HOLDING

1 Pfizer2 GlaxoSmithKline3 Sanofi-Aventis4 Novartis5 AstraZeneca6 Johnson & Johnson7 Merck 8 Roche9 Lilly10 Wyeth

11 Bristol-Myers Squibb12 Amgen13 Abbott14 Boehringer-Ingelheim15 Bayer16 Takeda 17 Schering-Plough18 Teva19 Genentech20 Schering AG

21 Astellas Pharma22 Novo Nordisk23 Merck KGaA24 Eisai25 Otsuka26 Baxter27 Solvay28 Altana29 UCB30 Forest

31 Chugai32 Allergan33 Genzyme34 Gilead Sciences35 Serono36 Akzo Nobel37 Alcon38 CSL 39 King Pharmaceuticals40 Watson

41 Biogen Idec42 Mitsubishi Pharma43 Cephalon 44 Lundbeck45 Dainippon Sumitomo 46 Shire47 Nycomed Pharma48 Shionogi Seiyaku49 Actavis50 Tanabe Seiyaku

The industry experienced solid growth in 2006, but the realaction was among the midsize companies.That leaves us wondering: How long can Big Pharma hold on to its turf? BY PHARM EXEC STAFF

THE PHARM EXEC 50

PATTERN

Pfizer, Pfizer, Pfizer. Depending on yourpoint of view, it’s ironic, inspiring, ormerely interesting that the company that

staggered out of 2006 with its every vulnerabil-ity and vanity exposed in the media glarenonetheless finishes in Pharm Exec’s winner’scircle for the eighth year running.

A rat-a-tat of patent expirations on big-ticket products and big-time blowouts in itslate-stage pipeline have made Pfizer Exhibit Ain the growing case against the industry’sblockbuster model, yet the drug juggernautstill raked in $45.08 billion in sales. That putsthe feisty firm solidly ahead of its closest com-petitors: GlaxoSmithKline, with $39.21 bil-lion, and Sanofi-Aventis, with $37.43 billion.The number that may be keeping new PfizerCEO Jeffrey Kindler up at night, though, is thecompany’s 2 percent growth in sales—a far cryfrom GSK’s 15 percent, Sanofi’s 16 percent,and the 18 percent scored by Novartis.

In fact, for all the doom-and-gloom inkspilled about pharma’s fortunes, the industryperformed surprising well, with $643 billion inglobal sales. And, thanks mainly to MedicarePart D success, prescription revenues in theUnited States rose by 8.3 percent.

As for company rankings, the keyword wasstability, with Pfizer, GSK, Sanofi-Aventis, Novar-tis, AstraZeneca, J&J, and Merck all topping thecharts for the fourth year, while Wyeth, Roche,Lilly, and Bristol-Myers Squibb juggled placesjust below. Roche grew 31 percent to nearly $17billion, jumping from 12th to eighth—without

counting revenue from its majority stake inGenentech. Equally notable was BMS’s fall fromgrace, down 9 percent in sales and out of the Top10 for the first time since this ranking began—thanks to the at-risk launch of generic Plavix andpatent expiry on Pravachol.

Still, there was evidence that the global mar-ket remains in the grip of trends that BigPharma has yet to master. As IMS analyst Mur-ray Aitken says, “We continue to see a shift ingrowth away from mature markets to emergingones, and from primary care classes to biotechand specialist-driven therapies.” In 2006, spe-cialty drugs contributed 62 percent of totalgrowth—a giant jump from its 2000 delivery of35 percent. The top news of our Top 50 maywell be the success of the specialty firms.Cephalon, for example, makes its Top 50 debut,and Gilead, led by sales of Truvada, recorded43 percent growth. In 2006, Nycomed Pharmaalso made the Top 50 list. Watch for additionalgrowth next year: In December 2006, the com-pany snatched up German pharma Altana, acompany almost twice its size.

At the same time, generics companies con-tinued to benefit from the worldwide focus oncost cutting. Iceland-based Actavis recorded awhopping 219 percent growth, while Teva—buoyed by its six-month exclusivity on genericZocor and Zoloft—grew 65 percent.

With these dynamics, 2007 is shaping up as adecisive year. As the competition between largeand midsize pharmas boils over, we can onlywonder how long this stability will last.

