It's potentially the most lucrative vaccine ever developed: An innovative inoculation that protects against the human papilloma virus (HPV), the main cause of cervical cancer—the second deadliest female cancer worldwide. And for Britain's GlaxoSmithKline (GSK), which on Mar. 29 submitted its Cervarix vaccine to the U.S. Food and Drug Administration for approval, it's also a major driver of future success, perhaps contributing up to one-third of sales and profit growth over the next five years.
But GSK, one of two companies targeting the market, almost missed its window of opportunity. Four years ago, GSK Bio, the British company's vaccine division based in Rixensart, Belgium, discovered it was more than two years behind archrival Merck (MRK), based in Whitehouse Station, N.J., which was also developing an HPV vaccine.
GSK realized that if it didn't find a way to close the gap fast, the battle for market share would be lost before it had begun. "We knew we had a major asset with our vaccine but if we didn't want to lose it, we had to accelerate the pace of development dramatically," says Dr. Philippe Monteyne, GSK Bio's vice-president of global vaccine development.
Under One Roof
So GSK borrowed a technique from the auto industry known as "one roof." France's Renault pioneered the technique: By plucking experts from various disciplines across the company and putting them "under one roof"—that is, full time on one project, in one location, reporting to a single leader—the carmaker was able to slash the development time of its compact car, the Twingo, by 18 months.
GSK Bio adopted a similar tactic and cut the development time of Cervarix in half. Instead of filing for approval at the end of 2008 as planned, "one roof" allowed GSK Bio to do it two-and-a-half years earlier than expected in Europe, and 18 months earlier in the U.S. If approved, as analysts expect it will be, Cervarix could be on the market in the U.S. within six months.
Convincing management to try the one roof approach wasn't easy, though. Development projects in the pharmaceutical industry often last more than a decade. Before switching to one roof, 80% of the people working on Cervarix spent only about 20% of their time on it. Instead of concentrating on the development of one vaccine at a time, researchers, marketing, and regulatory staff all oversaw numerous projects at various stages of development.
The question was, could a company with more than 20 vaccines under development afford to concentrate its resources and its talent on just one product? With its stake in a market—potentially worth $8 billion within three years—in jeopardy, GSK Bio decided to take the risk at the end of 2004. The aim of one roof, says Fabrice Enderlin, GSK Bio's vice-president of human resources, who suggested the plan, was to get employees "to live, dream, and sleep cervical cancer vaccine development."
Management hand-picked top people for the group—from research to marketing to regulatory affairs. In the course of a weekend, the new 80-person team was relocated from various offices across the Rixensart campus to one building with a central Cervarix "war room." Instead of scheduling formal meetings between departments, a process that used to take weeks, the Cervarix team held impromptu meetings in hallways or the cafeteria. The result: faster decision making. Instead of taking weeks, major decisions such as the design of clinical trials or the investment needed to scale up manufacturing were made the same day.
For Marie-Thérèse Martin, the project manager for Cervarix, the new strategy yielded other welcome changes. "With the old system, I was always working on three different projects at once," she says. "My biggest frustration was I always had competing priorities. But under one roof, there was no longer that stop-start distraction."
Major Leap of Faith
The new structure also made it easier for Martin to secure investment from management. Typically, vaccine companies run staggered clinical trials. They wait to see positive results before spending the money on expanding an existing trial or starting a new one. But with Cervarix, GSK didn't have the luxury of time. "We decided to increase the size of our clinical trials and run three different ones in parallel," Martin says.
At the same time, the one-roof team knew it had to scale up manufacturing of the vaccine even before the results of the clinical trials were known. This required a major leap of faith and a big injection of funds from management, which normally wants to see conclusive data before committing to further investment.
The one-roof team even managed to convince management to shell out $300 million to buy Seattle-based biotech Corixa. The startup made a molecule, known as an adjuvant, that boosted Cervarix's efficacy and the duration of its protection. GSK management signed off quickly on the acquisition in order to help cut the development time for Cervarix.
Closing the Gap
Still, the one-roof team recognized it couldn't afford to make any mistakes. To avoid problems created by going too fast, it set up detailed and more frequent project management checks. Instead of breaking the project into monthly goals, the one-roof group set daily objectives so corrective action could be taken immediately. "Now we look at every chain in the link continuously and act fast if we notice a problem," Martin says.
GSK reckons that even though Merck has a big head start, it should be able to close the gap quickly. Analysts agree, estimating that within five years Cervarix will generate sales of $2.4 billion, compared to $3.3 billion for Merck's vaccine, Gardasil, which was approved in the U.S. in June, 2006.
Both companies' vaccines target two strains of HPV that are responsible for 70% of all cervical cancers. Both vaccines have shown 100% efficacy in preventing these strains of HPV. Gardasil offers protection for five years and GSK for more than four-and-a-half years, although the latter plans to release additional clinical data in the coming weeks.
More and Better Protection
There are differences. Merck's vaccine also protects against HPV strains 6 and 11, which cause 90% of all genital warts. GSK's vaccine is purely focused on cancer-causing HPV. Thanks to its adjuvant system, Cervarix also offers protection against two other HPV strains, 45 and 31, which combined are responsible for another 10% of cervical cancers.
Together, these four strains of the virus account for 80% of all cervical cancer. Although these additional strains are not in the actual vaccine, the powerful adjuvant provides cross-protection against them anyway. The GSK adjuvant, says Beatrice Muzard, an analyst at Ixis Securities in Paris, "…speeds up the immune response, boosts efficacy, and extends immunity."
Moreover, by extending the cancer protection, the adjuvant enables GSK to market its vaccine purely on the basis of cancer prevention. Merck, by contrast, has also talked up Gardasil's ability to prevent against sexually transmitted disease. As a result, the company has run into backlash in the U.S. over calls to make the vaccine mandatory for girls as young as nine. Lawmakers in several states have considered ordering HPV vaccination, but efforts have stalled due to resistance from sexual abstinence advocates, parent groups, and religious and conservative organizations.
Head to Head Trials
Some analysts reckon that latecomer Cervarix may have significant advantages against Gardasil. These include better protection against more viral strains of HPV, better protection in women up to 55 years (Gardasil only works in women up to the age of 25), and potential long-term protection well beyond the standard five years, says Navid Malik, a pharmaceuticals analyst at London-based brokerage Collins Stewart.
So confident is GSK Bio of Cervarix's efficacy that the company is doing something unheard of in the vaccine business: Conducting head to head clinical trials comparing it to Gardasil. The results are expected next year. "Our vaccine is not just the second one to market," Monteyne says. "It is increasingly seen as the next-generation vaccine for cervical cancer." They can thank one roof for that.