Alzheimer's, Dementia & Mental Health
Battle Against Alzheimer’s Disease Hits Wall as Drug
Test Stopped; Maybe Plaque Not Cause
Eli Lilly’s semagacestat targeted amyloid beta
plaques but patients got worse
Aug. 19, 2010 – The efforts to prevent or
successfully treat Alzheimer’s disease – the disease most feared by
senior citizens - with drugs has never advanced very far, but these
efforts suffered a major setback this week when Eli Lilly and Company
announced it was halting development of semagacestat. This potential
treatment for AD was in advanced clinical trials when it was discovered
to be making patients worse instead of better. Many see this failure as
a major blow to the most popular theory on the cause of the disease.
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Alzheimer's, Dementia & Mental Health |
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The Lilly announcement said, “Studies showed it did
not slow disease progression and was associated with worsening of
clinical measures of cognition and the ability to perform activities of
daily living.”
"This is disappointing news for the millions of
Alzheimer's patients and their families worldwide who anxiously await a
successful treatment for this devastating illness," said Jan M.
Lundberg, Ph.D., Executive Vice President, Science and Technology, and
President, Lilly Research Laboratories. "This is a setback, but Lilly's
commitment to beating Alzheimer's will not waver."
Lilly is instructing clinical trial investigators
for all semagacestat studies to contact study participants as soon as
possible and tell them to immediately stop taking the study drug. Study
participants or caregivers should call their study physician to schedule
their next appointment. Lilly has also informed regulatory agencies and
is providing instructions to investigators outlining the process for
finalizing the studies.
In two pivotal Phase III trials, semagacestat was
compared with placebo in more than 2,600 patients with mild-to-moderate
Alzheimer's disease.
Semagacestat was designed to reduce the body's
production of amyloid beta plaques, which scientists believe play an
important role in causing Alzheimer's disease. Semagacestat is believed
to block the activity of gamma secretase, an enzyme that is essential to
the body's production of amyloid beta plaques, according to the company.
It was being tested in two Phase III clinical trials called IDENTITY and
IDENTITY-2.
Lilly’s interim analysis showed that, as expected,
cognition and the ability to complete activities of daily living of
placebo-treated patients worsened. However, by these same measures,
patients treated with semagacestat worsened to a statistically
significantly greater degree than those treated with placebo.
In
addition, data showed semagacestat is associated with an increased risk
of skin cancer compared with those who received placebo.
Semagacestat was one of many drugs being tested
that focus on amyloid-beta proteins, which are believed to play a
critical role in Alzheimer's disease. Lilly actually has another
amyloid-beta compound, solanezumab, in Phase III trials and says this
testing will continue.
The company says these two compounds have
“different mechanisms of action.” Lilly also has two other compounds in
earlier stages of clinical development that will also continue.
Lilly's clinical team will continue to gather and
evaluate data from these studies, and will publish the results for the
benefit of future Alzheimer's research.
Although dosing with semagacestat is being stopped, Lilly plans to continue collecting safety
data, including cognitive scores, for at least six months through
regularly scheduled follow-up visits with study physicians and
modifications of the existing Phase III protocols.
These additional follow-up visits are expected to
help answer a number of important questions, including whether the
differences between patients who received semagacestat and those who
received placebo will continue after semagacestat has been discontinued.
Other smaller short-term studies will be stopped and participants will
receive appropriate follow-up.
"We are clearly disappointed by the results," said
John C. Lechleiter Ph.D., Lilly's chairman and chief executive officer.
He said, however, that the company has nearly 70 molecules currently in
clinical development.
"Pharmaceutical research always carries risk, as
these results show. But it offers as well the potential for tremendous
reward for millions of patients who await new medicines. Despite this
and other recent setbacks, Eli Lilly and Company remains financially
strong and is even more determined to prevail in our quest to provide
new treatments for Alzheimer's and other serious diseases," added
Lechleiter.
About Alzheimer's disease
Alzheimer's disease is a fatal form of dementia
that causes progressive decline in memory and other aspects of
cognition. It occurs when billions of neurons in the brain begin dying
prematurely. Researchers don't know exactly what causes it, but the
leading hypothesis is that amyloid beta plaques play an important role.
About the IDENTITY trials
IDENTITY (Interrupting Alzheimer's Dementia by
EvaluatiNg Treatment of AmyloId PaThologY) and IDENTITY-2 are Lilly's
Phase III placebo-controlled trials studying semagacestat, a gamma-secretase
inhibitor being investigated as a potential treatment to slow the
progression of mild to moderate Alzheimer's disease. Both Phase III
trials are fully enrolled, with more than 2,600 patients from 31
countries, and include a treatment period of approximately 21 months. An
open-label extension study (IDENTITY-XT) is available to all
participants completing either study.
All study participants had to be at least 55 years
old and meet the National Institute of Neurological and Communicative
Disorders and Stroke/Alzheimer's Disease and Related Disorders
Association (NINCDS/ADRDA) criteria for probable Alzheimer's disease,
with certain assessment scores indicating mild to moderate Alzheimer's
disease. Patients with more advanced Alzheimer's disease were not
included in the studies.
>> Eli Lilly and Company (NYSE:LLY)
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