The number thatmay be keepingnew Pfizer CEOJeffrey Kindler upat night is the 2 percent growth in sales—a far cryfrom GSK’s 15 percent, Sanofi’s16 percent, and the18 percent growthscored by Novartis

SOME NOTES ON THE LISTFigures in virtually all cases are based on numbersfound in companies’ annual reports or SEC filings.Companies are ranked by their human prescriptiondrug sales.To the extent possible, we include prescription generics and vaccines.We excludeover-the-counter products, royalty income, animal-health products, sales of bulk pharmaceuticals andactive pharmaceutical ingredients, and revenuefrom contract manufacturing.This is a less-than-perfect process, since some companies break outtheir sales figures in other ways and because somemajor products are sold as Rx and OTC products indifferent countries.There are handful of companiesthat may belong on the list but for which we havenever been able to obtain reliable numbers. Most ofthem are privately held, like Menarini. Procter &Gamble probably also belongs on the list, but bypolicy it declines to divulge revenue figures for itspharmaceutical unit.When necessary, we have converted foreign currencies to US dollars.The percentage growth figure is calculated based on US dollars. Because of changing currency exchangerates, this calculation exaggerates the growth ofmany European companies.

A SpecialReport on theWorld’s Top 50

PharmaCompanies

PHARMACEUTICAL EXECUTIVE 99

Key Insights on the Top10 Merck » Slashes price of Zocor afterLDL-lowerer goes off-patent. » Self-com-missioned Martin Report absolves man-agers of any wrongdoing related to Vioxxmarketing. » DTC ads for HPV vaccineGardasil garner praise, but mandatoryvaccination push draws criticism. »Beats Novartis to market with first-in-class diabetes drug Januvia, a DPP-4inhibitor. » Admits to developing a CETP-inhibitor in the same class as failedtorcetrapib. » Acquires biotech SirnaTherapeutics to develop RNAi therapies.» Partners with Schering-Plough onZetia/atorvastatin combo pill.

GlaxoSmithKline » TestsHPV vaccine Cervarix head-to-head against Merck’s Gardasil. » Cuts marketing budget, con-solidating professional advertis-ing under one holding company.» Submits oral breast cancerdrug Tykerb for FDA approvalafter promising results. »Launches first-line diabetestreatment Avandamet.

PHARMACEUTICAL EXECUTIVE100 MAY 2007 www.pharmexec.com

Rank Company & Headquarters 2006 Global Pharma R&D 2006 Top-[’05 Rank] [Web site] Sales [change from 2005] Spend Selling Drugs [2006 sales]

1 [1]

Pfizer $45.08 B [2%] $7,599 MNew York, NY [pfizer.com]

2 [2]

GlaxoSmithKline $39.21 B [15%] $6,549 MLondon, England [gsk.com]

3 [3]

Sanofi-Aventis $37.43 [16%] $5,844 MParis, France [sanofi-aventis.com]

4 [4]

Novartis $29.49 B [18%] $5,474 MBasel, Switzerland [novartis.com]

5 [5]

AstraZeneca $26.48 B [11%] $3,902 MLondon, England [astrazeneca.com]

6 [6]

Johnson & Johnson $23.27 B [4%] $5,000 MNew Brunswick, NJ [jnj.com]

7[7]

Merck $22.64 B [3%] $4,783 MWhitehouse Station, NJ [merck.com]

8 [12]

Roche $16.86 B [31%] $2,695 MBasel, Switzerland [roche.com]

9 [10]

Lilly $15.69 B [7%] $3,129 MIndianapolis, IN [lilly.com]

10 [8]

Wyeth $15.68 B [10%] $2,896 MMadison, NJ [wyeth.com]

Wyeth » HRTsales rebounddespite cancer,cardio concerns. »365-day contracep-tive Lybrel gets FDAapprovable letter.

J&J » AcquiresPfizer’s consumerbrands. » Defendsagainst lawsuitscharging that birthcontrol patch OrthoEvra raises clot risk.

AstraZeneca »Partners withAbbott on choles-terol drug combin-ing a fibrate withCrestor. » Hit bylate-phase set-backs on productslike Galida, Exanta,and a stroke drug. » PurchasesCambridge AntibodyTechnology.

Pfizer » In July, Jeff Kindler steps up asCEO, replacing Hank McKinnell. » PhaseIII results show that HDL-booster torce-trapib plus Lipitor causes more deathsthan Lipitor alone. » Restructures opera-tions into five business units and trims10 percent of its workforce. » Cuts 20percent of its sales force while pledgingto ramp up communication with payersand patients. » Launches new consumercampaigns for products such as Lipitor,Celebrex, Chantix, and Caduet. » Sellsconsumer business to J&J to becomepure-play pharma company. » Launches,and then relaunches, inhaled insulin prod-uct Exubera.

