The point is Novartis spent nearly $1Billion on this technology.
Dramatically more than the pittance the US government is proposing and we
keep drooling over.  Let's face it.  If you want anything done, the
government is not the place to look.

Larry Fleming
54/51
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http://homepages.msn.com/HobbyCt/flemco

-----Original Message-----
From:   Parkinson's Information Exchange Network
[mailto:[log in to unmask]] On Behalf Of Nita Andres
Sent:   Thursday, October 28, 1999 1:57 PM
To:     [log in to unmask]
Subject:        Re: Gene Therapy

Janet, more on Novartis and gene therapy. How much time do drug companies
spend
on developing drugs before they throw in the towel?  Really strange, it
seems to
me that it would take a lot of time. Love, Mother

Flemco- wrote:

> Researchers Get Dose of Reality
> As Logistics Stymie Gene Therapy
> By ROBERT LANGRETH and STEPHEN D. MOORE
> Staff Reporters of THE WALL STREET JOURNAL
> Eight years ago, Swiss drug maker Sandoz AG was dazzled by a tiny U.S.
> biotechnology firm doing promising work in the new field of gene therapy.
> Genetic Therapy Inc. and government scientist French Anderson, its
> co-founder, claimed that injecting healthy genes into the body to replace
> damaged or defective ones would revolutionize medicine by letting doctors
> attack the causes of diseases such as cancer and cystic fibrosis, rather
> than just the symptoms.
> Sandoz, which would merge with Swiss rival Ciba-Geigy AG in 1996 to form
> Novartis AG, bought into this bold new vision. It began amassing GTI
shares
> in 1991; in 1995, it bought the Gaithersburg, Md., company outright,
> bringing its total investment in GTI to more than $300 million. By 1997,
> Sandoz, looking for new technologies to fuel its profits, also had
invested
> $548 million to acquire SyStemix Inc., which was developing a related
> process.
> These days, however, gene therapy looks unlikely to pay off in a big way
> anytime soon. And Novartis is scrambling to salvage its nearly $1 billion
> investment in the technology. All but one of the human gene-therapy
testing
> programs once under way at GTI and SyStemix have been scrapped or
> temporarily halted. And none of the hundreds of human studies conducted
> elsewhere around the globe so far have offered clear proof that gene
therapy
> works in any significant way to fight disease.
> "This has been an overhyped area that has failed to reach its promise for
> very obvious technical reasons," says George Poste, a top research
executive
> at British pharmaceutical maker SmithKline Beecham PLC.
> 'We Were Naive'
> Even Dr. Anderson has tempered his enthusiasm. "We were naive to think we
> could revolutionize medicine in 10 years," says the researcher, who now
> doubts that major gene-therapy drugs will reach the market before 2004 or
> 2005.
> Indeed, the sudden death last month of a patient undergoing experimental
> treatment for a rare liver disorder at the University of Pennsylvania --
the
> first death apparently linked to gene therapy -- has raised questions
about
> whether scientists have been in too big a hurry to test such therapy on
> humans. As a precaution, federal regulators since have ordered U.S. drug
> maker Schering-Plough Corp., which wasn't involved in the University of
> Pennsylvania research project, to temporarily stop enrolling new patients
in
> certain gene-therapy trials for cancer.
> Back in 1990, though, gene therapy was generating enormous excitement. Dr.
> Anderson and his colleagues at the National Institutes of Health treated a
> young girl with a rare and potentially fatal immune disorder called ADA
> deficiency, or "boy-in-the-bubble" disease. Dozens of hospitals and
medical
> schools sought government approval for human trials for other illnesses.
> Boosters went so far as to predict that the first gene therapies would hit
> the market as early as 1996.
> Sandoz, one of the pharmaceutical industry's most aggressive investors in
> the new field, had high hopes of using gene therapy to treat the deadliest
> form of brain cancer, glioblastoma, and other cancers. But in 1998,
Novartis
> quietly abandoned its flagship gene-therapy project after a large-scale
> human test failed to prove that the therapy was effective. And, earlier
this
> year, the drug maker undertook a painful overhaul of its entire
gene-therapy
> research program. Now, Michael Perry, who has run both GTI and SyStemix
> since their operations were combined last fall, says no new human tests
are
> planned until a host of technical issues are resolved.
> A Crucial 24 Months
> "Novartis is not proud of it right now," Dr. Anderson says of the program.
> "Something has got to show up on the radar screen in the next 24 months or
> some really serious decisions are going to be made" says the researcher,
who
