Cholesterol drugs:

Cholesterol is controlled by a hormone
in the brain. Increased levels of ghrelin
not only make the lab mice eat more
and gain weight, but also increases the
levels of 'bad' cholesterol in their blood.

Statins are the current standard for
cholesterol management and they are

Yet many patients have problems
achieving their cholesterol goals.
Moreover, some patients are unable to
tolerate statin therapy.

PCSK9 inhibitors are the next big idea.
Besides Amgen, several other
companies are working on developing
PCSK9 inhibitors.

The world's biggest drugmakers are
racing to market the first medicine to
tap into a gene mutation that drops
heart-attack risk by as much as 88

Normally, the PCSK9 gene creates a
protein that disrupts the ability of liver
cells to remove bad cholesterol from
blood, enabling it to accumulate. A
mutated form of the DNA found in 3
percent of people, lowers levels of the
protein, allowing more of the artery-
clogging hormones to be swept away.

Amgen's experimental AMG 145, a fully
human monoclonal antibody, is a
PCSK9 inhibitor.

In March 2012 Amgen presented
positive data on its
hypercholesterolemia candidate,
AMG145. Results were presented at
the American College of Cardiology
Scientific Session from a phase Ib
study that was conducted in high
cholesterol patients taking statins.

The phase Ib study was conducted to
evaluate the safety, efficacy and
tolerability of AMG145 compared to
placebo. Results showed that patients
on low to moderate doses of statin
experienced a mean reduction in LDL-
C (bad cholesterol) levels of up to 75%
at week 6 when administered AMG145
every two weeks.

In the 51-patient study, patients
receiving monthly injections of AMG
145 and taking low to moderate doses
of statins had up to a 66 percent
reduction in "bad" LDL cholesterol by
the eighth week of the study.

AMG145 is currently in a phase II
program consisting of six studies which
will involve about 1,900 patients. The
program will not only evaluate AMG145
plus statins in patients with or at risk
for cardiovascular disease, it will also
be studied in patients who cannot
tolerate statins.

Other companies pursuing research
on this front are Merck & Co., Isis
Pharmaceuticals Inc. with partner
Bristol-Myers Squibb Co. and Alnylam
Pharmaceuticals Inc.

In July 2011, Pfizer, the world's biggest
drugmaker, began a second-stage
testing of its anti-PCSK9 antibody,

But ahead of all of them is Regeneron.
Regeneron is developing its entry,
called REGN 727, in partnership with
French drugmaker Sanofi. The
product, which has completed mid-
stage trials and is heading toward far
larger Phase III studies, has been
considered to be the clear front runner.

Amgen's drug, AMG 145, is just
entering mid-stage studies and is
considered about a year behind REGN
727 in development.

Regeneron's second-stage trials
showed that adding their PCSK9 drug
to high doses of Lipitor lowered
cholesterol by 65 percent versus a 17
percent reduction for high-dose Lipitor

In January 2012 Alnylam
Pharmaceuticals  announced positive
preliminary results from its ongoing
clinical trial of ALN-PCS, an RNAi
therapeutic targeting PCSK9 for the
treatment of severe
hypercholesterolemia. ALN-PCS
demonstrated statistically significant
RNAi silencing of PCSK9 of up to 66%
and reductions of up to over 50% in
levels of low-density lipoprotein
cholesterol (LDL-C), or "bad"
cholesterol, a clinically validated

This Phase I study continues with
planned dose escalation. Additional
results of the study are expected in the
first half of 2012.

The National Institute of Health  has
stopped a study with Abbott
Laboratories' cholesterol fighter
Niaspan 18 months early after results
showed the drug failed to prevent
heart attacks and even may have
boosted stroke risk.

The AIM-HIGH trial enrolled 3,414
participants in the U.S. and Canada
with a history of cardiovascular
disease who were taking a statin drug
to keep their LDL cholesterol low.
Study participants also had low HDL
cholesterol and high triglycerides.
Eligible participants received either
Niaspan in gradually increasing doses
up to 2,000 mg per day or a placebo
treatment. All participants were
prescribed Zocor (simvastatin), and
515 participants were given a second
LDL cholesterol-lowering drug, Zetia
(ezetimibe) to maintain LDL cholesterol
levels at the target range between 40-
80 mg/dL.

Abbott paid $3.4 billion for Kos
Pharmaceuticals in 2006 to acquire
Niaspan, a version of niacin that has
led a new wave of heart drugs to raise
good cholesterol. The findings may
also jeopardize medicines in that group
being developed by Merck, Eli Lilly and

An experimental drug from Merck &
Co. raised levels of good cholesterol,
slashed bad cholesterol and may have
helped patients avert heart
complications, without the safety risks
that prompted Pfizer Inc. to abandon a
similar product four years ago.

Patients on the treatment, called
anacetrapib, had a 40 percent drop in
bad cholesterol and a 138 percent rise
in the good cholesterol that ferries fat
from the blood, the study found.
Sixteen people on the drug died, had
heart attacks or strokes, compared
with 21 on a placebo. The 1,623
patient trial was funded by  New Jersey-
based Merck.

Roche  and Eli Lilly  have similar drugs
in development.

Isis Pharmaceuticals and Genzyme
said its drug mipomersen significantly
lowered LDL, the so-called bad
cholesterol, in patients who still had
very high cholesterol levels despite
taking the highest tolerable dose of
The FDA has safety concerns
regarding this drug.

Mipomersen would be Isis’s first big
product and would validate its “anti-
sense” technology for turning off

In one trial, patients who took
mipomersen had an average reduction
of 36 percent in LDL after 26 weeks,
while those getting a placebo had a 13
percent increase. In the other study,
those who got the drug had a
reduction of 37 percent versus a
reduction of 5 percent for a placebo.

Yet more than 20 percent of the
patients in each of the trials dropped
out because of side effects. The
biggest concern is that the drug might
cause liver damage.


Potential blockbuster: Lomitapide by
Aegerion Pharmaceuticals (In Phase 3),

Cholesterol cleaning vaccine: CVX-
210H vaccine, produced by Cardiovax:
The treatment works by reversing  the
narrowing of the arteries, it activates
antibodies to remove the LDL, but also
activates 'regulatory' cells  which stop
the immune system becoming
aggressive and causing inflammation,
in trial;

Procedure: Apheresis (similar to
Kidney Dialysis) by Baxter or Fenwal;

Cholesterol lowering alternatives:
Research  indicates that for most
people, consuming two handfuls of
nuts a day appears to be useful.
The findings apply to tree nuts such as
walnuts, almonds, pistachios,
macadamias, hazelnuts and peanuts.