Alzheimers & Spirochetes (NYT and the failed Eli Lilly Trial)
Mort Zuckerman
lPick...@cdc.gov, Durlan...@yale.edu, Aa...@columbia.edu,
gary_w...@nymc.edu, scientifi...@ostp.gov,
pkru...@princeton.edu, Stanle...@fiu.edu,
emcsw...@niaid.nih.gov, afa...@niaid.nih.gov,
Spin...@yahoogroups.com, kshe...@calea.org, fit...@gmail.com,
patrick.f...@usdoj.gov, model...@sbcglobal.net,
jdr...@nejm.org, let...@courant.com, Jgerb...@cdc.gov,
michae...@po.state.ct.us, con...@po.state.ct.us, executive-
edi...@nytimes.com, managin...@nytimes.com, news-
ti...@nytimes.com, biz...@nytimes.com, for...@nytimes.com,
nati...@nytimes.com, dv...@cdc.gov, brigidc...@optonline.net,
tr...@hotmail.com, illino...@aol.com, jle...@courant.com,
tinaj...@yahoo.com, jhorn...@fff.org, thomas...@usdoj.gov,
thoma...@po.state.ct.us, kur...@washpost.com,
georg...@washpost.com, p...@allegorypress.com,
commissi...@po.state.ct.us, brans...@comcast.net,
vts...@comcast.net, o...@po.state.ct.us, freet...@charter.net,
scott....@po.state.ct.us, govern...@po.state.ct.us,
attorney...@po.state.ct.us, randall...@usdoj.gov,
Robert....@yale.edu, edi...@greenwich-post.com,
harol...@yale.edu, sedm...@nswbc.org, rrmcg...@aol.com,
fr...@nytimes.com, dpr...@stmartin.edu, saint....@sbcglobal.net
Cc: fra...@ucia.gov, dr-ahma...@president.ir,
eugener...@washpost.com, afa...@niaid.nih.gov,
bmi...@newstimes.com, tr...@hotmail.com, rast...@aol.com,
billc...@gmail.com, amcg...@rms-law.com, rjmu...@aol.com,
paulcrai...@yahoo.com, criminal...@usdoj.gov,
karla.d...@usdoj.gov, christophe...@usdoj.gov,
richar...@yale.edu, harol...@yale.edu, james.p...@yale.edu,
inq...@aldf.com, ly...@idsociety.org, meganm...@theatlantic.com
Subject: Alzheimers & Spirochetes (NYT and the failed Eli Lilly Trial)
Date: Aug 18, 2010 7:30 AM
NYT Article below
=======================
Far be it from me to suggest
that BigPharma and the DHHS
take a reality approach:
http://www.actionlyme.org/BRAIN_PERMANENT.htm
Journal Article #22:
Molecular and immunological evidence of oral Treponema in the human
brain and their association with Alzheimer's disease.
http://www.ncbi.nlm.nih.gov/pubmed?term=11929559[uid]&cmd=DetailsSearch
The purpose of this investigation was to use molecular and
immunological techniques to determine whether oral Treponema infected
the human brain. Pieces of frontal lobe cortex from 34 subjects were
analyzed with species-specific PCR and monoclonal antibodies. ***PCR
detected Treponema in 14/16 Alzheimer's disease (AD) and 4/18 non-AD
donors (P < 0.001), and AD specimens had more Treponema species than
controls (P < 0.001). PCR also detected Treponema in trigeminal
ganglia from three AD and two control donors. Cortex from 15/16 AD
subjects and 6/18 controls contained Treponema pectinovorum and/or
Treponema socranskii species-specific antigens (P < 0.01).*** T.
pectinovorum and/or T. socranskii antigens were also found in
trigeminal ganglia and pons from four embalmed cadavers, and 2/4
cadavers also had Treponema in the hippocampus. These findings suggest
that oral Treponema may infect the brain via branches of the
trigeminal nerve.
==============
http://www.nytimes.com/2010/08/18/business/18lilly.html?_r=1&hpw=&pagewanted=print
August 17, 2010
Lilly Stops Alzheimer’s Drug Trials
By DUFF WILSON
Eli Lilly halted two late-stage clinical trials of an experimental
Alzheimer’s treatment on Tuesday, representing a setback to one
leading theory on treating the degenerative disease and a new blow to
Lilly’s business prospects.
The company said patients who had taken the drug, intended to reduce
plaque in the brain, actually showed worse cognitive functioning and
less ability to perform daily living tasks than patients who had taken
a placebo.
“A completely unexpected result,” Dr. Eric R. Siemers, medical
director for the Alzheimer’s team at Lilly, said in an interview. The
patients also had a higher risk of skin cancer. The trials involving
the drug, semagacestat, began in 2008.
The price of shares in the company, which is based in Indianapolis,
has fallen 5 percent in the last week, as Lilly has had problems
involving some of its most popular drugs.
Lilly officials said that they would still follow the more than 2,600
Alzheimer’s patients in 31 countries who were enrolled in the trials
for six more months. The company is conducting a separate test of a
biologic therapy aimed at Alzheimer’s.
Dr. Ronald C. Petersen, director of the Alzheimer’s Disease Research
Center at the Mayo Clinic in Rochester, Minn., and a member of the
executive committee of the Alzheimer’s Association, said the drug
failure highlighted the need to try to attack multiple targets related
to dementia, not just plaque on the brain. He compared the approach to
developing several drugs for hypertension.
