrease the overdependence on fading

blockbusters. In late 2013, Pfizer made a step indicating that the company has learned its lesson:

Pfizer introduced a highly specialized lung cancer drug –Xalkori!– that only works with a very

small target group. Such a result 15 years ago would have stopped drug investigation [40]?!

Appendix

28

!<<4,.0H

!

+::/#$%&$0-,#((

!

Illustration 3: Three main stakeholder groups in the pharmaceutical industry [102, p. 14], US insurance

structure [21] and co-payment level [103].

Illustration 7: The US statin market the 1990's and Lipitor! pricing policy to explain market dynamics

[62].

Appendix

29

Illustration 9: " US retail price for 20mg monthly Lipitor® supply [63, p. 4f.].

Appendix

30

R:-##&%;(

!

7-3'89#&4#' The world's biggest research-based pharmaceutical companies.

Blockbuster' A drug with annual global sales exceeding US$ 1 billion.

Hatch Waxman Act' A series of laws implemented in the US in 1984 to balance the

conflicting interests of generic and branded drug manufactures.!

:$%-+#"-)$' The medical term for a disease, condition or disorder that makes a

particular treatment advisable. For instance, high cholesterol is an

indication for statins.!

Molecule market' The market of a single chemical molecule intended to treat a

disease, such as atorvastatin or simvastatin. Before the patent for the

chemical molecule expires, the molecule market is 100% owned by

the branded drug. Several chemical compounds make up a drug

class, such as statins. Several drug classes can be found effective to

treat a disease (e.g. high cholesterol) and are referred to as

therapeutic class.

Off-label: ' The legal usage of a drug in way unapproved by the FDA such as

the case with age, dosage, formulation or indication: Sometimes, the

drug works for another, but unspecified condition, which is why a

physician might prescribe the drug for the unapproved indication.!

!

!

References

31

!"#"$"%&"'

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