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Roxanna Guilford-Blake
originally printed in BIO News -- Oct/Nov 2003
You've heard the words. Epidemic. Pandemic. A public health
crisis.
According to the Centers for Disease Control and Prevention
(CDC), 61 percent of Americans are considered overweight or obese, and that
number appears to be growing. In the past 15 years, the prevalence of obesity
among adults has increased by over 30 percent. Even more startling, over the
past two decades, it has increased 100 percent in children and adolescents.
Obesity-related deaths are on the rise as well, says the
CDC.
So the problem is significant, it's growing, it's
life-threatening—and it translates into a tremendous potential market.
In 2002, the market for anti-obesity drugs reached $520
million in the United States,
Europe and Japan.
More than half of the market—$350 million—was in the United
States, according to Carole D. Gleeson, an
analyst with Decision Resources, Inc.
K. V. Anantharaman, a Frost & Sullivan analyst, places
the current U.S.
market for anti-obesity drugs at approximately $300 million and ready to grow
dramatically. "The current burgeoning estimates of global obese population is
about 400 million, and the success of the drugs under development could
translate into a global multi-billion dollar market for anti-obesity
treatment," he says.
Steve Burrill, chief executive of Burrill & Company, a
San Francisco based life-sciences merchant bank, points out that the potential
market isn't limited to those with serious weight problems; it includes people
who want to lose just a few pounds and become trimmer. "You extend beyond just
the [truly] obese to a lifestyle and wellness [consumer]."
"According to experts we interviewed, the main reason why
current drugs are inadequate is that they do not help to sustain long-term
weight loss in most patients," says Gleeson. "Additionally, they point out that
only a minority of their patients lose 5 to 10
percent of their initial weight."
Meeting the Challenges
Given this market, it's no surprise that R&D activity is
going strong; Gleeson reports that more than 200 agents are in development,
most in the very early stages.
The company that develops a safe and truly effective
anti-obesity drug will receive a tremendous payoff. So why is it so difficult
to bring an anti-obesity drug to market? There are several reasons.
Complexity.
The etiology of obesity is not well understood. "So far, research shows that
the pathophysiology of feeding behavior is very complex and that the etiology
of obesity is multifactorial," Gleeson explains. "Therefore, developing a safe
and effective target is very difficult."
There's
no single solution, no single target, for solving obesity, agrees Burrill.
"It isn't like there is a single fat
gene . . . we can turn on and off."
Of
course, the multiplicity of targets also broadens the market, opening the door
for a variety of therapies from several companies. Safety and side effects. Even if a company can create an
effective antiobesity compound, there's a significant risk of an unacceptable
side-effect profile.
"It
is very difficult to disassociate the induction of weight loss from potentially
adverse effects on other metabolic processes, and for the most part,
anti-weight-gain drugs have had a net negative effect on personal health,"
explains Steven M. Watkins, Ph.D., president and chief scientific officer of
Lipomics Technologies, a West Sacramento, Calif.,
biotech company engaged in lipid research.
According
to Gleeson's research, this is a particular problem for companies developing
therapies with multiple targets. "Many experts we interviewed stated that a
drug that targets multiple pathways may likely be successful in terms of
efficacy; unfortunately, it may also have intolerable side effects."
And
of course, from a business perspective, "intolerable side effects" means
liability. Think fen-phen. (Fenfluramine, half of the duo, was pulled in 1997.)
But
while strong concerns about liability remain, the direct impact of fen-phen
depends upon which population you ask. According to Anantharaman, it has had a
negative effect on some doctors, making them warier of the potential side
effects of other such therapies.
But
the fen-phen downfall hasn't inhibited investors. "Fen-phens of the world come
and go," Burrill says. "It doesn't cause people like us not to make
investments."
Gleeson
agrees. "The problems with fen-phen did not stop drug development—particularly
of agents with different mechanisms of action."
All
it will take to banish the specter of fen-phen is a solid antiobesity
therapeutic to emerge on the market, says Anantharaman. Concern over fen-phen
makes the market "all the more receptive" to a safe and effective alternative.
"If companies can come out with the right products with minimal side effects,
then the confidence would come back."
And
that seems to be exactly what is taking place. Drugmakers are developing
antiobesity drugs that involve novel mechanisms of action and have limited side
effects compared with the existing anti-obesity drugs, he reports. Reimbursement. The reimbursement for antiobesity is only
about 35 percent of the total sales, reports Anantharaman. Since the rest
involve patients who pay out of pocket, the market is restricted to those who
are willing and able to do so.
And
many will eventually stop paying, warns Gleeson. "Most patients will
discontinue their therapy after several months because of the burden of
out-of-pocket expenses; according to doctors, many of their patients feel the
amount of weight loss they achieve is not worth the expense."
Burrill,
however, doesn't see this as a significant hurdle, predicting consumers will be
willing to pay for a safe, fast-acting, effective obesity therapy regardless of
reimbursement status. "The public's willingness to spend—whether or not it's
reimbursed by their health plan—on quickie solutions also adds to the enormous
opportunity." Keeping it off. Appetite may be difficult to suppress at
any point, but after initial weight loss, it becomes even more difficult. "It
has been proved that once the body loses about 10 to 15 percent of its weight,
there would be a strong urge to go on an eating overdrive to make up for the
lost weight," Anantharaman explains. "The patient's resistance to over-eating
is a challenge for the success of the anti-obesity treatment."
Watkins
agrees. "It's the long-term bounce back that has so far been unstoppable. Drugs
that prevent the regaining of weight—weight maintenance drugs—seem to possess
the highest potential for a successful intervention, but there aren't any
current examples of these types of drugs on the market."
Peering Down The Pipeline
Advancements in genomics and other areas have had a
tremendous impact on generating drug targets. For instance, mutations in
melanocortin receptors are the most common mutations found in severe,
early-onset obesity, reports Gleeson. Several agents targeting this system are
in early-stage development.
"But we need to keep in mind that as genomics research
identifies these genes that may be associated with obesity, researchers still
need to uncover the role of the proteins that are generated from those genes,"
she says.
Nevertheless, many insiders and observers expect to see the
marketplace transformed in the next three to 10 years. And the multiplicity of
targets means a multiplicity of solutions.
"The causes of obesity are likely to be quite varied; single
targets for modulating the disease are unlikely," says Watkins. "The most
likely scenario for a safe and efficacious weight-loss drug in the near future
is a drug that works for a specific and limited population. Because there are
multiple causes of obesity, the treatments are also likely to be selective and
personalized."
Burrill predicts an "explosion of products" over the next
three to five years—products that will have "real impact over the five- to
10-year period." He anticipates a broad array of products targeting different
receptors and different metabolites. (It won't all be therapies, he points out;
much will be done in the food and nutrition area.)
Anantharaman offers a similar timetable. "The market
expectations for new categories of drugs to be launched for antiobesity would
be the 2006–2008 time frame." He points out that five companies—Sanofi
Synthelabo, Regeneron, Takeda, Alizyme and Phytopharm—have products in the
advanced stages of clinical trials.
Roxanna Guilford-Blake is an Atlanta-based freelance writer.
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