Thanks to Gina for sending us the following article...Myrl
Drug makers now confront unlikely foe in labs: science
Discovery of medicines slows despite billions in investments
Sunday, February 13, 2005
BY KITTA MacPHERSON AND ED SILVERMAN
Star-Ledger Staff
http://www.nj.com/news/ledger/index.ssf?/base/news-20/110827559541270.xml
For the past 10 years, Janet Woodcock, one of the Food and Drug
Administration's top officials, has maintained "The List," a catalog of
diseases that desperately need new treatments.
It's a sorry compendium of incurable illnesses. Advanced breast cancer.
Alzheimer's. Autism. Adolescent depression. Diabetes. Lupus. Multiple
sclerosis. Obesity. Schizophrenia.
Woodcock's hope is to cajole the drug industry into forging a golden
age of discovery, something supposed to have happened by now.
But the reality is that the pharmaceutical industry isn't about to
produce miracles any time soon. The word inside labs, cor****ate board
rooms and regulatory cubicles is hauntingly consistent: The science is
too difficult.
"The low-hanging fruit is all gone, and the unique op****tunities are
difficult to come by," said Irwin Lerner, a former chief executive at
Hoffmann-La Roche, a Swiss drug maker with U.S. headquarters in Nutley.
"There's been a real failure that, despite billions of dollars in
investment, research hasn't conquered the diseases that haunt us."
Or, as Woodcock, director of FDA's Center for Drug Evaluation and
Research, says, "Some of these things are going to be really hard."
Like an oil pipeline running dry, the number of im****tant new medicines
generated by pharmaceutical laboratories has slowed to a trickle at a
defining moment for the industry. New concerns about product safety,
pricing and government oversight have thrown companies under piercing
scrutiny and raised new questions about their lack of innovation.
Even scientists from leading drug firms admit their spark has been
snuffed.
According to a survey published last week by Kline & Co., a consulting
firm in Little Falls, scientists claim they are working harder and
completing more projects, but they also believe research and
development productivity has dropped.
"In an increasingly difficult market with exceptionally high
expectations, they admit they need help," said Steve Chen, industry
manager for Kline's health care division.
Finding a way to refuel the drug pipeline is imperative, experts say,
because:
The pharmaceutical industry is the world's medicine chest. If firms
stopped providing truly innovative treatments, many hoped-for medical
advances would never materialize. It is not an exaggeration to say
millions of lives hang in the balance.
The lack of new drugs hurts companies' abilities to grow, which could
lead to downsizing or more consolidation among the remaining drug
makers. Either would offer an ominous forecast for New Jersey, where
the industry employs about 65,000 people.
Industry critics suggest a lack of new products can tempt
pharmaceutical executives to be slow in pulling popular products from
the market when safety issues arise. Pharmaceutical officials strongly
deny this suggestion.
Without pharmaceutical innovations, health care costs will continue to
rise because more patients will require hospital stays rather than be
treated with medication.
Faced with this clogged pipeline and other pressures -- notably
investor demands for consistent profits -- the big drug companies are
changing the way they do business.
There has been a recent lust for mergers, where companies acquire
rivals mainly for one or two big-selling products. There is an emerging
pattern of companies turning their backs on new treatments deemed not
profitable enough. And companies are investing heavily in biotechs,
whose smaller, nimble operations yield some of the most promising
treatments.
These new moves, experts like Lerner say, may not be enough to generate
the new drugs demanded by patients and investors, and the stakes are
enormous. Already, half of all Americans take at least one prescription
drug and 50 percent of seniors rely on three or more, according to
industry statistics.
This paucity of invention is a hot topic in the pharmaceutical
industry, but mostly behind closed doors.
"It's the billion-dollar question that no one in the industry wants to
talk about," said Peter Rost, a Pfizer vice president of marketing.
"How many breakthrough drugs have there been in recent years?" asked
Barbara Brenner, a patient activist and executive director of Breast
Cancer Action in San Francisco. By "breakthrough," she means fulfilling
a genuine, unmet need, not a "copycat" drug.
