'The Fabric of Discovery'

How Pfizer plans to meet its goal of 20 major new drug applications over five years. 

By Malorye A. Branca

In an exclusive 10-part online series, senior editor Malorye A. Branca explores the impact of genomic technologies on the pipelines and strategies of the world's 10 leading big pharmas, based on interviews with senior executives at each company. Here we extract from Part I — Pfizer. The full series can be found at www.bio-itworld.com/news/harvest.html.

March 17, 2004 | Like a seasoned poker player, Pfizer rarely telegraphs its moves. And since it announced the acquisition of rival Pharmacia last year, many pundits have been wondering exactly how the "even bigger" Pfizer will sustain profits. Its top competitors are expected to sweat simply producing the one to three products per year required to appease investors. By most accounts, Pfizer needs about twice that number. The company's own goal is "20 major new drug applications [NDAs] over five years, ending in 2006," according to CFO David Shedlarz. Six of those NDAs are already filed, with just 14 more to go.

So what role does genomics play in the Pfizer pipeline? Not surprisingly, Pfizer's strategy is to "leverage scale," says Philip Vickers, executive director of genomic and proteomic sciences at Pfizer Global Research and Development. It has plenty to work with. The company spent $7.1 billion on R&D last year alone, and claims to have "the industry's largest pharmaceutical R&D organization," according to its Web site: approximately 13,000 scientists spread across six major international research sites, working on 300 discovery projects, with a further 160 projects under development.

Genomics has become "part of the very fabric of discovery," Vickers says. There are genomics teams at each main site, but these groups have strong links with the therapeutic areas. Work with a high-infrastructure cost is centralized and becomes a global resource.

Like many of its competitors, Pfizer is bent on reducing the number of projects that fail late in the game, wasting huge investments. So that's where many of its tools, including genomics, are focused. It's a bit of a twist, since genomics was initially hailed as a gateway to better new drug targets. "We have done new-target hunting with genomics, and those studies are quite difficult," Vickers says. At Pfizer, gene hunting is now reserved for cases where "the underlying disease mechanisms are badly understood, and there is significant medical need."


Downstream Effect 
Instead, genomics is becoming more important downstream, helping the company select better compounds against its targets. For example, Pfizer is collecting DNA expression profiles from drug-treated cells. Profile patterns that signal specific effects, including toxic reactions, can help medicinal chemists design better drugs more quickly. "We want to uncover structure-activity relationships with great value across all of our portfolio, or look at particular areas of great interest," Vickers says, "rather than trying to do everything."

The full series can be found at www.bio-itworld.com/news/harvest.html. The companies and executives profiled are: AstraZeneca: Jan Lundberg, Executive Vice President, Global Drug Discovery, Aventis: Donald Anderson, Global Head, Pharmacogenomics and Clinical Affairs Bristol-Myers Squibb: Mark Cockett, Vice President, Applied Genomics Eli Lilly: Michael Clayman, Vice President, Science and Technology Administration GlaxoSmithKline: Allen D. Roses, Senior Vice President, Genetics Research Johnson & Johnson: Harlan Weisman, President, and Michael Jackson, Senior Vice President, Drug Discovery Merck: Stephen Friend, Senior Vice President, Molecular Profiling Novartis AG: Paul Herrling, Head of Corporate Research Pfizer: Philip Vickers, Executive Director, Genomic and Proteomic Sciences Wyeth Pharmaceuticals: Charlie Richard, Vice President, Genomics

Pfizer scientists are also tracking variations in genes such as CYP2D6, which helps control how the body processes drugs. "If you understand the variants, you may be able to predict how certain types of people will metabolize a drug," Vickers says. The company enrolls thousands of patients in clinical trials each year. Blood samples are stored, possibly for future studies of how genetic variation influences drug response (see "Pfizer Hopes to Link Patients, Pills," Sept. 2002 Bio·IT World, page 22).

When it comes to deals, Pfizer leaves little to chance, blanketing all the options and making offers that are tough to refuse. The company recently announced a $50-million deal with antibody company MorphoSys, one of the biotech's largest-ever deals. Pfizer also has a deal with MorphoSys' major competitor, Cambridge Antibody Technology. In the past few years, Pfizer has signed at least three deals with Affymetrix spinoff Perlegen, which is doing systematic genomewide SNP (single nucleotide polymorphism) screens. Pfizer has dozens of partners, and inherited more deals through its acquisition of Pharmacia (see www.bio-itworld.com/news/table.html).

Having such deep pockets gives Pfizer great freedom. Amortized over 20 years, the $1.3-billion Pfizer's recent bid for Esperion Therapeutics lowers the pharma titan's earnings per share by less than a cent, according to Goldman Sachs analyst James Kelly. Esperion is developing drugs aimed at removing plaque from arteries, including one popularly referred to as the "arterial Drano."

With its annual revenue more than $45 billion in 2003 and the Pharmacia acquisition in its rearview mirror, Pfizer will be buckling down to finish filing those 14 outstanding NDAs. One reason cited for the company's success is its savvy marketing and an army of 10,000 sales reps. But Pfizer remains committed to cutting-edge research, which it will need to meet its aggressive goals.

When he surveys the company's research labs, Vickers says that increasingly, "I can't tease genomics apart from our other discovery efforts." The applications for genomics are steadily expanding, he says: "For finding biomarkers, doing pharmacogenomics, and increasing our confidence in cell-based assays and animal models ... every project is touched in some way by it."