> serves on GTI's board and is now a University of Southern California
medical
> school professor.
> Even so, Novartis Chief Executive Daniel Vasella says his company remains
> committed to the field. "There isn't a single major drug on the market
that
> hasn't been close to the grave at some point," he says. If gene therapy
> ultimately fails to produce a major product, "I'd still say fair enough.
> That's our business. If you don't spend big money and take big risks, you
> shouldn't be in the pharmaceutical industry," adds Mr. Vasella, who notes
> that gene therapy accounts for a small fraction of Novartis's annual
> health-care research budget of more than $2 billion.
> >From the beginning, the therapy's main difficulty has been a logistical
one:
> how to deliver enough healthy genes to the appropriate site and get them
to
> stay there long enough to cure or alleviate a disease. For example,
> researchers estimate that to cure cystic fibrosis, a hereditary
respiratory
> disorder, new genes would have to be permanently placed in a billion
> defective cells in the lung's airways. Researchers often use genetically
> engineered viruses as vehicles for such genes. For example, an adenovirus
> was used as the carrier in the University of Pennsylvania trial in which
the
> patient died. But the technique has its drawbacks: Sometimes a patient's
> immune system, wary of foreign invaders, tries to fight off the viral
> vehicles. To be sure, gene-therapy researchers recently have made progress
> in some areas, such as treating heart disease or hemophilia. But overall,
> the therapy's short-term applications seem narrower than they did a few
> years ago.
> Confident of a Breakthrough
> After Sandoz and GTI began working together in November 1991, GTI
scientists
> were confident of achieving a breakthrough. The feeling was: "We are going
> to do something very important here," says Alan McClelland, a former GTI
> research manager now at rival Avigen Inc.
> GTI's showcase gene-therapy effort, aimed at treating glioblastoma, was
> conceived by colleagues of Dr. Anderson at NIH. It involved inserting
> so-called suicide genes into the DNA of tumor cells to make them sensitive
> to the antiviral drug ganciclovir; doctors could then give patients the
> antiviral to kill the tumor cells.
> The first human test was conducted in the early 1990s at the NIH, with GTI
> as a partner. Initial results seemed highly encouraging. The first
patient's
> tumor shrank dramatically following the treatment. Although distant tumors
> eventually killed him eight months later, the original tumor never came
> back. A second patient showed no response. A third patient's tumor also
> shrank significantly, though only temporarily. Overall, the tumors of six
of
> the 15 patients studied showed some shrinking in response to the therapy;
in
> one case, the tumor disappeared entirely and the patient seemed to fully
> recover, a rare outcome in glioblastoma.
> GTI executives didn't wait for all the data to come in before they began
> planning a second test on a few dozen patients at the University of
> Washington and elsewhere. But even as these new tests were launched,
Edward
> Oldfield, an NIH neurosurgeon, was analyzing the results of the first
trial,
> which he had led, and he was growing increasingly skeptical of the
therapy.
> It seemed the new genes penetrated only a tiny fraction of tumor cells in
> the immediate vicinity of the injection. While this killed nearby cancer
> cells, a phenomenon dubbed "the bystander effect," it seemed to have no
> impact on cells farther afield. And Dr. Oldfield wasn't convinced that the
> one patient's recovery was fully a result of the gene treatment.
> "We didn't think it had enough activity to be meaningful. Based on what we
> had seen, I saw no hope of distributing the gene where it needed to go,"
> says Dr. Oldfield, a surgical chief at the National Institute of
> Neurological Diseases and Stroke.
> By 1994, Sandoz had decided to expand its collaboration with GTI to
include
> the glioblastoma work. It started its own small human test in Europe. The
> initial results were mixed, and oncologist Athos Gianella-Borradori, the
> Sandoz official helping coordinate the trial, says he had doubts the
> treatment would work. He says he told his superiors at Sandoz and
officials
> at GTI of his reservations, aware they might be interpreted "as a betrayal
> of our cause."
> He had another concern: By late 1995, several prominent gene-therapy
trials
> elsewhere had failed, leading some to question the validity of the entire
> approach. Dr. Gianella-Borradori, who left Sandoz a few years ago and now
> works at Bavarian Nordic GmbH in Germany, says he didn't want another such
> failure.
> That same year, an NIH committee set up to review gene therapy concluded
> that problems remained "in all basic aspects" of the technology. Top
