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Pharm Exec's Pipeline Report 2011
The crowded cholesterol-control category is the biggest US drug market, with 2010 global sales close to $35 billion, according to IMS Health. A wide array of me-too statins, either generic or soon to be so, already excel at lowering LDL, or "bad" cholesterol, leaving the increase of HDL, or "good" cholesterol, the only low-hanging fruit left in this orchard. Many studies have confirmed that high levels of high-density lipoproteins, which collect the artery-blocking low-density kind and carry them to the liver for expulsion, correlate to low risk of atherosclerosis and heart attack. But in 2006, Pfizer's first-in-class CETP inhibitor flamed out in spectacular Phase III fashion because it increased not only HDL but patient deaths—by 60 percent—mostly due to hormone-induced hypertension.
Most CETP-inhibitor programs were promptly shuttered, but Merck, Roche, and smaller shops quietly persevered, tweaking their molecules to minimize the perceived risk. Last month, Merck snatched the spotlight at the annual heart-association confab with study data showing that patients on a statin and its CETP inhibitor, anacetrapib, had a 40 percent greater reduction in bad cholesterol than the statin-only group. Yet the 'wow' factor was that its good cholesterol soared by 140 percent, while blood pressure and cardiac problems were no different from placebo. Said Christopher Cannon, a cardiologist at Brigham & Women's Hospital and the study's lead researcher: "If what we are seeing now is borne out in larger studies, this could be the next big thing that could benefit hundreds of millions of people."
By contrast, Roche's Phase III anti-CETP contender, dalcetrapib, has demonstrated a weaker lipid punch, lifting HDL by 40 percent and lowering LDL by 15 percent. Other compounds are in the works to treat more serious disease.
Quantity is one thing, quality another. Some skeptics have raised doubts about how well—or even if—drug-produced HDL functions. Whether these high marks translate into clinical benefits—must wait until 2015 at the conclusion of Merck's $150 million, 30,000-person Phase III study. If they do, Merck may have a Lipitor-sized cash cow in its pasture.