“When one like this fails, it’s discouraging to the field, but it’s
not the end of the day,” Dr. Petersen, who was not involved with the
trials, said in an interview. “We have other targets out there and
other ways to attack the same target.”
Still, Lilly’s announcement quashed one hope, and an effective
prevention or cure, if possible, remains years away.
While hundreds of drugs are under study, Lilly’s effort was one of
only five to reach late-stage clinical trials, said Dr. Paul S. Aisen,
director of the federally financed Alzheimer’s Disease Cooperative
Study and a professor of neuroscience at the University of California,
San Diego.
“It is a significant disappointment,” he said, “but there’s still a
lot to be optimistic about.”
Dr. Aisen, who also consults widely for the drug industry, said he was
excited about brain scans and spinal fluid tests that may help to
identify people most at risk of Alzheimer’s before they show any
symptoms — the time a treatment may be most effective.
Lilly shares fell 2.3 percent to $34.75 on Tuesday, the latest of
several blows to the company. Lilly said it would charge 3 cents to 4
cents a share against third-quarter earnings for the Alzheimer’s test
failure but reaffirmed earlier guidance for 2010 profits.
“We are clearly disappointed by the results we are announcing today,”
John C. Lechleiter, Lilly’s chairman, said in a statement. “However,
Lilly’s innovation strategy, based on advancing a pipeline of nearly
70 molecules currently in clinical development, does not rest on the
success or failure of any single compound.”
Lilly’s failure in the final phase of an Alzheimer’s trial follows
misses by Myriad Genetics and by the team of Pfizer and Medivation.
Another closely watched drug being developed by Pfizer, Johnson &
Johnson and Elan has had mixed results in a middle-stage clinical
trial. Several prescription drugs are approved to treat symptoms of
Alzheimer’s, but none stop its progression.
Lilly’s drug was intended to reduce production of so-called amyloid
beta plaques in the brain by inhibiting the activity of an enzyme
called gamma secretase.
Dr. Siemers of Lilly said the failed trials might indicate that too
much reduction in amyloid beta unexpectedly harms cognitive functions,
or it may be that the problems arose from the drug’s effect on some 20
other proteins.
“It’s certainly a setback, but no one’s developed a treatment to slow
the rate of progression of the disease,” Dr. Siemers said. “This was I
think a very good shot on goal, but not Lilly’s only potential
treatment.”
Lilly is also testing an intravenous monoclonal antibody that reduces
amyloid beta, the plaque, by a different and more focused mechanism in
late-stage clinical trials. “They’re actually going quite well,” Dr.
Siemers said of those trials.
Alzheimer’s affects an estimated 5.3 million Americans. Dr. Steven T.
DeKosky, an Alzheimer’s researcher and dean of the University of
Virginia’s School of Medicine, said Lilly’s failure may show that
plaque reduction does not help patients with full-blown symptoms but
it could still help to prevent the disease.
“It’s too soon to say,” said Dr. DeKosky, who has consulted for Lilly
and other companies. “Having the drug fail doesn’t say the hypothesis
is wrong that amyloid causes the disease.” Some researchers are less
certain about the role that plaque may play in the onset of the
disease.
Ending the trial was not the only disappointing news Lilly received on
Tuesday. The Food and Drug Administration released a critical staff
review of the company’s application to market its blockbuster
antidepressant Cymbalta for the treatment of chronic pain.
The review, to be considered by an F.D.A. advisory committee on
Thursday, questioned Lilly’s statistical methods and the risks of
liver toxicity. Cymbalta, Lilly’s second-best-selling drug behind
Zyprexa, is approved for major depression, anxiety, diabetic pain and
fibromyalgia, but Lilly is seeking a vast new market in chronic pain.
Seamus Fernandez, a Leerink Swann analyst, said in an investor note
that the F.D.A. staff report still showed a likelihood of expanding
the Cymbalta label to include chronic pain. As for the Alzheimer’s
setback, he said by e-mail, “It was a big upside opportunity — very
high risk, high reward — this was basically Lilly swinging for the
fences.”
Last Thursday, the company lost a court ruling on patent protection
for its attention-deficit drug Strattera. Last month, it lost an
appellate court decision on a patent for the cancer drug Gemzar. And
in the last year, sales have been disappointing for the blood thinner
Effient, Lilly’s first new product in five years.
Mark Taylor, a spokesman, said Lilly was still optimistic about
Effient. But another competitor looms in the $6 billion anticoagulant
market: Brilinta from AstraZeneca is expected to be approved by the
F.D.A. by Sept. 16.
Lilly is already facing the biggest “patent cliff” in the industry.
Five of its six leading products face generic competition in the next
four years. Barbara Ryan, a stock analyst with Deutsche Bank, said
Lilly’s earnings will decline 35 percent by 2014 unless it makes one
of the larger acquisitions it has historically resisted.
“Each individual issue is not necessarily all that significant, but
collectively Lilly faces a real uphill battle because they face a
significant amount of generic competition over the next several years
and they are making a singular bet on their pipeline,” Ms. Ryan said
in an interview. “And the news hasn’t been very good.”
Andrew Pollack contributed reporting.
KMDickson