> researchers were reporting disappointing results. Scientists at the
> University of North Carolina in Chapel Hill disclosed that a trial for
> cystic fibrosis produced side effects and didn't alleviate the disease.
> Another trial, at Ohio State University, found that a muscular-dystrophy
> treatment didn't improve muscle strength.
> Still, GTI and Sandoz forged ahead. Although gene therapy affected only a
> limited number of cancer cells directly in the glioblastoma project,
Sandoz
> was impressed by the fact that a handful of patients in the various trials
> appeared to be among the rare long-term survivors of the disease.
> Researchers theorized that the new genes had triggered an immune response
> against the cancer. A neurosurgeon who led the University of Washington
> trial says he was so taken by his results that he flew to Switzerland, to
> urge Sandoz to continue the program.
> Comparative Study
> In 1996, Sandoz, soon to become Novartis, launched a large trial that
would
> compare the effectiveness of gene therapy combined with standard treatment
> to that of standard treatment alone. It would be by far the largest
> gene-therapy trial to date, with more than 200 patients.
> Novartis development chief Joerg Reinhardt says the company was fully
aware
> of the high risk of failure. But given the reports of patients who seemed
to
> respond to treatment, Novartis felt larger brain-cancer trials were in
> order. The test began in the summer of 1996 at hospitals in Europe and the
> U.S.
> Meanwhile, GTI's gene-therapy treatments for other diseases were running
> into problems. When Sandoz bought it out in August 1995, GTI was involved
in
> early-stage human tests of therapies for cystic fibrosis, breast cancer
and
> several rare genetic diseases. But these efforts were halted, one by one,
as
> it became clear that existing gene-delivery technology couldn't deliver
> enough genes to do the job. Novartis says Sandoz wasn't counting on any of
> these preliminary tests to succeed when it bought GTI.
> Different Concepts of Time
> As project after project stumbled, Novartis grew worried that GTI's
approach
> was too scattered. There were "too many things going on, and not enough
> focus," says Paul Herrling, Novartis's research director. Novartis
attempted
> to impress its deliberate decision-making style on GTI, but ended up
> frustrating some researchers there. A running joke was that at GTI the
clock
> ticked in days, but at Novartis it ticked in quarters. Dr. Herrling says
> there were clashes. "We had no experience with this biotechnology; they
had
> no experience with drug development."
> In another setback, the U.S. Federal Trade Commission, reviewing the
> proposed Sandoz-Ciba merger in 1996, demanded -- as a condition for
> approving the deal -- that rights to key GTI patents be offered to rival
> companies. Sales of gene-therapy drugs, the FTC predicted, could reach $45
> billion a year by 2010 -- a figure that today seems highly unrealistic.
> By early 1998, preliminary results of the large-scale comparative trials
on
> brain-cancer patients were rolling in. They didn't look good. Patients who
> underwent gene therapy didn't live longer than those receiving standard
> treatment. For Novartis, it was the final straw.
> Returning a Verdict
> In mid-1998, the panel of scientists that reviews Novartis's research each
> year took a hard look at gene therapy. Its verdict: Improved gene-delivery
> methods were needed in order to give human tests a better chance of
success.
> Soon thereafter, Novartis combined GTI and SyStemix. Many GTI officials
were
> shocked when GTI bore the brunt of the cuts, which included most of GTI's
> senior managers for drug development. Roughly 90 employees, or about 20%
of
> the two units' combined staffs, were laid off, the vast majority of them
at
> GTI. Mr. Perry, a Novartis insider who had been running SyStemix for more
> than a year, was chosen to head the combined operation from SyStemix's
Palo
> Alto, Calif., laboratory. The decision, Mr. Perry says, didn't reflect on
> the quality of GTI's researchers.
> Dr. Anderson sees it differently. GTI was "charging off in various
> directions" and not always conforming to Novartis's corporate goals.
> Novartis had tried to rein in the company, but "wasn't successful."
> Novartis has since scaled back or eliminated many gene-therapy research
> projects. "It is not on my high priority list to go into the clinic now,"
> Mr. Perry says. But he says he is "positive" that gene therapy will play a
> major role in medicine, and that Novartis's past experience will give it
an
> edge. "Certainly, there is pressure" to produce a return on Novartis's
> investment, he says. "It is a question of when, not if."
>
> Larry Fleming
> [log in to unmask]
> http://homepages.msn.com/HobbyCt/flemco