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Drug Makers Refill Parched Pipelines
11 กรกฎาคม 2554
Date: 11 July 2011
Source: THE WALL STREET JOURNAL
The pharmaceutical industry, after years of research flops that led some to
write its obituary, shows signs it is coming back to life.
Credit a revamped research approach by the industry, which, after years of
focusing on me-too drugs for ills that were already well treated, is pouring
firepower into diseases that aren`t.
Companies have won marketing approval so far this year for 20 innovative
medicines that work differently or better than existing drugs, or tackle
ailments lacking good treatments, according to the Food and Drug
Administration. "New molecular entities," the FDA calls them. There
were just 21 such approvals all last year.
Recently approved are the first therapy shown to extend life for people with
advanced melanoma, the deadly skin cancer; the first new treatment for lupus in
over 50 years; and two drugs for hepatitis C that are far more effective than
current care.
"We`re seeing a lot of innovation, much more than in recent memory,"
said Janet Woodcock, director of the FDA`s drug division, calling today`s
laboratory output a "turning point" in drug development.
She added: "If you`re a patient with a terrible disease, a serious cancer
or something like that, I think you ought to take heart from what we are
seeing."
That would include Sharon Belvin, who was diagnosed at age 22 with melanoma
that had spread, but who, in a 2005 clinical trial, received the melanoma drug
that has just been approved. Ms. Belvin is now a 29-year-old mother of two with
no sign of the disease.
"It is not just the risky, nimble biotechs that
are developing these novel agents," said Ms. Belvin`s doctor, Jedd Wolchok
of Memorial Sloan-Kettering Cancer Center in New York. "It is the large
pharma companies that are making substantial commitments to a field that was
considered very speculative until recently."
Results can`t come soon enough for these companies. They are losing patent
protection on a host of big sellers, including the biggest of all, Pfizer Inc.`s
cholesterol drug Lipitor, which goes off-patent in November. Companies are
looking at a cumulative loss of more than $100 billion in revenue through 2015,
by some estimates, as these drugs face competition from low-priced generics.
The new medicines can`t avert a tumble from this steep "patent cliff"
but should cushion it. While they don`t promise annual sales anywhere near
Lipitor`s $11 billion, they belie a common supposition that the drug-industry
pipeline is skimpy. More than 20 innovative drugs with the potential for annual
sales of $1 billion or more each have strong odds of winning FDA approval over
the next three years, according to a Credit Suisse analyst, Catherine Arnold.
Some could stumble. In January, Merck & Co. scaled back studies of a highly
anticipated heart drug after some patients it was being tested on suffered
strokes. Merck says it is still pursuing the drug.
In addition, new drugs today arrive in a more cost-conscious marketplace. With
generic drugs available for a growing list of conditions, from high blood
pressure to high cholesterol, U.S. health plans and foreign governments` health
systems are demanding evidence that new medicines are better before agreeing to
pay for them.
That is one reason for drug companies` increased focus on innovation. Gone are
the days when they could make a few changes in a stomach-acid or depression
drug that was facing patent expiration -- tweaking it enough to get a new
patent -- and reap many more years of brand-name-drug sales.
But if they can offer the only effective treatment for a serious disease, it is
all but certain health plans will cover the drug, even if the company sets a
skyhigh price.
Because developing drugs takes many years, changes in how companies approach
the process take a long time to show effects. Today`s new-drug output appears
to mark the beginnings of a payoff from a research reorientation the industry
began undertaking several years ago, after a string of flops.
The low point came in 2006 with the failure of a heart drug Pfizer saw as a
successor to Lipitor. A compound called torcetrapib raised so-called good
cholesterol, and Pfizer championed it -- right up to the moment that a board
monitoring the testing learned it was increasing patients` risk of dying.
Sixteen years of research and nearly $800 million went down the drain.
By then, observers both inside and outside the industry were finding fault with
what was sometimes described as companies` industrialized approach to drug
discovery. They had built huge laboratories covering all aspects of drug
development. Management tightly controlled research programs, reviewing
projects for their commercial potential and requiring researchers to provide
regular updates.