Sanofi-Aventis» FDA furtherdelays decision onAcomplia. » Headsto court to defendPlavix patent. »Updates safetydata on both Ketekand Ambien labels.

Lilly » NY Timesaccuses companyof inappropriatelymarketing Zyprexa.» Acquires Cialispartner Icos. » Inksdiabetic retinopa-thy deal with Alcon.

Roche » Startsshopping spree tolicense or acquirebiotech products. »Defends Tamifluafter fears raisedabout side effects,drug shortages.

Novartis » Completes acquisition of biotech Chiron,building strength in vaccines. » Launches two new drugs forhypertension, Exforge andTekturna. » Faces setbackwhen FDA requests moresafety data on DPP-4 inhibitorGalvus. » Reaches agreementto sell medical nutrition unit,including Gerber, to Nestle. »Gleevec gets broader label.

Lipitor $12.89 BNorvasc $4.87 BZoloft $2.11 B

Seretide/Advair $6.47 BAvandia/Avandament $3.22 BLamictal $1.95 B

Lovenox $3.21 BPlavix $2.94 BStilnox/Ambien/Ambien CR $2.67 B

Diovan $4.22 BGleevec/Glivec $2.55 BLotrel $1.35 B

Nexium $5.18 BSeroquel $3.42 BCrestor $2.03 B

Risperdal $4.18 BEprex/Procrit $3.18 BRemicade $3.01 B

Singulair $3.58 BCozaar/Hyzaar $3.16 BFosamax $3.13 B

MabThera/Rituxan $3.95 BHerceptin $3.20 BAvastin $2.42 B

Zyprexa $4.36 BGemzar $1.41 BCymbalta $1.32 B

Effexor $3.72 BPrevnar $1.96 BProtonix $1.80 B

Aranesp wasAra

UPUP 4444%%in 2006

TOP 10 US PRODUCTS OF 2006 Product [Maker] 2006 Sales in billions Growth in Sales1. Lipitor [Pfizer] $8.6 3.6%2. Nexium [AstraZeneca] $5.1 18.6%3. Advair Diskus [GlaxoSmithKline] $3.9 11.4%4. Aranesp [Amgen] $3.9 44.4%5. Prevacid [TAP] $3.5 -7.9%6. Epogen [Amgen] $3.2 10.3%7. Zocor [Merck] $3.1 -29.5%8. Enbrel [Amgen/Wyeth] $3.0 11.1%9. Seroquel [AstraZeneca] $3.0 15.4%10. Singulair [Merck] $3.0 20%

TOP 10 GLOBAL PRODUCTS OF 2006 Product [Maker] 2006 Sales in billions Growth in Sales1. Lipitor [Pfizer] $13.6 4.2%2. Nexium [AstraZeneca] $6.7 16.9%3. Seretide/Advair [GlaxoSmithKline] $6.3 10.3%4. Plavix [Sanofi-Aventis/BMS] $5.8 -3.4%5. Norvasc [Pfizer] $5.0 -0.5%6. Aranesp [Amgen] $5.0 35.6%7. Zyprexa [Lilly] $4.7 -0.4%8. Risperdal [Janssen-Ortho] $4.6 12.3%9. Enbrel [Amgen/Wyeth] $4.5 18.4%10. Effexor [Wyeth] $4.0 2.7%

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A PharmExec Graphic

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PHARMACEUTICAL EXECUTIVE102 MAY 2007 www.pharmexec.com

Rank Company & Headquarters 2006 Global Pharma R&D 2006 Top-[’05 Rank] [Web site] Sales [change from 2005] Spend Selling Drugs [2006 sales]

11 [9]

Bristol-Myers Squibb $13.86 B [-9%] $3,067 M Plavix $3.25 BNew York, NY [bms.com]

12 [13]

Amgen $13.86 B [15%] $3,366 M Aranesp $4.12 BThousand Oaks, CA [amgen.com]

13 [11]

Abbott $12.40 B [-9%] $2,255 M Humira $2.04 BAbbott Park, IL [abbott.com]

14 [14]

Boehringer-Ingelheim $10.96 B [29%] $2,015 M Spiriva $1.82 BIngelheim, Germany [boehringer-ingelheim.com]

15 [18]

Bayer $9.87 B [105%] $1,881 M Kogenate $1.04 BLeverkusen, Germany [bayer.com]

16 [15]

Takeda $8.68 B [2%] $1,444 M Actos $.02 BOsaka, Japan [takeda.com]

17[17]

Schering-Plough $8.56 B [13%] $2,188 M Remicade $1.24 BKenilworth, NJ [sch-plough.com]

18 [23]

