Heartbreak at the Cardio Confab

April 4, 2007

Pharmaceutical Executive

Volume 0, Issue 0

Promising drugs failed to deliver at this year's American College of Cardiology meeting.

A year of disappointments is one way to characterize the take-home message from last week's annual meeting of the American College of Cardiology, where negative drug data stole the show from nicer news.

Pfizer?s torcetrapib was the drug on everyone's mind, as the company was due to present what amounted to final autopsy results on its fallen cholesterol fighter. Ultrasounds and (real) autopsies showed that even though the CETP-inhibitor did raise HDL levels, it had no effect on atherosclerotic plaque--raising questions about whether all this extra "good cholesterol" in the blood makes any difference in preventing heart attacks and strokes.

"The substantial increase in HDL along with no significant regression in atherosclerosis was a novel finding," said Marcus Bain, an analyst at Decision Resources, adding that the data leaves researchers in the dark about whether the entire class of anti-CETP compounds will suffer from a similar all-bark, no-bite complex. Companies like Roche and Merck are staking their cardio-category futures on these drugs, and it could take several years before a verdict is reached.

AstraZeneca and partner AtheroGenics also received a gloomy prognosis for their frontrunner, AGI-1067--part of a new drug class to reduce atherosclerotic-plaque. The drug did not hit its primary Phase III endpoint: reducing cardiac events compared to a placebo.

But executives tried to buoy enthusiasm for some of the other findings, such as a decrease in the number of new diabetes cases and a decrease in cardiac death. "We believe this is certainly encouraging data," said AtheroGenics president and CEO Russell Medford, adding that the tiny biotech plans to continue development of the anti-inflammatory that as recently as December was being hailed for its "billion-dollar blockbuster potential" by Zack's Investment Research. Now Zack's is predicting that AstraZeneca will sever ties with AtheroGenics within 45 days.

Mary Argent-Katwala, an analyst at Decision Resources, is also skeptical that the clinical program can survive. "Unless they meet their primary endpoint, most doctors aren?t interested," she said.

The cardiovascular market, like the hypertension market, is entering its golden years, with cutthroat competition and an arsenal of reliable generics for doctors to try. Combination products have become trendy projects for companies in this crowded space. Merck and Schering-Plough, for instance, announced that they would be combining Zetia (ezetimibe) with atorvastatin (generic Lipitor). "In a lot of cases, it's about brand and lifecycle management," Argent-Katwala said.

Still, companies are searching for a new frontier--hence, the efforts to reduce inflammation and atherosclerotic plaque, however halting and unsteady. "That's the most active area of interest, and it's still an area that's not well understood," said Argent-Katwala.

On the brighter side, several small companies managed to shine at the high-profile confab. Isis is developing a compound (ISIS 301012) that can lower cholesterol an additional 50 percent when combined with a statin. "Those results are amazing," Argent-Katwala said. "We're predicting blockbuster status."

Bain was impressed by an ApoA-1 infusion product from Australia-based CSL Ltd. Studies have shown that people with higher levels of ApoA-1 Milano--a naturally occurring mutated strain of HDL protein discovered by accident and traced to a man in a village in northern Italy-- have a lower risk of heart disease, regardless of actual HDL levels. Although there are concerns about liver problems, investigators believe that the formulation of the drug--not the drug itself--might be to blame.