Scientists also had to keep their work secret, exploring new medicines without
insight from outsiders. But companies can`t keep a tight leash on their
researchers if they expect to capitalize on the deepening understanding of how
diseases happen, contends the chief executive of Sanofi SA, Christopher
Viehbacher.
Cost was also an issue. Prescription-drug companies spent $45.8 billion on
research and development, or 17% of their revenue, in 2006, according to
Bernstein Research. "The mass-production approach is not going to help you
to be productive in a financially sound manner," says Mikael Dolsten, who
heads Pfizer`s research and development. Some investors and consultants began
to question why the industry was investing in drug research at all, rather than
just identifying promising work by small firms hatched from university labs,
and then teaming up with them.
The new melanoma drug emerged from a more
collaborative approach.
Bristol-Myers Squibb Co. capped its research budget
a few years ago to "create a culture" that encouraged collaboration
with outsiders, says R&D chief Elliott Sigal, both to save money and to
capture new scientific approaches.
Among these approaches was enlisting the body`s immune system to fight cancer,
instead of just assaulting it with toxic medicines as in chemotherapy.
Hopes of spurring immune-system attacks on cancer had frustrated researchers.
But in the 1990s, a scientist then at the University of California, Berkeley,
made a discovery: A certain molecule was serving as a kind of traffic cop,
telling the immune system`s attack cells when they should launch an assault and
when they should hold off.
The scientist, James Allison, couldn`t interest big pharmaceutical companies in
exploring this. At that time, they saw themselves as competing against academic
scientists.
Only small biotechs were interested. Eventually, Dr. Allison joined with one
called Medarex Inc. in Princeton, N.J., to see if they could release the
molecular brakes on the immune system and let it attack a tumor.
Their work caught the attention of Bristol-Myers. In 2004, Bristol-Myers formed
a partnership with Medarex. The big company agreed to pay the little one $50
million up front and as much as $205 million if certain regulatory goals were
met.
Expensive as that sounds, it was a relative bargain in the world of drug
development, where a pharmaceutical company can spend up to $1 billion
developing a drug in-house from start to finish.
And not having the Medarex labs and researchers on its books meant
Bristol-Myers could walk away if the approach didn`t appear to be working.
But it did. When Ms. Belvin`s melanoma was first diagnosed in mid-2004, tumors
that had spread to the young woman`s lungs "lit up like a Christmas
tree" on a CT scan, she recalls today. Dr. Wolchok prescribed several
months of chemo, to limited effect. Then two courses of another existing drug,
interleukin-2, made the tumors in her lungs worse, and made her skin peel off.
"It was hell on earth," she says.
In September 2005, Dr. Wolchok enrolled Ms. Belvin in a trial started by
Bristol-Myers and its biotech partner to test the immune-system approach to
fighting cancer. Though she might have gotten a placebo, it turned out she did
receive the chemical compound the companies were testing, called ipilimumab.
Within four months, scans showed her tumors melting away. After several more
months, there was no sign of them.
"It`s because the doctors and the people who worked on it had the
foresight to think out of the box," Ms. Belvin says.
The benefit to many others in the trial was far less, just a median four-month
increase in survival. This March, that proved enough to win FDA approval of the
drug for Bristol-Myers, which by that time had purchased full control of
Medarex, for $2.1 billion.
Bristol-Myers now counts on such collaborations to gain access to "a
bigger universe of innovation, and also balance the tremendous failure rates
you see in the industry," says its Dr. Sigal. The pharmaceutical industry
as a whole has spent more than $130 billion acquiring small biotechs since
2006.
Bristol-Myers named the melanoma drug Yervoy and plans to charge $120,000 for a
course of treatment. Steep as that is, insurers are expected to cover the drug,
given the lack of alternatives. Analysts predict annual sales will eventually
top $1.2 billion.
It could soon get some company. Already under review at the FDA is another
melanoma drug -- based on yet another new therapeutic approach. This one comes
from units of Roche Holding AG and Japan`s Daiichi Sankyo Co.
Says Pfizer`s Mr. Dolsten: "We`re coming back to a period where companies
are starting to grow and have a reasonable flow in their pipelines again."
Keywords: Pharmaceutical / FDA / US / Drugs /
Health