It took 20 years, researchers on two continents, and the advent of DNA-cloning technology before the HPV–cervical cancer connection
was confirmed. Then in the early 1990s, a separate discovery showed that "empty virus cells" could be manufactured free of
HPV DNA encoding, and the path was paved for a preventative vaccine. In 1995, Merck licensed the technology to make the DNA-less
virus shells from Melbourne, Australia-based CSL Limited.
Eliav Barr, head of clinical development for Gardasil
The company would spend the next 11 years trying to prove that the concept worked. And it did, big time: 100 percent efficacy
for HPV types 16 and 18—which cause 70 percent of cervical cancer—as well as types 6 and 11, which cause genital warts.
Merck's clinical team first hit pay dirt in June 2001, when it got the results of a blinded interim analysis of Gardasil's
HPV-16 component. "It took my breath away," said Eliav Barr, MD, head of clinical development for Gardasil, in an interview
with Pharmaceutical Executive last May. "Vaccines tend to be much higher in terms of efficacy than drugs, but even there, there are few vaccines that are
100 percent efficacious: measles, mumps, rubella, and Merck's hepatitis A vaccine—but that's about it."
Playing 'To Win'
The story of Gardasil's development reads like a throwback to Merck's days as drug-industry golden boy. When the vaccine made
its debut on June 8, 2006 however, the company was anything but. In fact, the timing of its approval made it one of the first
products launched under Merck's new commercialization model, adopted six months earlier as part of a five-year cost-cutting
initiative. The model calls for strategic investments "to win" major product launches. It also meant that the Gardasil team
worked within a defined franchise structure, with marketing, regulatory, clinical, and policy staff reporting to franchise
vice president and general manager Bev Lybrand.
At December's analyst meeting, Peter Loescher, Merck's president of global human health, outlined four company objectives
for the vaccine's debut: support global policy recommendations, secure broad public and private funding, encourage strong
uptake among healthcare providers, and motivate women in the target age group (or their parents) to ask for the vaccine.
Although the goals covered four distinct areas, Merck couldn't begin to call Gardasil a success without first convincing policymakers—both
in government and professional medical groups—of its impact. To get the sort of broad coverage that it hoped for, Gardasil
would have to be integrated into a child's vaccine schedule, a recommended timetable set by the Centers for Disease Control
and Prevention (CDC). States and school districts then have the authority to make these vaccines mandatory. Physicians and
payers—both public and private—tend to yield to these guidelines.
"In the very beginning, I saw HPV predominantly as an education challenge," says Rick Haupt, MD, executive director of medical
affairs at Merck. A pediatrician and longtime Merck consultant, Haupt was asked in 2001 to start thinking about the policy
issues surrounding Gardasil—around the same time that researchers first realized that the efficacy studies with the vaccine
surpassed anything they could have hoped for. "What drives the standard of care for providers is what their professional society
recommends as well as the ACIP," says Haupt.