Lilly Presents Follow-Up Data on Semagacestat to Assist Future Alzheimer’s Disease Research

INDIANAPOLIS, July 19, 2011 /PRNewswire/ — Data were presented today from the
first of two Phase III trials of semagacestat, including data from a 32 week
follow-up period after dosing was halted in August 2010. Semagacestat is a gamma
secretase inhibitor that had been studied as a potential treatment for
Alzheimer’s disease. Results shown today provided patient outcomes from the
active treatment portion of the study and from a modified portion of the study
conducted after dosing with semagacestat was stopped. Lilly presented the data
during a plenary session at the Alzheimer’s Association International Conference
2011 (AAIC 2011) in Paris, France.

The dosing in both semagacestat trials was halted in August 2010 because
preliminary results from the two Phase III trials showed semagacestat did not
slow Alzheimer’s disease progression and was associated with worsening of
clinical measures of cognition and the ability to perform activities of daily
living. Lilly continued to gather data, including cognitive scores, for 32 weeks
after dosing was stopped.

“When we made the decision to halt dosing in the trials, we committed to
collecting this data in an effort to benefit future Alzheimer’s research and to
provide safety follow-up for the patients,” said Eric Siemers, M.D., senior
medical director for the Alzheimer’s Disease Team at Eli Lilly and Company. “We
have a great deal of appreciation and respect for the dedication of the patients
and caregivers who remained committed to the semagacestat trials from the
beginning until these follow-up data were collected. By obtaining this
information, future research efforts can be guided much more effectively.”

The study data confirmed preliminary results that showed that during the period
of dosing, patients receiving semagacestat declined at a greater rate than
patients taking placebo. During the follow-up period after dosing was halted,
the cognitive and functional deficits of the patients initially treated with
semagacestat remained worse than the deficits of patients initially treated with
placebo. However, the course of the decline over time in the two groups did not
diverge further after dosing was stopped.

Alzheimer’s disease is a fatal form of dementia that causes progressive decline
in memory and other aspects of cognition.(1) Researchers do not know exactly
what causes Alzheimer’s, but one hypothesis is that beta-amyloid protein plays
an important role.(1,2)

“Although today we focused on what happened with semagacestat, the broader
important point is that Lilly remains committed to Alzheimer’s research and the
Alzheimer’s disease community,” said Dr. Siemers. “We continue to move forward
with the development of other molecules in our pipeline aimed at slowing the
progression of Alzheimer’s disease.”

Study Methods

An external Data Monitoring Committee (DMC) was established prior to beginning
the semagacestat IDENTITY studies so that they could monitor safety during the
trials; unlike the patients and investigators, the DMC knew which patients were
taking semagacestat and which patients were taking placebo. A planned analysis
of the cognitive data by the DMC partway through the trial showed the increased
rate of worsening, leading to the decision to discontinue dosing of
semagacestat. The IDENTITY trials were then modified substantially in order to
obtain more data for approximately seven months while the patients were no
longer taking semagacestat. By studying the patients after stopping dosing, some
of the factors that may have led to the increased cognitive decline could be
more fully understood.

Study Findings

After 76 weeks of treatment with semagacestat or placebo, patients taking
placebo (501 patients) worsened by 6.19 points on the Alzheimer’s Disease
Assessment Scale-cognitive subscale (ADAS-cog11), which is approximately the
amount of change expected for placebo-treated patients over this time period.
Patients taking 100 mg semagacestat daily (506 patients) worsened by 7.29
points; patients taking 140 mg semagacestat (527 patients) worsened by 7.68
points. Over the seven months after stopping dosing of semagacestat, the
differences between placebo- and semagacestat-treated patients were largely
unchanged. The adverse effects seen in the IDENTITY trial were similar to those
seen during Phase II studies. As disclosed previously and communicated to
investigators, patients and regulators earlier in the trials, an increased rate
of skin cancer was seen in patients taking semagacestat; this adverse effect was
not seen in Phase II studies. The adverse events and laboratory abnormalities
seen in the semagacestat-treated subjects resolved shortly after stopping
dosing.

About Semagacestat

Semagacestat was an oral agent designed to reduce the body’s production of
beta-amyloid, 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 beta-amyloid.

About Eli Lilly and Company

Lilly, a leading innovation-driven corporation, is developing a growing
portfolio of pharmaceutical products by applying the latest research from its
own worldwide laboratories and from collaborations with eminent scientific
organizations. Headquartered in Indianapolis, Ind., Lilly provides answers -
through medicines and information – for some of the world’s most urgent medical
needs. Additional information about Lilly is available at www.lilly.com.

This press release contains forward-looking statements about compounds currently
in clinical development for Alzheimer’s disease. It reflects Lilly’s current
beliefs; however, as with any such undertaking, there are substantial risks and
uncertainties in the process of drug development and commercialization. There is
no guarantee that any of these compounds will be approved by the relevant
regulatory authorities or be commercially successful. For further discussion of
these and other risks and uncertainties, please see Lilly’s latest Forms 10-Q
and 10-K filed with the U.S. Securities and Exchange Commission. Lilly
undertakes no duty to update forward-looking statements.

P-LLY

(1)”Dementia: Hope Through Research.” National Institute of Neurological
Disorders and Stroke, National Institutes of Health. Available at:
http://www.ninds.nih.gov/disorders/dementias/detail_dementia.htm. Accessed on
June 28, 2011.

(2)Hardy, John & Selkoe, Dennis. “The Amyloid Hypothesis of Alzheimer’s Disease:
Progress and Problems on the Road to Therapeutics.” Science 2002 (297); 353-356.

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SOURCE Eli Lilly and Company