FWIW, there's no news on the IMS data in the electonic version of WSJ. Only news today is the following which indicates, as most everyone knows, that PFE clearly has other drugs to add to the bottom line.
Anyone know if IMS releases data for any of the other PFE drugs?
+++++
Drugs:
Drug Makers' Goal: Prozac Without
the Lag
----
By Thomas M. Burton
Staff Reporter of The Wall Street Journal
The drug industry is in a high-stakes race to produce a faster-acting remedy for depression.
Few products in recent medical history have had as big an impact as the leading antidepressant,
Prozac, and its top competitors, Zoloft and Paxil. Together the three drugs account for sales of
more than $5.5 billion a year and are improving the lives of millions of patients.
But there's a big catch: The medications typically take two to six weeks-or even longer-to really
work. That can be a lifetime for someone with severe depression, particularly now that
insurance restrictions make it more difficult than ever to hospitalize long-term mental-illness
patients.
As a result, finding a quicker cure "has been one of the Holy Grails of psychiatry," says
Andrew A. Nierenberg, associate director of the depression program at Massachusetts General
Hospital.
Leading the quest are Prozac's maker, Eli Lilly & Co.; Pfizer Inc., which makes Zoloft, and
SmithKline Beecham PLC, Paxil's supplier. Other major players include Bristol-Myers Squibb
Co., which makes another competing drug, Serzone; Glaxo-Wellcome PLC, makers of the
antidepressant Wellbutrin; Johnson & Johnson and Boehringer Ingelheim AG.
The most intensive research focuses on one curious aspect of the human brain's physiology: Its
tendency to resist the biochemical effects of most of the current top-selling drugs for the first
few weeks.
Prozac, Zoloft and Paxil all act by increasing the amount of the chemical serotonin in the brain.
Serotonin is a so-called neurotransmitter, a chemical messenger that helps brain cells, called
neurons, send information to each other. Higher levels of serotonin are crucial to better moods.
Tiny points called receptors on each brain cell are the brain-cell components that "talk" to each
other through the serotonin. But certain receptors, called the 1A and 1D receptors, become
desensitized to serotonin immediately after there is a sharp increase in the brain's serotonin
level.
This inhibits the antidepressants' mood-improving activity from getting started for several
weeks. "It's as if there's a foot on the accelerator and another one on the brake, so the net effect
is the car isn't moving too fast," says Lilly's Steven M. Paul, vice president of discovery
research.
Finding a drug to take the foot off the brake "is where the big action is now," says Perry
Molinoff, vice president of neuroscience drug discovery at Bristol-Myers. All the major
research players are focusing on this approach, among others.
Intense and animated, the 47-year-old Dr. Paul worked under Nobel laureate Julius Axelrod at
the National Institute of Mental Health. Scientists working under him have identified at least
three compounds that, in laboratory rats, quickly produce the higher serotonin levels or other
biochemical effects believed to relieve depression, though the company declines to specify how
they work. Dr. Paul says he expects human clinical studies on various companies' drugs to be
nearly complete within two to four years.
Bristol-Myers has also isolated chemicals that seem to be faster-acting and more effective.
Improving the efficacy is also important, because about 25% of depressed patients don't seem
to respond to any drug, and many others respond only partially.
Heading the Bristol-Myers effort is Arlene Eison, 44, the company's principal scientist in
neuroscience drug discovery. She originally became interested in mental-health drugs when she
was a high school student working with autistic children at Camarillo State Hospital in
California. At Bristol-Myers, her work on two serotonin-based drugs -- the antidepressant
Serzone and the anxiety drug Buspar -- led to the current research.
One approach at Bristol-Myers is to find which one or more of the 15 known serotonin
receptors on each brain cell play the biggest roles in depression. "Nobody knows which of the
serotonin receptors is being activated," says Dr. Molinoff. "If we home in on the specific
receptor, we'll automatically have a faster acting and more efficacious compound."
Pfizer, too, has found some apparently quicker-acting compounds. Later this year, at least one
will likely be in human clinical testing, says James Heym, Pfizer's group director of
neuroscience and general pharmacology. The 47-year-old Dr. Heim was a serotonin researcher
at Princeton University before joining Pfizer at its Groton, Conn., labs 15 years ago. At the
company, he was an early project manager on Zeldox, a schizophrenia drug Pfizer hopes to
market soon.
Pfizer is also exploring the possible involvement in depression of entirely different brain
chemicals, called neuropeptides. These are chains of amino acids that can also serve as chemical
messengers between cells.
One such chemical, called CRH, or corticotrophin-releasing-hormone, is found at relatively
higher levels among depression patients and suicide victims. Pfizer, among other companies, is
searching for a drug that would limit the effects of CRH on brain-cell receptors-and maybe
quickly uplift patients' moods because there might not be any built-in braking response.
SmithKline is moving into late-stage human clinical studies of a drug combination made up of
its Paxil and a generic cardiac drug called pindolol. In Spain and Canada, scientists have used
pindolol in combination with Prozac and Paxil to turbocharge the antidepressants. Research on
the combination elsewhere has produced mixed results, but both SmithKline and Lilly are
moving forward with the combined-drug approach.
Pindolol, aside from being a long established cardiac drug, also happens to be a drug that is an
"antagonist" of the 1A receptor that acts as a brake on the effects of serotonin. In effect, it's a
brake on the brake. But because it's a cardiac drug, pindolol also lowers blood pressure and the
heart rate and may be far from an ideal solution.
Along with the drug companies, various psychiatrists are experimenting on their own. Some get
quicker results for certain patients by combining the new drugs with older antidepressants called
tricyclics simultaneously. American Home Products Co.'s new antidepressant, Effexor, may
relieve depression in the first week in certain patients if they can tolerate very high doses of the
drug, company scientists report.
For many other patients, electro-shock treatment is the only fast-acting option. And oddly,
depriving a patient of approximately one night's sleep sometimes has amazingly quick effects in
countering a severe depressive episode. "Nobody knows why it works," says Lilly's Dr. Paul.
"But it does suggest to us that a quick response is possible."
Some technical obstacles make companies' new-drug research particularly difficult. One is the
fact that scientists haven't yet been able to design a depressed lab rat genetically. Thus, while
researchers can measure serotonin levels in rats' brains, they can't truly measure a drug's
behavioral effects on the rats. "We wouldn't recognize a depressed rat if we saw one," says
Lilly's Chris Fibiger, vice president of neuroscience research and discovery.
Some researchers also hope to be able to use high-tech "imaging" of depressed human patients'
brains to actually see if new compounds are changing brain chemistry. Right now, this
technology isn't advanced enough. But Harvard Medical School researcher Darin Dougherty
says he expects that imaging will soon play a significant role in exploring faster antidepressants. |
