Hoping to impress investors last Thursday, the company was more open than ever before about its pipeline of future medicines. Pfizer executives and scientists entertained Wall Streeters with tales of its 242 research programs underway in 11 therapeutic areas like obesity, Alzheimer's, cancer, diabetes and HIV. "We have momentum, very aggressive targets and breakthrough science virtually across the board," said John LaMattina, president of Pfizer Global Research and Development.

A decade ago, unveiling one's pipeline to this degree of detail was considered suicide among Big Pharma CEOs. But over the last decade, as companies began churning out fewer drugs, they felt compelled to reveal more of their secret projects in order to whet investors' appetites for potential growth.

The problem with showing off all the whiz-bang lab work? Even with an annual research budget of $7.5 billion and an army of 13,000 scientists, the failure rate of experimental drugmaking at Pfizer has always been incredibly high.

It's the same at every big drugmaker. When Merck, for instance, started to reveal more and more of its research to the Street in the late '90s, it contributed to CEO Ray Gilmartin's ouster in 2005. The beginning of Gilmartin's end came a full year before Vioxx. In 2003, Merck scientists discontinued development on four potential blockbuster compounds in the latter stages of development. One of those medicines would have been Merck's first entrant into the lucrative antidepressant market.

With great expectations comes great disappointment; none of the four treatments actually made it to market. Investors punished Merck. The company's shares tumbled 25 percent over the next year - before the Vioxx debacle.

More importantly, Pfizer's biggest problem is that it's too big. In most other businesses, a $400 million-a-year product with 80 percent margins is a welcome addition to a company's bottom line. But for most Big Pharma companies, medicines don't really matter unless they have the potential to be blockbusters - generating annual revenues in the range of $1 to $2 billion. When you're a $52 billion (revenue) company like Pfizer, blockbusters are the only products that move the needle and demonstrate growth.

The need for blockbuster drugs is especially pronounced when other big sellers are losing patent protection. By the end of 2007, Pfizer will have endured three years of patent-protection losses on major drugs including blood pressure pill, Norvasc, antibiotic Zithromax, and anti-depressant Zoloft. That's another $14 billion in annual sales - gone.

That Pfizer has so much riding on torcetripib - a single drug whose sales could have outstripped the GDP of small countries like Iceland and Togo - underscores what ails the drug business.

The story of the Very Big, Big Pharma begins in the 1990s. Though consolidation had always been a fact of life among drugmakers, M&A activity became more brisk.

By the end of the decade, it wasn't the PhDs in lab coats who were embarking on the boldest experiments in medicine making - it was the MBAs. Executive suites teemed with visionary leaders who had concocted a new formula for success: getting huge. In 1999, Astra AB and Zeneca combined to form AstraZeneca. That same year, the merger of Hoeschst AG and Rhone-Poulenc created Aventis. In 2000, Pharmacia/Upjohn paired with Searle, Glaxo Welcome joined with SmithKline Beecham, and Pfizer took over Warner-Lambert after a dramatic bidding war. Two years later, Pfizer purchased Pharmacia. And Hank McKinnell, who orchestrated both of Pfizer's major acquisitions - first as CFO, then as the company's CEO - became the most vocal proponent of the new, large drug-company paradigm.

McKinnell had helped Pfizer leap from the world's 14th largest drug firm in the early 1990s to the top of the heap. He and others argued that economies of scale and synergies would allow companies to plow enormous resources into sales, marketing, distribution, and most importantly research and development of new medicines. The new model, McKinnell insisted, would usher in a new age of drug discovery.

"Size helps," McKinnell told Fortune in 2002. "Chemical suppliers return our calls faster, we can run very large-scale global clinical studies, and we can try out the newest technologies and implement them rapidly in order to do things others can't. So, there are real advantages to scale."

Today, Hank McKinnell is out of a job. Pfizer's board forced him into early retirement last July in large part because his vision for Big Pfizer has yet to pay off for investors. During McKinnell's tenure from January 2001 to July 28, 2006, Pfizer shares lost 38 percent of their value.

It's the same among other large companies in the industry. The spate of mergers has so far failed to enhance shareholder value. Yes, size does matter when it comes to sales, marketing, distribution and holding sway with regulators. But what's suffered most under the new paradigm is research. As companies became larger and their appetites for blockbusters grew, many companies began scuttling research projects that appear not to be instant blockbusters. This practice hurts morale, wastes R&D money, and is reducing the number of "successes" companies can point to.

