I just found another mention of Idec, off the XOMA thread on SI (message #747)...
George and All,
An article of some significance regarding E5 (Murine mAB) and FYI. Read the entire article and consider that
today most murine antibody products are humanized prior to use in the clinic. OK?
Monoclonal Antibodies Make a Comeback
(1/7)
By Dane Hamilton
c.1997 Bloomberg Business News
LONDON -- Science that won Britain a Nobel Prize in 1984 may soon pay off in a big
way for Celltech Group Plc, a British biotechnology company that was formed to exploit
technology from the U.K.'s rich science base.
The company is well-positioned to be among the first to market a new generation of
drugs based on genetically engineered proteins, a major advance in biotechnology in the
last 20 years.
They are called monoclonal antibodies, once dubbed ``magic bullets,'' a 1974 discovery
that failed to live up to early promise as a potential cure for cancers, viruses and a range
of other diseases.
Now, years after optimism has waned, monoclonal antibodies are making a comeback --
and showing potential to generate millions of dollars for drug and biotech companies like
Berkshire-based Celltech, Germany's Bayer AG, and in the U.S., Idec Pharmaceuticals
Corp., Centocor Inc., Genentech Inc. and Protein Design Labs Inc.
``It's incredibly encouraging, just unbelievable,'' said Thomas Geimer, a Henry Cooke,
Lumsden Plc analyst, of Celltech's latest clinical trial of its monoclonal antibody drug.
Called CMA-676, the drug virtually obliterated acute myeloid leukemia in two patients in
a 36-patient study released last month with its partner, U.S. drugs-maker American
Home Products Corp.
It remains to be seen whether the Celltech compound will pass later tests and work over
time against the deadly blood disorder. But Geimer said the trial results ``prove that
monoclonal antibodies are going to start to come back.''
Monoclonal antibodies were discovered in Britain in 1974 by University of Cambridge
scientists Cesar Milstein and Georges Kohler, who won the Nobel Prize a decade later
for their work.
The scientists developed a way to fuse cancer cells with antibody cells, creating a new
cell that had both the disease-fighting potential of antibodies and the rapid replication
properties of cancer cells. The fusion was done with mouse cells, widely used in
medicine because they mimic the properties of human cells.
The Milstein-Kohler discovery was hailed as a major advance in biotechnology, a new
field that was then beginning to flower in Boston and California following the
ground-breaking discoveries in genetics by James Watson and Francis Crick at
Cambridge in 1953.
Discoveries in cell fusion, gene-cloning and recombinant DNA became the founding
technologies for companies like South San Francisco-based Genentech Inc., Cambridge,
Massachusetts-based Biogen Inc. and a host of other early biotechnology companies.
Scientists theorized that billions of cloned antibodies could be injected into patients with
cancer, deadly viruses, bacterial infections or other conditions where the immune system
needed a major boost.
Unfortunately, while early mouse antibodies worked well in theory, they didn't in
humans.
Now Celltech, Mountain View, California-based Protein Design Labs and San Diego,
California-based Idec could be on the verge of a breakthrough in tests of new
monoclonals that are generations beyond the originals.
Not only are the new drugs almost identical to human antibodies, they can be loaded with
``warheads'' of cytotoxic, or cell-killing, drugs and trained to hone in on cancer cells,
like heat-seeking missiles.
``There's more of a general mood that suddenly antibodies are proving much more
versatile than ever thought previously,'' said David Bloxham, research and development
director for Celltech, based in Slough, England. ``In the late `80s, people were sick to
death of them. Everyone had gone up a blind alley where it seemed there was no future to
them.''
To be sure, monoclonals have had moderate successes, including Johnson & Johnson's
Orthoclone OKT3, used to prevent kidney transplant rejection, and Glaxo Wellcome's
Panorex, a colorectal cancer treatment, now sold only in Germany.
The latest addition to the market, Centocor's ReoPro, better reflects hopes for new
generation monoclonals in treating such conditions as cancer, septic shock, rheumatoid
arthritis and other major diseases, analysts say.
``After a decade and a half of experience, people have figured out what situations they are
going to be useful in,'' said Rachel Leheny, a biotechnology analyst with Hambrecht &
Quist, which specializes in emerging technology stocks.
ReoPro, developed by Malvern, Pennsylvania-based Centocor and sold by Eli Lilly and
Co., acts to stop blood clots from forming in patients that have had balloon angioplasty, a
treatment to open clogged, blood vessels to the heart. Launched a year ago, the drug is
likely to generate $140 million this year, and some analysts predict it could generate as
much as $600 million by 1999, a major seller by industry standards.
Other kinds of monoclonals hitting the market in the next three years could dramatically
expand this sales. They include potential treatments for rheumatoid arthritis and
inflammatory bowel disease from Celltech and Centocor, potentially a
billion-dollar-a-year market. Protein Design Labs is in late-stage testing of Zenapax, a
treatment for kidney transplant rejection, while Idec is in advanced testing of a treatment
for lymphoma, a deadly cancer.
Farther down the road are treatments from New York-based ImClone Systems Inc. and
others that are targeted at ``solid tumor'' cancers like breast, ovarian and lung cancers.
Such drugs could be huge sellers, analysts say. Celltech's Bloxham estimates that there
could be five or more additional monoclonal antibody treatments on the market by the
year 2000, and many more to come after that. If the efforts of a dozen or more
drugmakers working on monoclonals pay off, the future for such treatments is almost
limitless, said Bloxham.
``I think you could approach almost any disease through this route,'' said Bloxham.
Not everyone is as optimistic. Celltech's treatment for leukemia, a disease that kills most
of the 30,000 patients suffering from it each year, could fail, as have others in late-stage
testing.
Trevor Jones, former Wellcome Plc director of research and development, said he
directed clinical trials of a novel monoclonal antibody treatment for arthritis several years
ago. The drug eliminated the disease only to cause severe side effects.
``I eliminated arthritis in two patients, but gave them immune deficiency disease,''
lamented Jones, now director of the Association of British Pharmaceutical Industries, a
trade group.
Jones said monoclonals ``will be part of the next generation of cancer drugs, but it's fair
to say there will be more failures.''
And there have been some well-publicized failures, including septic shock drugs made by
Centocor and Xoma Inc., a California biotechnology company. That hasn't stopped
companies from exploring what may be a rich vein of new drugs.
``We've seen a few high-profile failures,'' said Nick Woolf, a biotechnology analyst
with Nomura International in London, who said monoclonals now underpin the largest
number of biotechnology products under development.
Still, Woolf has high hopes that the new generation of monoclonals will bear fruit.
``Conceptually, it's a great idea,'' he said.
Best,
Greg |