Teva $7.82 B [65%] $495 M Copaxone $1.41 BPetach, Tikva, Israel [tevapharm.com]

19 [20]

Genentech $7.64 B [39%] $1,773 M Rituxan $2.07 BSouth San Francisco, CA [gene.com]

20 [19]

Schering AG $7.48 B [19%] $3,520 M Betaferon $1.31 BBerlin, Germany [schering.de]

TOP 10 COMPANIES BY US SALESCompany Total Sales US billions 1. Pfizer $26.7 2. GlaxoSmithKline $21.73. Merck $16.54. Johnson & Johnson $16.0 5. AstraZeneca $14.66. Amgen $14.57. Novartis $13.88. Sanofi-Aventis $10.9 9. Roche $10.210. Lilly $9.2

TOP 10 MOVERS Company Total Sales US billions [Market Share]1. Actavis 219%2. Bayer 105%3. Nycomed Pharma 70%4. Teva 65%5. Cephalon 48%6. Dainippon Sumitomo 44%7. Gilead 43%8. Genentech 39%9. Roche 31%10. Boehringer-Ingelheim 29%

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[8.3%]AMOUNT SALES GREW IN THE US FOR 2006.TOTAL US SALES WERE

$274.8 BILLION, COMPARED WITH

$253.7 BILLION IN 2005

[31]THE NUMBER

OF NEW PRODUCTS THAT WERE LAUNCHED

IN 2006

With a growth rate of 20 percent in 2006, “biologics” is still the fastest-growing segment in the pharmaceutical market. It generated $40.3 billion in sales in 2006.

PHARMACEUTICAL EXECUTIVE106 MAY 2007 www.pharmexec.com

Rank Company & Headquarters 2006 Global Pharma R&D 2006 Top-[’05 Rank] [Web site] Sales [change from 2005] Spend Selling Drugs [2006 sales]

21 [16]

Astellas Pharma $7.09 B [-8%] $1,189 M Prograf $1.22 BTokyo, Japan [astellas.com]

22 [21]

Novo Nordisk $6.85 B [28%] $689 M Human Insulin $2.59 BBagsvaerd, Denmark [novonordisk.com]

23 [24]

Merck KGAA $4.91 B [6%] $797 M Concor family of products $0.46 BDarmstadt, Germany [merck.de]

24 [22]

Eisai $4.85 B [2%] $1,328 M Aricept $1.64 BTokyo, Japan [eisai.co.jp]

25 [26]

Otsuka $4.14 B [25%] $883 M Abilify N/ATokyo, Japan [otsuka.co.jp]

26 [29]

Baxter $3.88 B [28%] $614 M Advate $0.85 BDeerfield, IL [baxter.com]

27[33]

Solvay $3.43 B [28%] $559 M TriCor/Lipanthyl $0.54 BBrussels, Belgium [solvay.com]

28 [31]

Altana* $2.98 B [22%] $653 M Protonix $2.05 BBad Homburg,Germany [altana.com]

29 [34]

UCB $2.89 B [19%] $811 M Keppra $1.00 BBrussels, Belgium [ucb-group.com]

30 [27]

Forest $2.79 B [-9%] $410 M Lexapro $1.87 BNew York, NY [frx.com]

*Altana and Nycomed merged in December 2006, but we reported the numbers as if they completed the year independently.

SOURCE: IMS MIDAS, MAT December 2006*Excluding Japan47.7%

29.9%

9.3%

8.6%4.5%

GLOBAL PHARMACEUTICAL SALES BY REGION, 2006Percent of Global Sales Market 2006 Sales (US$B) % Growth from 2005 North America $289.9 8.0% Europe $181.8 4.8% Japan $56.7 -.07% Asia*, Africa, and Australia $52.0 9.8% Latin America $27.5 12.9%

[62]

[$43B]

The global pharmaceutical market grew by

7 percent to approximately

$643 billion,at constant exchange rates

THE COMBINED R&D INVESTMENT OF PhRMA MEMBERS IN 2006

PERCENT OF THE GROWTH IN THE MARKETPLACE

FUELED BY SPECIALIST-

DRIVEN PRODUCTS

A PharmExec Graphic

TOP 10 R&D SPENDCompany Total R&D Spend US billions 1. Pfizer $7.5992. GlaxoSmithKline $6.5493. Sanofi-Aventis $5.8444. Novartis $5.4745. Johnson & Johnson $5.06. Merck $4.7837. AstraZeneca $3.9028. Schering AG $3.5209. Amgen $3.36610. Lilly $3.129 S

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31 [32]

