By Ron Winslow
WASHINGTON--An experimental class of cholesterol-lowering drugs
is emerging as the most promising new weapon against cardiovascular
disease since the widely used medicines called statins first
reached the market more than 25 years ago, medical studies
show.
In a flurry of studies presented over the weekend at the annual
meeting of the American College of Cardiology, the drugs, known as
PCSK9 inhibitors, were shown to reduce LDL cholesterol levels by
half to two-thirds across several different patient groups.
Elevated LDL or bad cholesterol is a key risk factor for heart
attack and stroke.
The new reports included five late-stage or phase 3 studies
sponsored by Amgen Inc. (AMGN), another phase 3 trial from Sanofi
SA (SNY) and its partner Regeneron Pharmaceuticals Inc. (REGN), and
mid-stage or phase 2 data from Pfizer Inc. (PFE)
The companies are vying in a market that includes millions of
patients who can't control their cholesterol with statins, which
are among the most widely used and most lucrative drugs ever
developed by the pharmaceutical industry.
The new results are consistent with findings from earlier,
smaller studies of PCSK9 inhibitors, but suggest the drugs have a
durable effect on LDL cholesterol. No significant safety issues
turned up in patients followed for as long as year.
"There's not a shred of doubt that this is a very efficacious
way to lower LDL" cholesterol, said Steven Nissen, chairman of
cardiovascular medicine at the Cleveland Clinic, who wasn't
involved in any of the reported studies.
But he and other heart experts said important questions remain.
Chief among them is whether the dramatic reductions in LDL will
translate into meaningful reductions in heart attacks, strokes and
other serious consequences of cardiovascular disease.
"The preliminary data are very persuasive," said Sidney Smith, a
cardiologist at University of North Carolina, Chapel Hill. "But we
have to see the clinical outcomes."
All three companies have launched major studies to answer the
question but results generally aren't expected until 2018.
Meantime, companies expect that the U.S. Food and Drug
Administration will consider whether to approve the drugs based on
LDL lowering and other factors before the data on heart attacks and
other outcomes are in.
Statin therapy, exemplified by Pfizer's blockbuster Lipitor, has
been a mainstay strategy after diet and exercise for reducing heart
risk. Lipitor and most other statins have lost patent protection
and are now available in the U.S. for pennies a pill.
Under recently revised cholesterol guidelines, more than 50
million Americans are candidates for statin therapy, according to a
recent analysis by Duke University researchers in the New England
Journal of Medicine.
But estimates are that about 10% of people, or more than five
million, suffer muscle pain or other side effects that prevent them
from taking statins, or taking them at doses required to achieve
cholesterol-lowering goals.
Others can't reach their targets on aggressive regimens,
including people with genetically high levels of LDL. Merck &
Co.'s (MRK) ezetimibe modestly lowers LDL, but whether the way it
acts on cholesterol also reduces heart risk hasn't been proven.
The anti-PSCK9 agents include Amgen's evolocumab, alirocumab
from Sanofi and Regeneron and Pfizer's bococizumab. They are
bioengineered antibodies that block PCSK9, a protein that
interferes with LDL clearance--a different mechanism from how
statins work.
They are injected, much like insulin shots, and the companies
are studying biweekly and monthly regimens.
One of the new studies of Amgen's drug called Descartes
illustrates the effect of the agents. In the 901-patient study,
those treated with a 420 milligram dose once a month had a 57%
reduction in LDL compared with those who took a placebo.
The results were similar whether the drug was added to a
strategy of diet alone or three different intensities of statin
therapy, including one where ezetimibe was added to the highest
dose of generic Lipitor. Adverse events included upper respiratory
infection, flu and back pain. The study was also published online
by the New England Journal of Medicine.
Other Amgen studies showed significant LDL lowering in patients
with genetically high LDL and among those considered
statin-intolerant. The Sanofi-Regeneron trial, the first of about
10 phase 3 studies the companies expect to report out this year,
showed its drug was superior to ezetimibe in lowering LDL over six
months.
Write to Ron Winslow at Ron.Winslow@wsj.com
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