§
AGI-1067 lowers both
fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) (statistically
significant).
§
AGI-1067 caused a 0.5
percent decrease in HbA1c at 12 months (p<0.0001) despite all of the
patients being well-controlled with a mean baseline HbA1c of 7.2 percent.
Note: HbA1c Goals:
§
Patients
taking AGI-1067 were 63
percent less likely to develop new onset diabetes (p<0.0001).
AGI-1067 for Atherosclerosis
Our lead product candidate, AGI-1067, is a novel small molecule with anti-oxidant and anti-inflammatory properties that was discovered by
AtheroGenics and designed to treat atherosclerosis of the blood vessels of the heart, or coronary artery disease. AGI-1067 works by
inhibiting key oxidant signals within cells of blood vessel walls that generate inflammatory processes that are key to the pathogenesis
of atherosclerosis. This includes inhibition of inflammatory cytokines, chemokines and vascular adhesion molecules that participate in
the initiation, growth and eventual destabilization of the plaque. Its anti-oxidant properties also play a role in its ability to
inhibit the formation of oxidized LDL, a critical component in the formation of atherosclerotic plaque.
AGI-1067 was studied pre-clinically in multiple species to establish its
therapeutic properties. Dosed orally, AGI-1067 blocked VCAM-1 expression,
prevented
atherosclerosis and showed potent
anti-oxidant activity. Based upon the successful completion of pre-clinical
testing, AGI-1067 was studied in seven Phase I clinical trials in more than
150 men and women, including healthy volunteers and patients up to the age
of 85, to assess tolerability and potential for interaction with other
drugs. In addition, we have given AGI-1067 in combination with other drugs
commonly used in patients with
atherosclerosis.
In these clinical trials the subjects tolerated AGI-1067 well, with no dose
or use-limiting side effects. These positive results supported our progress
to Phase II clinical trials.
A Phase II proof-of-concept dose-finding clinical study (Canadian Antioxidant Restenosis Trial (CART-1)) using an
intravascular ultrasound (IVUS) for directly visualizing coronary artery vessel walls concluded that AGI-1067 was
effective both at reducing the rate of restenosis in patients undergoing an elective PTCA as well as reversing native
atherosclerosis in a non-intervened segment of coronary artery. The study also demonstrated an effect on coronary inflammation
in that the IVUS measurements of plaque volume were mirrored by reductions in fibrinogen, a cardiac risk marker that doctors use
to help determine a patient's overall risk of developing cardiovascular disease. This was despite a relatively short treatment
duration of six weeks with follow up at six months. AGI-1067 was well tolerated and there were no safety concerns.
Based on the results of an End of Phase II meeting with the U.S. Food and
Drug Administration in 2002 and a subsequent FDA Special Protocol
Assessment in early 2003, AtheroGenics has initiated a pivotal Phase III
clinical trial to further evaluate the benefit of AGI-1067 for the treatment of
atherosclerosis.
AGI-1067 was studied in a 12-month Phase IIb clinical trial (CART-2) that assessed the effect of once-daily oral doses
of AGI-1067 on atherosclerosis. The primary endpoint of the trial was a change in coronary atherosclerosis, measured as
total plaque volume after a 12-month treatment period, compared to baseline values. Combined results of the final analysis
indicated that AGI-1067 reduced plaque volume by an average of 2.3%, which was statistically significant (p=0.0015). An
important secondary endpoint from the trial, change in plaque volume in the most severely diseased sub segment, also shows
significant regression (p=0.0001) from baseline by an average of 4.8%. Overall adverse event rates were similar in the AGI-1067
and “standard of care” (placebo) groups, and AGI-1067 was generally well tolerated.
ARISE PHASE III CLINICAL STUDY
ARISE (Aggressive Reduction of Inflammation Stops Events) was a Phase III, double-blind,
placebo-controlled outcomes study designed to evaluate AGI-1067 in patients with recent acute
coronary syndrome (ACS). The study enrolled 6,144 patients and was conducted in 261 cardiac centers
in the United States, United Kingdom, Canada and South Africa. The primary endpoint in the ARISE study
was to compare the effect of 300 mg of AGI-1067 to placebo on the time to first incidence of a composite
of major adverse cardiovascular events (MACE), specifically cardiovascular death, resuscitated cardiac arrest,
myocardial infarction, stroke, need for coronary revascularization and admission to hospital for unstable angina.
The dosing period averaged approximately 24 months. All patients in the study were well-treated with the appropriate
standard of care. Standard-of-care therapies included lipid lowering, blood pressure, anti-platelet and other medications.
AtheroGenics recently completed the ARISE Phase III clinical study. Results of the ARISE trial were presented at the American
College of Cardiology Annual Scientific Sessions in March 2007. For a copy of the press release and study results,
please
click here.
AGI-1096 for Transplant Rejection
AGI-1096 is a novel oral antioxidant and selective anti-inflammatory agent that is
being developed to address the accelerated inflammation of grafted blood vessels,
known as transplant arteritis, common in chronic organ transplant rejection. AGI-1096
has completed a Phase I clinical trial investigating its safety and tolerability in
combination with tacrolimus (Prograf ®) in healthy volunteers. The results of the
Phase I study found that regimens of AGI-1096 administered alone, and concomitant with tacrolimus,
were generally well-tolerated at all oral doses, and there were no serious adverse events
associated with either regimen during the study.
