W, The market may have responded late Friday because they heard that WSJ would be coming a designer estrogen article this morning:
April 20, 1998
New Drugs Give Cause for Hope
In Battle Against Breast Cancer
By THOMAS M. BURTON
Staff Reporter of THE WALL STREET JOURNAL
Earlier this month, women at risk of developing breast cancer received a
limited reason for hope: A drug called tamoxifen was found effective at
preventing breast cancer, but it is associated with increased rates of uterine
cancer.
Now comes a potentially bigger breakthrough. As-yet-unreleased results
of clinical trials of a drug called Evista indicate that it, too, is effective at
preventing breast cancer-without any increase in the risk of uterine cancer.
Trials of Evista as a cancer combatant go back only two years-too short a
time to elicit anything more than very cautious optimism from scientists,
and skepticism from some health officials. "Two years is nothing," says
Cynthia A. Pearson, executive director of the National Women's Health
Network, a consumer group. What is known about the drug "can change
in five years or 10 years."
Designer Drugs
Yet whether or not tamoxifen and Evista become widely used
breast-cancer weapons, their performance in clinical trials is prompting
some researchers to envision a turning point in the battle against several
cancers. In the minds of some top researchers, prevention with
pharmaceuticals, as opposed to conventional treatment after diagnosis, is
becoming a real possibility.
"We're entering a new period in which we may have the ability to consider
and test drugs to lower the incidence of cancers the way we lower
cholesterol," says Richard D. Klausner, director of the National Cancer
Institute. Calling Evista and other such drugs "the beginning of the era of
designer hormones," he adds, "we need to enter into this new era very
cautiously."
Caution is difficult because the stakes are so high. This year, breast cancer
alone will strike an estimated 178,000 women in the U.S. and kill 43,500
--some of them genetically predisposed to the cancer. Millions of others
live in fear of it, so that even the most guarded talk of a prevention pill is
bound to raise hopes-and not only among potential sufferers.
Market Impact
Although the maker of Evista, Eli Lilly & Co., has tried to keep its
clinical-trial results under wraps, The Wall Street Journal and at least one
securities analyst have obtained some of the data. On Friday, after
Morgan Stanley analyst Paul Brooke wrote about some of the highly
promising Evista results, investors immediately drove shares of Lilly up
$5.125, to close at $68.375 in composite trading on the New York Stock
Exchange.
Many researchers share that excitement. After all, the news about
raloxifene, the generic name for Evista, is coming only days after tamoxifen
was declared the first drug in history to be able to prevent new breast
cancers, at least over a four-year period.
"I'm excited about" raloxifene, says Funmi Olopade, oncologist and
director of the cancer-risk clinic at the University of Chicago Medical
Center. "My take on raloxifene is that it may be an improvement over
tamoxifen. This means there are going to be more options for women."
Both Evista and tamoxifen belong to a class of drugs known as selective
estrogen receptor modulators, or SERMs. These drugs, sometimes called
designer estrogens, have been developed to replace traditional estrogen
therapy. That therapy strengthens bones, improves cardiac health and is
believed to provide some protection against Alzheimer's disease. But in
older women, it also is associated with an increase in the incidence of
uterine cancer and possibly of breast cancer. Even so, the leading
estrogen-replacement therapy for older women, American Home Products
Co.'s Premarin, is a $1 billion-a-year drug.
Only the Good Stuff
The SERM drugs are meant to achieve the positive effects and avoid the
dangerous ones. Among the companies with such drugs in their pipelines
are Glaxo Wellcome PLC, Pfizer Inc., SmithKline Beecham PLC and
Zeneca Group PLC, which sells tamoxifen under the brand name
Nolvadex.
In Indianapolis, Lilly officials decline to talk about Evista as a
breast-cancer combatant. They can't. Because Evista is approved
currently as a drug only for osteoporosis, Lilly isn't allowed to say anything
publicly suggesting that Evista reduces breast-cancer risk. The company
and its sales representatives are allowed to say only that Evista doesn't
increase breast cancer, and that it increases bone density and thus helps
prevent osteoporosis in older women.
