The End Of Obesity As We Know It
Sanofi-Aventis' Acomplia promises that and more.
But approval isn't a slam dunk
December 17, 2004
By Kerry Capell and Carol Matlack
Ever wonder why marijuana smokers get the munchies?
So did a team of scientists at Sanofi Recherche lab
in Montpelier, France. Fifteen years ago they began
investigating marijuana's effects on the brain, including
the well-known fact that cannabis makes users hungry.
"We set out to try and create an anti-marijuana,"
a drug that could suppress appetite by blocking the
same switch in the brain activated by cannabis, says
Gérard Le Fur, senior executive vice-president
and board member at newly merged French pharmaceutical
giant Sanofi-Aventis (SNY ).
They succeeded beyond their wildest dreams, discovering
a medicine that not only helps people lose
weight but also shrinks abdominal fat, helps people
stop smoking, improves cholesterol levels, and helps
patients better regulate blood sugar.
Talk about a potential blockbuster. Initially, though,
Sanofi will take it slow. It will seek approval of the
drug, Acomplia, in Europe and the U.S. by the second
quarter of 2005 as a treatment for just two of the conditions:
obesity and tobacco addiction. Because patients in Acomplia
trials regained weight after stopping treatment, the
company hopes regulators will approve it for long-term
use.
Researchers say side effects such as nausea and depression
are relatively minor and short-lived. But as the first
in an entirely new class of drugs that affect a pleasure
center in the brain, even the slightest hint of psychiatric
side effects may lead regulators to demand more long-term
safety data, potentially delaying Acomplia's launch
beyond 2006 as planned. Still, Sanofi-Aventis is confident
that the drug's impressive efficacy will assuage any
such worries. "It's a product that takes aim at
two of the great maladies of the century," says
Sanofi-Aventis CEO Jean-François Dehecq.
DEPRESSION QUESTION
Acomplia is the first in a new class of compounds under
development to block receptors found in the brain and
in fat tissue known as cannabinoid type 1 (CB1). These
receptors control hunger and tobacco addiction. Chronic
overeating and smoking sends them into overdrive. Blocking
the CB1 receptors dramatically reduces such cravings.
Results of a two-year clinical trial in the U.S. showed
patients given Acomplia lost an average of 19 pounds,
compared with five pounds for patients given a placebo.
Those on Acomplia also reported higher levels of HDL,
the good cholesterol, lower levels of triglycerides,
and improved sensitivity to insulin. All are important
in keeping heart disease at bay. "This could be
a paradigm-shifting drug," says Dr. Louis J. Aronne,
president of the North American Society for the Study
of Obesity.
The market potential is huge. More than a third of
Americans are clinically obese, or 30% above their ideal
body weight. And it's not just an American phenomenon.
Dr. Gbola Amusa, senior research analyst for Sanford
C. Bernstein & Co. in London, estimates that as
much as 10% of health-care costs in other industrialized
countries are related to being overweight. The two leading
obesity drugs, Xenical and Meridia, have unpleasant
side effects such as diarrhea or high blood pressure,
so analysts think Acomplia will quickly win market share
if approved. Amusa estimates sales will reach $5.6 billion
a year by the end of the decade.
Accomplia's real potential may go well beyond eating
and smoking. The company hopes it will also become the
first drug approved for the treatment of metabolic syndrome,
a combination of abdominal fat, high blood pressure,
high blood-fat levels, low levels of HDL cholesterol,
and high blood-sugar levels, all of which contribute
to cardiovascular disease. "This is not just a
diet drug but a significant advancement in cardiovascular
treatment," says Amusa.
Still, there is reason for caution. There was a noticeable
rate of withdrawal in Acomplia's clinical trials due
to depression. Researchers involved in the trials say
that might be because people taking the drug went in
with unrealistic weight-loss expectations or were more
susceptible to depression to begin with.
Either way, there are no long-term studies yet of the
effects of interfering with this part of the brain.
And given the increased regulatory scrutiny on new drugs
after the Vioxx and antidepressant controversies, the
company may find it needs to submit more data than anticipated
to secure approval. Is Acomplia too good to be true?
"There has never been a diet drug approved that
has had more benefits than risks," says Dr. Larry
D. Sasich of Public Citizen's health research group
in Washington. Dehecq and Le Fur are determined to prove
doubters like him wrong.
Source:www.businessweek.com
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