"I can only think of three," she said. "Gleevec, Herceptin and the
aromatase inhibitors. That isn't much, considering the public
investment. All of the areas they are looking at now, including cancer,
are much more complicated than the problems investigated in the past."
Gleevec is a leukemia drug made by Novartis. Herceptin, a Genentech
product, treats some forms of breast cancer. Aromatase inhibitors are a
new type of breast-cancer treatment made by several firms.
MILLION-DOLLAR BABY
Breakthrough drugs are difficult, risky and expensive to discover.
The Tufts University Center for the Study of Drug Development, a
Boston-based think tank, estimates it costs about $800 million to bring
a drug to market, where it can be sold exclusively for up to 20 years,
sometimes more, until its patent expires. Combine that with the
scientific difficulties that must be conquered and it's little wonder,
experts say, that companies are more reluctant to take big risks.
"Working on treatments for chronic diseases has a better potential
economic payoff, but companies are looking for op****tunities to fulfill
unmet medical needs," said Alan Goldhammer, a spokesman for the
Pharmaceutical Research and Manufacturers of America in Wa****ngton,
D.C., the industry trade group.
Drug companies got a taste for the easy hit more than a decade ago with
medical advances into the workings of the cardiovascular system. This
resulted in drug makers scrambling to develop their own medications to
treat ailments, such as high blood pressure and cholesterol.
Beyond heart disease, there were new pills for allergies, chronic pain
and new "lifestyle" drugs -- a category that would continue to grow
with im****tance. The era of the blockbuster drug had dawned. Think
Lipitor or Zoloft or Norvasc.
Times were good. Profits were high. Investors were happy. The drug
companies heavily promoted medications to doctors and consumers.
The money flowed.
To peddle these new products, pharmaceutical companies needed large
sales teams and marketing budgets to consistently deliver the big
profits Wall Street expected.
The excitement was not limited to the marketing folks.
Researchers stepped up their hunt for new drugs. Pulling drug
candidates from their vast libraries of compounds, they used the "spray
and pray" technique, lacing petri dishes laden with disease agents with
slightly varying sequences of experimental compounds and watching what
happened.
In 1996, companies filed 45 applications to the FDA to review "new
molecular entities," one of the most ever for new drug compounds. The
figures remained high -- until recently. The number of applications
bottomed out at 23 in 2002 and remains low.
Also worrisome is that new drugs are failing safety tests at a higher
rate than in the past. In the 1980s, about 14 percent of all drugs
submitted for review were approved. Today the success rate has dropped
to about 8 percent. Approximately 50 percent of new drugs fail to
produce adequate evidence of safety and effectiveness in the late
stages of Phase 3 studies, and cannot be approved, according to the
FDA.
Like a savvy Broadway producer with a hit and eager investors waiting
in line, drug makers soon found it harder to churn out smash after
smash.
Ultimately, the companies found it's "very difficult to feed that large
giant," said Ray Zoeller, vice president of planning and business
development for Thomson Healthcare, a publi****ng company that closely
tracks the industry.
THE PICASSO PILL
Leads for new medicines began slowing just as pressure was building
pipelines to spit out the next round of big sellers.
Look at the problem this way: If a drug maker rings up $30 billion in
sales each year, the surest way to achieve at least the 10 percent
growth Wall Street expected is to come up with one blockbuster. Even a
drug that generates $150 million in annual sales won't move the meter
very much.
For that reason, drug makers became quicker to reject safe and
effective pills that had poor big-profit potential.
"Every blockbuster is a Picasso painting," said Rost. But, as the
Pfizer executive cautioned, "You can't produce a Picasso on a conveyor
belt."
By 2000, nervous industry executives were looking into a nearly empty
pipeline and decided to dedicate millions of dollars to finding more
innovative drugs.
They invested in robotic drug testing kits, but failed to improve their
success rate.
And companies, euphoric over the sequencing of the human genome, hired
"genomics" teams, hoping to usher in an era of personalized medicine.
