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Biotech / Medical : Ligand (LGND) Breakout! -- Ignore unavailable to you. Want to Upgrade?


To: bob smith who wrote (13617)1/23/1998 12:23:00 AM
From: Henry Niman  Read Replies (1) | Respond to of 32384
 
bob, Speaking of nothing to say. LGND has had a problem getting info from PFE. Maybe it's because the info wasn't all that good. LGND's cancer royalty on Droloxifene for breast cancer was only 1%, so the switch to an osteoporosis emphasis may be be a plus (the Droloxifene royalty rate for that is 3%). PFE may also accellerate development CP-366,156, which LGND has indicated is better than Droloxifene and the royalty rate on CP-366,156 is 6%.



To: bob smith who wrote (13617)1/23/1998 12:27:00 AM
From: Henry Niman  Read Replies (1) | Respond to of 32384
 
bob, Speaking of cancer and SERMs, here's an intersting related item that may get AHP pushing TSE424 a bit harder:

Thursday January 22, 10:54 pm Eastern Time

Study may explain how estrogens cause cancer

By Maggie Fox, Health and Science Correspondent

WASHINGTON, Jan 22 (Reuters) - U.S. chemists reported on Thursday they had found a
by-product of Premarin, the top- selling menopause drug, which could explain why users have a
higher risk of cancer.

Reporting in Chemical Research in Toxicology, a journal of the American Chemical Society, they
said it damaged DNA in a way that could cause breast cancer and all estrogen replacement drugs
should be checked for the same effect.

The research team, led by Judy Bolton from the University of Illinois in Chicago, and the makers of
Premarin both described the findings as preliminary.

Manufacturer Wyeth-Ayerst, an American Home Products (AHP - news) subsidiary, said it
doubted the findings could be extended to women.

''While we have not yet had an opportunity to read the paper... the results of this study are very
preliminary,'' spokeswoman Audrey Ashby said.

''It is important to point out that the entire sequence of reactions hypothesized by the author are
highly unlikely and are not known to occur in women receiving estrogen replacement therapy.''

Bolton and her colleagues were trying to figure out why Premarin and other forms of estrogen
replacement therapy are associated with slightly higher rates of breast cancer.

They made a synthetic version of one of the components of Premarin, which is derived from the
urine of pregnant mares, and studied how it breaks down in a test tube.

They found this breakdown product, or metabolite, reacted in an unusual way with DNA -- the
body's genetic building blocks. Damage to DNA can cause cancer.

''If this reaction were to occur with DNA in breast cells, and that damage is not repaired, mutations
could result, leading to the initiation of the carcinogenic process in the breast,'' Bolton said in a
statement.

Bolton stressed that her team used a synthetic chemical and there was no evidence that Premarin or
any other estrogen broke down to make this particular metabolite in humans.

''Making the step from our study to the cell is a big step, let alone the step from the cells to the
animals to the person,'' Bolton said in a telephone interview. ''This is extremely preliminary work.''

She said the effect might extend to all estrogens.

''Estrogens are carcinogenic and it's known that the longer a woman is exposed to estrogen, the
higher her risk of developing cancer,'' Bolton said.

Cancer experts have long said a woman's higher risk of cancer that comes with hormone
replacement therapy (HRT) is the same as her risk would be if she had not gone through
menopause. In other words, the body's natural production of estrogen can be a cause of cancer
over time.

HRT decreases a woman's overall risk of death, greatly reducing the chance she will develop
osteoporosis and reducing the risk of heart disease -- which kills many more women than cancer
does.

Premarin is the number one prescribed drug in the United States, taken by 10 million women.
Worldwide sales in 1996 were $1.39 billion.

A newly approved drug may offer many of the benefits of HRT without the risks. Eli Lilly and Co's
(LLY - news) Evista, approved in December, is the first of a new class of drugs that fight thinning
bones and which might also help protect older women against heart disease.

The drug, known generically as raloxifene, works by mimicking the effects of estrogen in some parts
of the body -- for example its protective effects on bone -- while avoiding ''bad'' effects such as an
increased risk of cancer.

More Quotes
and News:
American Home Products Corp (NYSE:AHP - news)
Eli Lilly and Co (NYSE:LLY - news)

Related News Categories: health, medical/pharmaceutical

Thursday January 22, 10:54 pm Eastern Time

Study may explain how estrogens cause cancer

By Maggie Fox, Health and Science Correspondent

WASHINGTON, Jan 22 (Reuters) - U.S. chemists reported on Thursday they had found a
by-product of Premarin, the top- selling menopause drug, which could explain why users have a
higher risk of cancer.

Reporting in Chemical Research in Toxicology, a journal of the American Chemical Society, they
said it damaged DNA in a way that could cause breast cancer and all estrogen replacement drugs
should be checked for the same effect.

The research team, led by Judy Bolton from the University of Illinois in Chicago, and the makers of
Premarin both described the findings as preliminary.

Manufacturer Wyeth-Ayerst, an American Home Products (AHP - news) subsidiary, said it
doubted the findings could be extended to women.

''While we have not yet had an opportunity to read the paper... the results of this study are very
preliminary,'' spokeswoman Audrey Ashby said.

''It is important to point out that the entire sequence of reactions hypothesized by the author are
highly unlikely and are not known to occur in women receiving estrogen replacement therapy.''

