Nice article in G&M today:
globeinvestor.com
AEterna in race to treat cancer
by Leonard Zehr - Monday, August 7, 2000
Toronto -- A metre-long dogfish shark plying the coastal waters of the Americas may hold
the key to a promising new approach in cancer treatment: choking off the blood supply that
feeds tumour cells so they die and can't spread through the body.
This biological process is called anti-angiogenesis, and it is being championed by AEterna
Laboratories Inc. of Quebec City. The company, which is using a substance found in shark
cartilage to find a treatment for cancer, is one of the front-runners in an international race to
win marketing approval for an angiogenesis blocker.
Winning, placing or showing in this race could produce a billion-dollar payoff in drug sales
to treat a disease that strikes one in three people and claims the life of one in six of them.
"We have a good chance to be among the top three regulated drugs in this field," said
AEterna founder and head Éric Dupont.
A report prepared last year by London's Financial Times Business Ltd. estimated that the
angiogenesis market is expected to grow from its current level of zero dollars to
$3.77-billion (U.S.) by 2005 on the strength of clinical trials with about 100 promising
agents.
"An estimated 184 million patients in the United States and European Union could benefit
from angiogenic inhibitors alone," the report said, citing management of cancer, diabetic eye
disease, arthritis, psoriasis and other disorders.
All of which is drawing attention to AEterna and its drug, Neovastat, which Mr. Dupont
helped invent in 1994.
The liquid extract from shark cartilage has already treated 540 cancer patients, some of
whom have been taking it for four years.
It has been used alone or in combination with other therapies and has come through early
stage clinical testing with flying colours for safety and tolerability.
AEterna is now enrolling patients in two pivotal Phase III trials that will determine whether
Neovastat -- developed at a cost of $42.6-million (Canadian) -- can effectively extend the
life span of patients with lung and kidney cancers. Results of the two studies, which
represent the final step before marketing approval, will be released during 2002.
In addition, AEterna will be meeting with U.S. Food and Drug Administration officials this
month to discuss starting a third Phase III clinical trial in oncology with Neovsatat.
"In the space of 10 years, AEterna has been able to take a drug from discovery to Phase III
on its own -- tackling a highly competitive field filled with heavy-hitters, which is almost
unprecedented for a small biotech company," said William Li, president and medical
director of the Angiogenesis Foundation in Cambridge, Mass.
Angiogenesis and its impact on cancer traces its roots back to the mid-1960s when Judah
Folkman, a surgeon at Harvard Medical School, suggested that tumour growth was
dependent on a network of blood vessels, and that without that blood supply tumours could
not grow beyond a certain size.
"The concept was considered heretical at the time," recalled Dr. Li, who trained in Dr.
Folkman's lab.
But research in the 1980s corroborated Dr. Folkman's work as scientists identified several
molecules called growth factors that are sent out by cancer cells in order to begin the
angiogenic process of forming blood vessel cells.
Today, researchers believe there are at least 20 of these growth factors produced not only by
healthy cells for normal functions, such as tissue healing and growth, but also by a variety of
diseases that can overwhelm the body's natural defense systems.
The Angiogenesis Foundation estimates that about 200 biotechnology, genomics,
pharmaceutical and medical device companies are conducting research into angiogenesis
inhibitors, with about 80 per cent of the work aimed at finding treatments for cancer.
AEterna's success stems largely from research by Robert Langer and Ann Lee at the
Massachusetts Institute of Technology in the early 1980s. They suggested that shark cartilage
contains a substance that significantly inhibits the development of blood vessels, which
nourish tumours and facilitate their spread to form secondary tumours, or metastasis.
That discovery spawned a multimillion-dollar industry peddling powdered shark cartilage
as a miracle cure for cancer, first in health food stores and now over the Internet. The
reason: Sharks don't get cancer. But claims of the powder's power are "bull," Mr. Dupont
said. "There is no biological activity in shark cartilage powder."
On the other hand, AEterna contends that Neovastat is the only compound in Phase III trials
that blocks the two main chemical processes of angiogenesis: matrix metalloproteinases
(MMPs), which are enzymes that open the walls of blood vessels; and proteins such as
vascular endothelial growth factor (VEGF) that enable blood vessel cells to move to the site
of disease.
Nevertheless, Mr. Dupont has spent years countering skeptics not only about his clinical
approach with shark cartilage, but also about the entire angiogenesis field itself.
That began to change when companies such as Bristol-Myers Squibb Co., Warner-Lambert
Co., Bayer AG and Genentech Inc. began developing angiogenesis inhibitors.
Then in 1999, Warner-Lambert paid $2.1-billion to acquire Agouron Pharmaceuticals Inc. of
San Diego and Pharmacia & Upjohn Inc. paid $650-million to buy Sugen Inc. of San
Francisco. Agouron and Sugen are both in Phase III tests with their angiogenic blockers to
treat cancer.
AEterna's Phase III trial in lung cancer, which is being sponsored by the U.S. National
Cancer Institute, has been designed to determine whether Neovastat can extend patients'
median survival by a minimum of 25 per cent.
Mr. Dupont explained that lung cancer patients in the trial receiving a placebo,
chemotherapy and radiation should survive 12 to 13 months. For the study to be successful,
patients taking Neovastat will have to survive four months longer, or a total of 17 months,
than those on the placebo.
In the kidney trial, patients receiving Neovastat will have to survive for about 12 months,
compared with the estimated eight-month survival of patients getting the placebo. |