But certainly, Lilly officials would love to see Evista become the Prozac of
the breast-cancer battle. Early next century, the patent on Lilly's leading
product, the antidepressant Prozac, will expire, and Lilly needs something
to replace it. It has a good start with Zyprexa, which in just 18 months on
the market has become the No. 1 schizophrenia treatment, with estimated
sales this year of more than $1 billion.
But Prozac will rack up sales this year of an estimated $2.8 billion, and
Lilly will probably need more than one drug to replace it.
As an osteoporosis preventive, Evista had estimated sales of $30 million in
its first full quarter on the U.S. market, ended March 31. But its most
promising use has been quietly under study at University of California at
San Francisco, Northwestern Memorial Hospital in Chicago and
Memorial Sloan-Kettering Cancer Center in New York, among other
locations.
The Evista trials pose the same question as the tamoxifen trials: Can this
drug prevent breast cancer?
Big Groups
The trials of tamoxifen, a failed contraceptive that had proven effective at
treating breast cancer, lasted four years. These trials showed that in
healthy women at high risk of breast cancer, tamoxifen lowered the
incidence of the disease by 45%, compared with women who had taken a
placebo. The tamoxifen trials involved a large number of women, 13,338,
and the Evista trials even more, about 19,000.
The Evista trials don't provide a solid comparison. The Evista work has
been conducted on a general population of women who have gone through
menopause and who don't necessarily have a higher cancer risk. And the
Evista trials, which are continuing, have been going on for about half as
long.
But the results so far could hardly be more promising. In one trial, UCSF
physician Steven R. Cummings recorded a "relative risk" of breast cancer
of 0.26 in women who took Evista compared with a control group. That
means a reduction in the incidence of new breast cancers of about 74% in
the women who took Evista over an average of two years and five
months.
During the study, twice as many women were given Evista as those in a
control group, who received only a placebo. Yet only 11 of the women on
Evista, or 0.21%, had new breast cancers confirmed during the study.
Meanwhile, 21 of the women assigned to placebo, or 0.82%, got new
breast cancers. Dr. Cummings declined to discuss the results.
In the tamoxifen trials, users developed uterine cancer at more than twice
the rate of placebo takers. In the Evista trials, users had a lower rate of
uterine cancer than those who took placebos.
A head-to-head comparison of Evista and tamoxifen is expected to begin
in the fall, under the direction of the National Cancer Institute. But already,
the evidence that drugs can be designed to protect organs from
cancer-inducing hormones is exciting some usually reserved scientists.
"The tamoxifen and Evista studies represent one of the biggest
breakthroughs in cancer research in history," says Larry Norton, director
of the breast center and head of medical oncology at Memorial
Sloan-Kettering.
Next: Prostate Cancer
"If we can convert the breast into an organ that isn't responsive to
[cancer-inducing] estrogen, we could reduce breast cancer by 99%," says
Dr. Norton, a key researcher in the Evista trials. "And breast cancer isn't
the only one. The next one to go is prostate cancer."
Lilly divided its trials into one group of about 7,000 patients and another
group of about 12,000. The full results of both clinical trials will be
presented at an American Society of Clinical Oncology symposium next
month in Los Angeles. The presentation will likely answer some vital
questions: Were the ages and general health of the Evista group precisely
comparable with those in the control group? How serious and frequent
was the one known big side effect of Evista -- a rare form of blood clots?
And only time will answer the biggest question: Does Evista lower cancer
risk permanently or simply delay new tumors for a couple of years?
Among its other lethal qualities, experts note, cancer is patient. Says Ms.
Pearson of the National Women's Health Network: "I wouldn't trust a
drug to reduce breast cancers without 10 years of data." |
