[There is no direct connection between OSCAR and AGIX’s controversial trial for AGI-1067, which was severely criticized by Dr. Topol of the Cleveland Clinic (#msg-4202972).). (A Reuters newswire this morning erroneously implied that Topol’s comments had something to do with OSCAR.)]
>> AtheroGenics Announces that OSCAR Phase II Study in Rheumatoid Arthritis Did Not Meet Primary Endpoint
ATLANTA, Oct. 13 /PRNewswire-FirstCall/ -- AtheroGenics, Inc. (Nasdaq: AGIX - News), a pharmaceutical company focused on the treatment of chronic inflammatory diseases, today released results of its OSCAR Phase II clinical trial studying AGIX-4207 in patients with rheumatoid arthritis. The results indicated that none of the three dosing arms of AGIX-4207 showed a statistically significant improvement in ACR 20 scores when compared to placebo, the primary efficacy end point of the trial. Two of the pre-specified secondary endpoints, tender joint count and morning stiffness, did show statistically significant improvement when compared to placebo. Based on the aggregate findings of the study, however, AtheroGenics is discontinuing clinical development of AGIX-4207 in rheumatoid arthritis.
Although we are disappointed with the results of the OSCAR study, we believe these results are compound-specific and that our v-protectant(TM) technology still offers great promise of yielding novel therapeutics to treat rheumatoid arthritis," commented Rob Scott, M.D., Senior Vice President of Clinical Development and Regulatory Affairs and Chief Medical Officer at AtheroGenics. "AtheroGenics continues to have an active program aimed at investigating second generation v-protectants(TM) in rheumatoid arthritis. We have identified other compounds with enhanced therapeutic potential within our industry-standard rheumatoid arthritis preclinical models and will be aggressively working to select another candidate to move into formal preclinical development."
The Phase II double-blinded, placebo-controlled, 12-week study involved 275 patients in multiple European centers with mild-to-severe rheumatoid arthritis. Study subjects were randomized into four groups receiving either placebo or one of three single daily oral doses of AGIX-4207: 75 mg, 150 mg or 225 mg. Study subjects who were previously treated with biological Disease Modifying Anti-Rheumatic Drugs (DMARDs) were not enrolled in the study nor were subjects who were taking non-biological DMARDs at the commencement of the study. Study subjects on Non-Steroidal Anti-Inflammatory Drugs (NSAIDS) including aspirin, COX-2 inhibitors and analgesics were allowed to remain on their drug regimens.
The primary endpoint of the study was improvement in ACR 20 scores, as measured after 12 weeks of treatment with AGIX-4207. An ACR 20 response is a preset standard from the American College of Rheumatology, which requires a greater than 20 percent reduction in swollen joint count, in tender joint count and in three out of five of the following: patient's assessment of pain, patient's assessment of disease activity, investigator's assessment of disease activity, acute phase reactant (ESR or CRP) and patient's assessment of functional status. In the analysis of all randomized patients, 25 percent of placebo-treated patients achieved an ACR 20 response at Week 12 compared with 20 percent at 75 mg, 15 percent at 150 mg, and 23 percent at 225 mg of AGIX- 4207-treated patients. The drug was generally well tolerated, and serious adverse events were similar to placebo. <<
By Adam Feuerstein Senior Writer 11/22/2004 2:33 PM EST
AtheroGenics (AGIX:Nasdaq) 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 Pfizer's (PFE:NYSE) 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[a lot 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. <<
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