April 20, 2004 Checkup:Atherosclerosis Overview The
condition: Atherosclerosis, a disease affecting about 13
million Americans, causes plaque to accumulate on and in
artery walls, leading to heart attacks or strokes. What's
interesting about the condition: The buildup of plaque --
fatty deposits and other materials -- causes artery walls
to thicken, harden and create lesions that may rupture to
create blood clots. Atherosclerosis can go undetected for
years, and its cause is not known. Recent data have shown
inflammatory cells that try to repair cholesterol-laden
blood vessels play a large role in arterial swelling,
leading to atherosclerosis. For severe blockage, bypass
surgery, angioplasty or stenting is performed. Patients
must also change their diet, adopt an exercise regime and
take drugs to reduce fats and cholesterol. What's in the
pipeline: Newer drugs target inflammatory cells while
others boost high-density lipoproteins, also known as HDLs
or "good" cholesterol. Although HDLs may improve heart
health, no evidence has shown it can reduce heart attacks
occurrence or improve survival. AGI-1067/Atherogenics
(Phase III) Medical Benefit: AGI-1067, taken orally, blocks
a set of genes that cause inflammation. An antioxidant, AGI-
1067 may prevent low-density lipoproteins, also known as
LDLs or "bad" cholesterol, from oxidizing, a process
similar to rusting. By thwarting oxidation, the drug also
halts the production of molecules that can lead to
inflammation. AGI-1067 has shown no side effects, according
to Russell Medford, president and CEO of Atherogenics.
Company Benefit: Atherogenics is spending about $40 million
to fund its 4,000-patient Phase III trial. While Dr.
Medford did not say how much has been spent to develop AGI-
1067, the "vast bulk" of the total $65 million spent by
Atherogenics in fourth-quarter 2003 was for AGI-1067, he
said. Timing: Atherogenics began its Phase III trial in
February 2004 and expects to complete enrollment by the
middle of the year. The company aims to file an application
for Food and Drug Administration approval by end-2005, Dr.
Medford said. Antrin/Pharmacyclics (Phase II) Medical
Benefit: Antrin, delivered intravenously, targets plaque
that ruptures easily and comprises lipids and inflammatory
cells. Antrin, activated by red light via optical fiber,
can hone in on areas of plaque buildup and eliminate the
cells that can trigger inflammation. Side effects have been
minimal, with some numbness or tingling in the fingertips.
Company Benefit: Pharmacyclics has spent an estimated $50
million to develop Antrin, according to Richard Miller,
president and CEO. Dr. Miller said Pharmacyclics seeks to
work with a cardiovascular-disease company to further
develop Antrin. Timing: Pharmacyclics completed a Phase I
trial last September, and is planning its Phase II trial.
Antrin could reach the market in five years,
Dr. Miller said. Torcetrapib/Pfizer (Phase III) Medical
Benefit: Torcetrapib is taken orally and boosts HDLs by
prohibiting a protein from transferring cholesterol to
LDLs. In a recent trial, patients showed a 46% increase
in HDLs, while those who took torcetrapib coupled with
Pfizer's blockbuster statin, Lipitor, had a 61%
increase. In early testing, high doses of torcetrapib
raised blood pressure in some patients, a spokeswoman
said, prompting Pfizer to alter its dosing regiment in
subsequent trials. Company Benefit: Pfizer is spending
$800 million to develop torcetrapib. Once available, the
drug will be offered only in combination with Pfizer's
blockbuster statin, Lipitor, which lowers LDLs. A
torcetrapib/Lipitor combination drug is expected to reap
world-wide sales of $355 million in 2007 and $1.6
billion in 2008, according to Prudential Equity Group.
Timing: Pfizer began its Phase III trial at the end of
2003, but did not say when the final testing would be
complete. Tim Anderson, an analyst at Prudential Equity,
said there's "a low likelihood" torcetrapib would hit
the market before 2007.
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Winning against heart attack and stroke
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