Born Under a Cloud
According to 2004 American Heart Association (AHA) estimates, cardiovascular disease afflicts 78 million Americans (half 65
or over), and is responsible for 58 percent of all deaths. With those numbers, statins were predictably hailed as wonder drugs
by doctors and a license to print money by Wall Street. Public-health officials even joked about putting statins in the water,
The first statins quickly revealed two key side effects in a small percentage of patients: kidney problems and muscle damage.
Although the class has proved to be well tolerated by many millions of patients, in 2001 Bayer's statin, Baycol, was yanked
from the market following 31 deaths. Sales dropped for the four other statins on the market.
Such was the climate when rosuvastatin came before FDA with data showing it lowered LDL cholesterol and raised HDL further
and faster than its rivals. But higher potency often meant higher toxicity, and the agency demanded more safety tests. Approval
was finally granted in July 2003.
With its top-selling drug, Prilosec, losing its $6 billion annual sales to generics, AZ craved a seat on the statin gravy
train. But just as the statin marketing battle was heating up, the Vioxx scandal broke, fomenting near panic about drug safety.
The cloud over Crestor took on a toxic hue.
Yet the safety albatross that stymied Crestor's early growth was not simply a matter of bad timing, says Stan Bernard, MD,
MBA, of Bernard Associates. "Pfizer recognized that Crestor's superior potency was a threat to Lipitor, so the company—skillfully
and stealthily—refocused the statin discussion from efficacy to toxicity," he recalls. Even before Crestor was launched,
it had been positioned as a niche product too dangerous for ordinary use.
The British medical journal The Lancet slammed AZ for running its marketing machine "too hard and too fast" given the safety issues, and Sidney Wolfe, MD, of the
consumer group Public Citizen petitioned FDA to withdraw Crestor from the market. Then, at a now-legendary appearance before
a Senate hearing on Vioxx and drug safety, FDA researcher David Graham included Crestor on a list of five drugs he wanted
off the market. With sales plummeting, AstraZeneca ran full-page newspaper ads, defending Crestor, and TV spots claiming it
showed superiority over other statins, but the bad press persisted when FDA slammed the ads as misleading. Crestor sales were
$908 million in 2004, compared to market leader Lipitor's $10 billion and Zocor's $4 billion.
The cloud began to lift only when the results of one of the largest ever post-marketing studies of statins showed that all
four marketed statins were safe. Its reputation tattered but intact, Crestor took its place as statin of choice for patients
at highest risk of heart disease. As the most powerful statin arriving late to the party, Crestor presented a challenge: How
to strengthen its claim to superiority so it could withstand the class effect when Merck's Zocor went generic in 2006.