Many have since scaled back those operations mainly because they don't
know how to adapt their mass-market methods to products targeting small
groups.
Some industry insiders say such research investment is nothing more
than an attempt to impress investors.
"There's a tendency for big companies to play by a scorecard," said
Tuan Ha-Ngoc, chief executive of GenPath Pharmaceuticals, a biotech
based in Cambridge, Mass. "Sometimes, they move things along too
quickly. I'm worried many have sacrificed quality for quantity."
And then there are times when companies kill off viable drugs late in
the game for economic reasons. It's an industrywide practice, said Ken
Kaitin at Tufts University.
For example, last September Bristol-Myers Squibb discontinued for
"commercial reasons" a closely watched diabetes treatment, according to
Thomson CenterWatch, which tracks clinical trials.
Earlier this month, Enzon Pharmaceuticals of Bridgewater halted work on
an anti-cancer compound after analyzing Phase 2 data and deciding the
financial risks weren't worth it, according to a spokesman.
Drugs for several types of cancers, and a variety of diseases,
including sickle cell and Crohn's disease, have been scrapped by
prominent companies for similar economic reasons. In effect, product
development is moving toward an all-or-nothing approach in many labs.
The numbers of drug candidates successfully making it through the
lengthy development process would seem to indicate just that. Last
year, companies submitted 28 drug candidates for FDA review, not much
higher than the all-time low industry hit in 2002.
Some critics say drug companies also wall themselves off from
alternative sources of innovation. Before Daniel Scola Jr., joined the
law firm of Hoffmann and Baron as a patent attorney, he worked at
Warner-Lambert, which developed the revolutionary cholesterol-lowering
drug Lipitor. His job at Warner-Lambert, he said, was to fend off
inquiries from the outside for fear they would cause problems with
patent applications for company products.
"They won't deal with individuals," he said of the big drug makers.
Individuals like Scola's client, Peter Mueller.
The Princeton neuropsychiatrist believes the drug Meridia can
successfully treat such ailments as post-traumatic stress disorder,
fibromyalgia and Tourettes.
He obtained a "use patent" for the pill made by Abbott Pharmaceuticals
but cannot persuade the company to scientifically investigate his
claims and distribute the drug for these purposes.
"With Meridia, our focus is on obesity," said Laureen Cassidy, an
Abbott spokeswoman.
At weekly Friday clinics in his office, Mueller offers free help to
mental patients, many from out of state, and often dispenses Meridia as
an off-label use for their ills. "Unfortunately, the drug companies are
afflicted with the NIH syndrome, which stands for 'not invented here',"
Mueller said. "It's a tragedy."
As a result, the biggest drug makers may come to resemble a Hollywood
studio that doesn't make many of its own films, but instead acquires
and distributes sure hits created by smaller players. It's the reason
Pfizer -- the largest drug company in the world -- bought
Warner-Lambert.
"Many companies are going to change," said Michael Ferrante, a director
in the pharmaceutical research and development practice at
PriceWaterhouseCoopers, the consulting firm. "Some are choosing to
become marketing machines. They'll divest all basic research and hold
onto only late-stage development and marketing."
In effect, they'll be closing their pipelines all together.
Or some, like Merck, which has always hinged its cor****ate image on its
research excellence, will find ways to improve the odds of picking the
right drugs. Right now the company is betting big on computer programs
that can predict if a person is a good candidate for a particular drug
or clinical trial.
"The entire industry has been caught up in a constrained definition of
innovation," said Roger Longman, editor of In Vivo, an industry trade
magazine. "They've spent a great deal of effort looking for new
molecules to treat new diseases, but ignored op****tunities for existing
molecules. The issue is where are they looking for innovation?"
Regardless of where companies look, analysts such as Patricia Reilly of
Life Science Insights, a consulting firm, are growing more convinced
that "the blockbuster era is coming to an end."
And when it does, Reilly said, "companies are going to have to find new
ways to innovate."
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