Chugai $2.73 B [-2%] $457 M Epogin $0.53 BTokyo, Japan [chugai-pharm.co.jp]

32 [37]

Allergan $2.64 B [16%] $476 M Botox $0.98 BIrvine, CA [allergan.com]

33 [35]

Genzyme $2.63 B [20%] $650 M Cerezyme $1.01 BCambridge, MA [genzyme.com]

34 [39]

Gilead Sciences $2.59 B [43%] $384 M Truvada $1.19 BFoster City, CA [gilead.com]

35 [36]

Serono $2.50 B [7%] $560 M Rebif $1.45 BGeneva [merckserono.net]

Rank Company & Headquarters 2006 Global Pharma R&D 2006 Top-[’05 Rank] [Web site] Sales [change from 2005] Spend Selling Drugs [2006 sales]

36 [30]

Akzo Nobel $2.24 B [22%] $639 M Puregon/Follistim $0.51 BArnhem, Netherlands [akzonobel.com]

37[40]

Alcon $2.01 B [14%] $292 M Glaucoma products $0.69 BHünenberg, Switzerland [alcon.com]

38 CSL $1.97 B [8%] $120 M Helixate $0.39 BVictoria, Australia [csl.com.au]

39 [46]

King Pharmaceutical $1.89 B [13%] $254 M Altace $0.65 BBristol, TN [kingpharm.com]

40 [42]

Watson $1.86 B [14%] $131 M Ferrlecit $0.13 BCorona, CA [watson.com]

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[22]PERCENT THAT VOLUME OF

PRESCRIPTION SALES ROSE

[6.5]

TOP THERAPEUTIC CLASSES BY US SALES Therapeutic Class 2006 Sales in Billions* Lipid regulators $21.6 Proton pump inhibitors $13.6 Antidepressants $13.5 Antipsychotics $11.5 Erythropoietins $10.0 Seizure disorders $8.9 Monoclonal antibodies $5.8 Angiotensin II antagonists $5.7 Insulin sensitizer $4.8 Calcium blockers $4.7 A PharmExec Graphic

ONCOLOGICS WAS THE FASTEST-GROWING CATEGORY, UP 20.5 PERCENT. ERBITUX, AVASTIN, RITUXAN, AND HERCEPTIN EMERGED AS WINNERS[2,075]

PERCENT THAT GLOBAL

SALES OF GENERICS GREW

IN 2006

THE NUMBER OF PRODUCTS IN

CLINICAL DEVELOPMENT GREW 7 PERCENT TO

*Represents prescription pharmaceuticalpurchases including insulin at wholesaleprices by retail, food stores and chains,mass merchandisers, independent pharmacies, mail services, non-federaland federal hospitals, clinics, closed-wallHMOs, long-term care pharmacies, homehealthcare, and prisons/universities.Excludes co-marketing agreements. Joint-ventures assigned to product owner.Data run by redesign to include completedmergers and acquisitions.

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Rank Company & Headquarters 2006 Global Pharma R&D 2006 Top-[’05 Rank] [Web site] Sales [change from 2005] Spend Selling Drugs [2006 sales]

41 [43]

Biogen Idec $1.78 B [10%] $718 MCambridge, MA [biogen.com]

Avonex $1.71 B

42 [38]

Mitsubishi Pharma $1.73 B [-9%] $408 M NA N/AOsaka, Japan [www.m-pharma.co.jp]

43 Cephalon $1.72 B [48%] $403 M Provigil $0.74 BFrazer, PA [cephalon.com]

44 [41]

Lundbeck $1.66 B [.3%] $351 M Cipralex $0.63 BCopenhagen, Denmark [lundbeck.com]

45 Dainippon Sumitomo $1.64 B [44%] $252 M Amiodin $0.48 BOsaka, Japan [ds-pharma.co.jp]

46 [44]

Shire $1.54 B [16%] $387 M Adderall XR $0.86 BHampshire, England [shire.com]

47 Nycomed Pharma* $1.50 B [70%] $49 M Calcichew $0.12 BLuxembourg [nycomed.com]

48 [45]

Shionogi Seiyaku $1.43 B [-9%] $0 M Flomox $0.29 BOsaka, Japan [shionogi.co.jp]

49 Actavis $1.40 B [219%] $88 M Gabapentin $0.06 BHafnarfjordur, Iceland [actavis.com]

50 [47]

Tanabe Seiyaku $1.35 B [-9%] $2 M Herbesser $0.16 BOsaka, Japan [tanabe.co.jp]

*Altana and Nycomed merged in December 2006, but we reported the numbers as if they completed the year independently.