said Monday that a final data analysis backs up a previous finding that its heart drug AGI-1067 is removing plaque from clogged arteries. But shares of the drugmaker fell, in part, because the amount of arterial plaque reduction was lower than expected.
AtheroGenics shares were down $4.74, or 15%, in recent trading.
AGI-1067 is a pill that aims to reduce the level of fatty plaque deposits (artherosclerosis) in a person's arteries, thereby lowering the risk of heart attack. The potential market for such a drug is enormous, considering that cholesterol-lowering statin drugs like
Lipitor (the world's top-selling drug with more than $10 billion in annual sales) only slow or halt the progression of heart disease. At best, Lipitor reduces plaque volume by a very small amount. AtheroGenics believes that AGI-1067 will have a much more significant impact on arterial plaque, and in a shorter period of time.
But AGI-1067 has been dogged by controversy ever since AtheroGenics released
interim results from a phase II study known as CART 2 in late September. While AtheroGenics claimed that the interim analysis was positive, critics charged the company with manipulating results in the drug's favor. It was hoped that final data from the CART 2 study would settle the argument.
Data Are Final, but There's More Debate
Monday, those final CART 2 study results were made public, but it doesn't appear as if the controversy over AGI-1067 will subside any time soon.
AtheroGenics said that AGI-1067 was able to reduce the level of arterial plaque by an average of 2.3% over 12 months, a statistically significant amount when compared with the patients' own baseline measurements. Patients in the placebo arm of the study saw only 0.8% reduction in their plaque levels from baseline.
While patients taking AGI-1067 did better than patients in the placebo arm of the study, the relative benefit between the two groups was not statistically significant, AtheroGenics said.
Furthermore, the data from the final analysis were worse than what was reported previously. In the interim analysis, conducted on fewer patients, AGI-1067 produced a 3.8% reduction in arterial plaque.
AtheroGenics said that treatment with AGI-1067 also produced a statistically significant reduction in levels of myeloperoxidase (MPO), an inflammatory biomarker that correlates with future cardiovascular events. High levels of MPO have been linked to increased risk of heart attack, the company said.
But the company did not present any data linking AGI-1067 to reductions in C-reactive protein, a much more widely recognized clinical biomarker for inflammation and cardiovascular risk.
As with the interim analysis, the final analysis was conducted at two leading hospitals -- Montreal Heart Institute and the Cleveland Clinic. The confirmatory analysis conducted by the Cleveland Clinic, not prespecified in the study's protocol, was one of the reasons some critics felt the AGI-10687 data were misleading, especially because doctors at Cleveland Clinic eliminated some patients from the study because their arterial scans were not readable.
In September, Dr. Steven Nissen of the Cleveland Clinic defended his role in analyzing AGI-1067, calling the drug promising if data could be verified in a late-stage study. But Dr. Eric Topol, another leading cardiologist from the Cleveland Clinic, criticized AtheroGenics and the way CART 2 data were analyzed.
There was no comment Monday from Nissen in AtheroGenics' press release and he was missing from the company's conference call. But Dr. Jean Claude Tardif of Montreal Heart, the lead investigator in the CART 2 study, was supportive.
"Given the regression signal in the AGI-1067 group, as well as the drug's ability to reduce myeloperoxidase, a biomarker closely associated with major adverse cardiac events, I believe we have enhanced our chances of seeing positive results in the phase III ARISE trial," he said.
AtheroGenics is already conducting a phase III study of AGI-1067, dubbed ARISE, which strives to show that the drug's ability to reduce plaque volume will lead to a real-world benefit for patients, measured by a reduction in cardiac-related illness such as heart attack. Investors have been so keyed on the CART 2 study because it was thought that positive data raised the odds that ARISE also will be successful. If ARISE is positive, AGI-1067 likely will be approved and stands a good chance of becoming the next blockbuster heart disease drug with multibillion-dollar sales potential.
Last December, Pfizer purchased Esperion Therapeutics for $1.3 billion in order to acquire that company's experimental plaque-busting heart drug. If AGI-1067 turns out to be just as good or better, Big Pharma likely will beat down AtheroGenics' door to acquire the company.
Adam Feuerstein writes regularly for RealMoney.com. In keeping with TSC's editorial policy, he doesn't own or short individual stocks, although he owns stock in TheStreet.com. He also doesn't invest in hedge funds or other private investment partnerships. He invites you to send your feedback to