The Pharm Exec Pipeline Report 2007 - Pharmaceutical Executive


The Pharm Exec Pipeline Report 2007

Pharmaceutical Executive

"Back on the Horse"
HDL Cholesterol: Torcetrapib Redux

Pfizer spent $1 billion to develop the CTEP inhibitor torcetrapib, a drug that aimed to raise levels of HDL ("good") cholesterol, then pulled the plug when studies showed that patients on a combination of Lipitor and torcetrapib were 25 percent more likely to die than patients on Lipitor alone. Now Roche and Merck are hoping that their own CETP inhibitors—drugs that block cholesterol ester transfer proteins and prevent the transformation of good HDL into bad LDL cholesterol—will not have the Pfizer drug's fatal flaw.

"The question that remains is whether it was a class effect or an effect specific to Pfizer's particular compound," said Donny Wong, a senior analyst at Decision Resources. "Merck claims that its drug [anacetrapib] doesn't raise blood pressure. And Roche claims that its drug [dalcetrapib] operates by a different mechanism of action from torcetrapib."

After seeing torcetrapib's final data at the American Heart Association in November, Steven Nissen, MD, head of cardiology at the Cleveland Clinic in Ohio, concluded that HDL drugs are viable. "We can get back on the horse and try again," he told Bloomberg News. Merck and Roche are expected to announce this month whether their programs will go forward.

Beyond Interferon
Hepatitis C: Targeting Nonresponders

Compared with AIDS, hepatitis C is a "raging, less-known epidemic," says John Lebbos, MD, director of infectious diseases at Decision Resources. Interferon is the standard of care, but it works only about half the time. Drugmakers face a patient population with advanced cases, many undiagnosed, most with progressive liver damage, including fibrosis and cirrhosis.

The most hotly anticipated new drugs are boceprevir and teleprevir, both protease inhibitors, which have yet to be differentiated by clinical data. "Physicians told us that what's most important is an increase in efficacy," says Lebbos. The first to market with a more effective drug will have first shot at the huge patient population of "nonresponders." In the long term, the differentiating factors will be sustained virological response (SVR) and resistance profile.

"It's not like HIV, where you might have an inherently resistant strain," Lebbos says. "The drugs are helping the body mount an immune response. If one protease inhibitor is less prone to resistant response, we will probably just see a higher proportion of patients responsive to it."

Albuferon is an incremental improvement over pegylated interferon. It may not be superior except for dosing and related quality-of-life issues, but that may be enough to win market share. "We see Albuferon exceeding $2 billion in sales if it pans out," Lebbos says.

Interferon is often administered with ribavirin, a somewhat nonspecific antiviral. Taribavirin is a ribavirin analogue, a new formulation to minimize side effects like anemia. The question there is efficacy: Noninferiority and safety may not be enough for an adjuntive therapy in the Hep C market, where physicians are keen on efficacy improvements.


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