Explains one Big Pharma research executive (who offered this insight on condition that Fortune withhold his name and company): "Often there are late-stage opportunities drop off because the money we put in won't get a good return. It's frustrating for scientists when they get something that looks good and they're told that because of what it would cost to develop this drug versus the potential size of its market, it's not an opportunity for us."

In the end, large drug companies have become less innovative for the same reasons big operations in any business aren't as innovative as their smaller, hungrier competitors. There are a host of reasons, notably that scientists in small companies are highly motivated by the potential big payoff a breakthrough can earn.

But regardless of the reasons, for large-cap pharma companies, the very means of generating new products is broken. As companies have grown larger, research operations are becoming less productive. The number of novel medicines the industry submits to the FDA has fallen from an annual average of 41 between 1995 and 2000, to 27 per year this decade. (That number would look worse if Big Pharma companies weren't buying or licensing-in an increasing number of test compounds from smaller drugmakers and biotech firms.)

Instead of buying innovative research, Pfizer and other big drugmakers need to pare down, balance their portfolios with small, medium and large-selling drugs, and find ways of replicating smaller, creative lab environments. Until then, we're in for a lot more financial disappointments like torcetripib.

Unternehmenschef Jeffrey B. Kindler gab erst kürzlich bekannt, dass sich der Umsatz in den kommenden zwei Jahren nur auf dem Niveau des laufenden Geschäftsjahres bewegen wird. Die Analysten von Lehman Brothers halten gar stagnierende Umsätze in den nächsten sieben Jahren für möglich.Einer der Hauptgründe ist die Konkurrenz von Nachahmerprodukten (Generika). Diese werden nach Patentablauf der Originale in Zeiten weltweit sinkender Gesundheitsbudgets vermehrt verschrieben. Gleichzeitig brachte Pfizer in den vergangenen Jahren keine neuen Mega-Seller auf den Markt.Hauptsächlich über Sparmaßnahmen soll es Pfizer dennoch ab 2007 auf ein jährliches Gewinnwachstum im hohen einstelligen Prozentbereich bringen.

"Die langfristige Perspektive hat sich durch das Aus für Torcetrapib deutlich eingetrübt", sagt Björn Wolber, Analyst von Independent Research. "In der Spitze sollte das Medikament bis zu 20 Milliarden Dollar Jahresumsatz bringen, die nun in der Langfristplanung wegfallen." Zum Vergleich: Im vergangenen Jahr setzte Pfizer insgesamt gut 50 Mrd. Dollar um. Dazu trug der ab 2011 der Billigkonkurrenz ausgesetzte Blockbuster Lipitor über ein Fünftel bei. Laut Wolber besteht das Problem darin, dass Pfizer kein ähnlich viel versprechendes Produkt in der Pipeline hat. "Das Unternehmen selbst gibt zu, dass organisches Wachstum mittelfristig kaum möglich ist", sagt Wolber.

Diesen Nachteil wird Pfizer auszugleichen versuchen. Die Analysten der Jyske Bank rechnen in einer Studie mit Übernahmen. Und auch Wolber sagt: "Pfizer wird Wachstum nun einkaufen." Der Geldbeutel jedenfalls ist voll. Nach Expertenschätzungen verfügt Pfizer über bis zu 50 Milliarden Dollar, die für Zukäufe verwendet werden können.

Aber auch aus eigener Kraft will Pfizer wieder wachsen. Die Analysten von Prudential Financial verweisen auf jährliche Ausgaben für Forschung und Entwicklung von über sieben Milliarden Dollar und gehen davon aus, dass das Unternehmen bei neuen Medikamenten "in Zukunft wieder mehr zu bieten"" habe.

Als Wette auf eine bessere Zukunft empfehlen einige Häuser – wie etwa Prudential – den Wert trotz der negativen Nachrichten der vergangenen Wochen zum Kauf. Prudential rechnet vor, dass das Kurs-Gewinn-Verhältnis (KGV) von Pfizer für 2006 und 2007 bei rund 13 beziehungsweise zwölf liegt. Im Vergleich mit anderen Unternehmen der Pharmaindustrie ist Pfizer damit sehr günstig bewertet.