Bolton and her colleagues were trying to figure out why Premarin and other forms of estrogen
replacement therapy are associated with slightly higher rates of breast cancer.

They made a synthetic version of one of the components of Premarin, which is derived from the
urine of pregnant mares, and studied how it breaks down in a test tube.

They found this breakdown product, or metabolite, reacted in an unusual way with DNA -- the
body's genetic building blocks. Damage to DNA can cause cancer.

''If this reaction were to occur with DNA in breast cells, and that damage is not repaired, mutations
could result, leading to the initiation of the carcinogenic process in the breast,'' Bolton said in a
statement.

Bolton stressed that her team used a synthetic chemical and there was no evidence that Premarin or
any other estrogen broke down to make this particular metabolite in humans.

''Making the step from our study to the cell is a big step, let alone the step from the cells to the
animals to the person,'' Bolton said in a telephone interview. ''This is extremely preliminary work.''

She said the effect might extend to all estrogens.

''Estrogens are carcinogenic and it's known that the longer a woman is exposed to estrogen, the
higher her risk of developing cancer,'' Bolton said.

Cancer experts have long said a woman's higher risk of cancer that comes with hormone
replacement therapy (HRT) is the same as her risk would be if she had not gone through
menopause. In other words, the body's natural production of estrogen can be a cause of cancer
over time.

HRT decreases a woman's overall risk of death, greatly reducing the chance she will develop
osteoporosis and reducing the risk of heart disease -- which kills many more women than cancer
does.

Premarin is the number one prescribed drug in the United States, taken by 10 million women.
Worldwide sales in 1996 were $1.39 billion.

A newly approved drug may offer many of the benefits of HRT without the risks. Eli Lilly and Co's
(LLY - news) Evista, approved in December, is the first of a new class of drugs that fight thinning
bones and which might also help protect older women against heart disease.

The drug, known generically as raloxifene, works by mimicking the effects of estrogen in some parts
of the body -- for example its protective effects on bone -- while avoiding ''bad'' effects such as an
increased risk of cancer.

More Quotes
and News:
American Home Products Corp (NYSE:AHP - news)
Eli Lilly and Co (NYSE:LLY - news)

Related News Categories: health, medical/pharmaceutical



To: bob smith who wrote (13617)1/23/1998 12:30:00 AM
From: Henry Niman  Read Replies (2) | Respond to of 32384
 
Here's the Droloxifene info:

Pfizer Shifts Droloxifene Development Program to Prevention of
Osteoporosis; Dofetilide Regulatory Filing on Schedule for First Quarter

Thursday, January 22, 1998 05:25 PM

> NEW YORK -- Pfizer Inc (NYSE:PFE) said today that due to interim clinical trial results, it is
shifting the focus of its developmental program for droloxifene, an estrogen agonist/antagonist, from
treatment of advanced breast cancer to prevention of osteoporosis.

Interim results from the world-wide clinical trial of droloxifene for the treatment of advanced
(metastatic) estrogen-receptor-positive breast cancer have shown that at the dose studied,
droloxifene offers no benefit beyond the current therapy. The company said that it will therefore not
submit the droloxifene New Drug Application (NDA) for treatment of breast cancer in the fourth
quarter of 1998 as originally anticipated.

Preliminary data regarding the efficacy and safety of droloxifene in osteoporosis, however, are
encouraging, especially when compared to currently available products, and Pfizer will now
accelerate development efforts in this therapeutic area. The company also plans to investigate the
use of droloxifene in the prevention of breast cancer and other potential health issues of
post-menopausal women.

Pfizer confirmed it will file an NDA with the U.S. Food and Drug Administration (FDA) for
dofetilide in March. Dofetilide is a selective potassium-channel blocker for the treatment of atrial
fibrillation (AF). Clinical data indicate that dofetilide is effective in controlling AF, a type of heart
arrhythmia, and is better tolerated than older drugs. More than 10 million patients worldwide suffer
from AF, which accounts for 15 percent of all strokes in the U.S. and can contribute to heart failure.

Approval of Viagra could come soon, the company said, noting that the NDA was filed in
September 1997, and FDA has granted it priority review. Pfizer is devising tactics to meet
anticipated high patient demand by accelerating the availability of the drug upon approval.

Viagra is a type 5 phosphodiesterase inhibitor for the treatment of erectile dysfunction (ED). It
works by blocking the activity of phosphodiesterase, an enzyme that inhibits blood flow to the
genital area. An estimated 140 million men worldwide (between 20 million and 30 million in the
U.S.) suffer from ED. Twenty clinical trials including 4,500 patients demonstrated high efficacy in
patients with organic, psychological or mixed ED.

Finally, the company said exploration of the anti-arthritic agent, tenidap, for possible future
development as a disease-modifying agent for osteoarthritis, has now been discontinued. Future
research will focus on back-up anti-arthritis compounds with potentially enhanced safety and
efficacy characteristics.

Pfizer Inc is a research-based, global health-care company. In 1997, the company reported
revenues of more than $12.5 billion and research and development spending of more than $1.9
billion.

/NOTE TO EDITORS: Pfizer's press releases are available at no charge through PR Newswire's
Company News On-Call fax service and on PRN's Web Site. For a menu of Pfizer press releases
or to retrieve a specific release, call 800-758-5804, extension 688250, or
prnewswire.com on the Internet.