Two New Head-to-Head Studies Assess Patient Preference Between Lilly ICOS' Cialis -tadalafil- and Viagra -sildenafil citrate- fo

    Lilly
Jane Calloway, 317-651-5870
    or
ICOS
Lacy Fitzpatrick, 425-415-2207

Lilly ICOS LLC (NYSE:LLY)(Nasdaq:ICOS). In a recently published study,
90 percent of men with erectile dysfunction (ED) who had previously
used Viagra(R) (sildenafil citrate)(1), preferred to continue
treatment with Cialis(R) (tadalafil) after treatment with Viagra
followed by Cialis 20mg. Another study showed 66 percent of men
starting treatment for ED (most with no prior exposure to Viagra)
favored Cialis 20mg over Viagra 50mg after four-week treatment
intervals with each drug. These two separate studies are published in
the November 2003 issue of Clinical Therapeutics(2). Both studies were
designed and sponsored by Lilly ICOS LLC, which is marketing Cialis
for the treatment of ED.(3)

"As a choice of effective and well tolerated oral ED medications
becomes available to patients, physicians will actually use patient
trial and preference in their clinical practice to determine which
treatments to prescribe," said Fred Govier, M.D., Professor of
Urology, University of Washington, Seattle, and lead investigator of
one of the studies. "Patient preference has become an interesting
topic of study as treatment options allow doctors to select the
medication that best suits the unique needs of each patient and his
partner."

Switching from Viagra to Cialis in Patients with Erectile Dysfunction
-- Methodology and Key Findings

The first trial was an open-label study that enrolled men who were
already undergoing ED treatment with Viagra at stable doses of up to
100mg for at least six weeks. Patients remained on their dose of
Viagra for three weeks after enrolling in the trial and then were
switched to treatment with Cialis 20mg for nine weeks after a
seven-day washout period(4). They were then given the opportunity to
choose their preferred treatment for a six-month extension phase
during which they would receive their ED medication of choice free of
charge. At this point of the study, 90.5 percent of men chose to
receive Cialis, while 9.5 percent opted to receive Viagra (p less than
0.001). The results did not vary significantly between sub-groupings
based on age, etiology, duration or severity of ED or presence of
common co-morbid conditions. Also, results did not vary based upon
Viagra dose at entry, with 90 percent of men on Viagra 50mg and 89
percent of men on Viagra 100mg preferring to switch to Cialis.

All men in this multi-country study were treated with Viagra at their
previously prescribed stable dose for three weeks after entry into the
study and were given dosing instructions consistent with its
labelling, noting that Viagra may be effective up to four hours after
dosing and that a high fat meal may delay the onset of effect(5).
After a one-week washout period, the men were switched to treatment
with Cialis 20mg for nine weeks. Every three weeks, the men were
provided dosing instructions which indicated the following: Cialis
could be effective for up to 24 hours; the duration of effectiveness
could allow for flexibility and spontaneity in their sex lives; Cialis
could be taken with or without food. Upon conclusion of the Cialis
treatment, all men completing the study (n=147) were asked to specify
which product they would like to receive during a six-month extension
phase, in which patients received their treatment of choice free of
charge.

While the methodology of the study was designed to mimic everyday
clinical practice in many ways, the authors acknowledged that certain
aspects of the study design may have had some influence over the
outcome, and may limit the ability to generalize the results. Dosing
instructions for Viagra were derived from the US and EU package
inserts, but Cialis had not yet been approved at the time the study
took place. Therefore, dosing instructions for Cialis were derived
from previous clinical trial experience. Patients were made aware of
the flexibility and spontaneity that could result from Cialis' 24-hour
duration of effectiveness, and this may have introduced some bias. In
addition, dosing instructions were given at three-week intervals, so
men on Cialis received these instructions three times during the
Cialis treatment period. Dosing instructions were repeated to overcome
the mindset that an ED drug must be taken shortly before anticipated
sexual intercourse. It was thought that this mindset might be
particularly prevalent in men who had been taking Viagra. The sequence
of treatment was such that patients were asked to choose a preferred
treatment shortly after completing treatment with Cialis. Finally,
Cialis 20mg was used because it was the anticipated starting dose at
the time the study began(6). Cialis 20mg is the recommended starting
dose in almost half of the countries where it is approved, including
Canada, Mexico, and Brazil. The recommended starting dose in Europe is
Cialis 10mg.

During the treatment phases of the study, side effects occurring in
greater than two percent of men taking both Cialis and Viagra were
headache (five percent each for Cialis and Viagra), nasal congestion
(four percent for Cialis and six percent for Viagra), upset stomach
(three percent for Cialis and one percent for Viagra), flushing (three
percent for Cialis and seven percent for Viagra) and nasopharyngitis,
similar to the common cold (one percent for Cialis and three percent
for Viagra). Most side effects were mild or moderate in intensity. Two
serious adverse events occurred during the Cialis initiation phase;
neither was considered to be related to the study drug. Three patients
discontinued use due to adverse events during the Cialis initiation
phase. There were no significant differences in the incidence of
treatment-emergent adverse events across ED therapies.

Patient Preference for Cialis Versus Viagra During ED Treatment
Initiation -- Methodology and Key Findings

The second study was a head-to-head, randomized double-blind,
cross-over study with the aim of evaluating patient preference for ED
treatment after initial four-week treatment periods with Cialis 20mg
and Viagra 50mg. In the study, 66 percent of men preferred Cialis
compared to 34 percent who chose Viagra (p less than 0.001).
Preference did not differ significantly between groups based on
treatment sequence, duration of ED, or presence of common co-morbid
conditions.

In this randomized, double-blind, fixed-dose study, 215 men with mild
to severe ED between the ages of 18 and 65, who had no experience with
Viagra (approximately 85 percent of patients) or very limited
experience with Viagra, were randomly divided into two groups and
began ED treatment with either Cialis 20mg or Viagra 50mg for four
weeks. Those patients randomized to Viagra received dosing instruction
consistent with Viagra labelling, and those patients randomized to
Cialis received Cialis dosing instructions (similar to those provided
in the study described above). Following a one-week washout period,
patients were changed to the other ED therapy, along with associated
dosing instructions, for four weeks. At the end of this second
treatment phase, all patients were assessed using the Treatment
Preference Question (TPQ): "Which treatment did you prefer?"

As with the study described above, authors recognized the study design
may limit the conclusions that can be drawn from the study. Cialis was
not yet approved when the study was conducted; therefore the dosing
instructions associated with Cialis were derived from clinical trial
experience, and references to spontaneity and flexibility that could
result from Cialis' duration of effectiveness in these instructions
may have introduced bias. This study compared the highest available
dose of Cialis, 20mg(7), with the 50mg recommended starting dose of
Viagra. The results may have been somewhat different if the highest
available dose of Viagra had been used(8).

In the study, side effects occurring in greater than two percent of
patients were headache (11 percent for Cialis and nine percent for
Viagra), upset stomach (six percent for Cialis and four percent for
Viagra), nasopharyngitis, similar to the common cold (five percent for
Cialis and three percent Viagra), flushing (three percent for Cialis
and five percent for Viagra), muscle ache (two percent for Cialis and
zero percent for Viagra); and nasal congestion (two percent for Cialis
and three percent for Viagra). Most side effects were mild or moderate
in intensity. Two patients discontinued treatment due to adverse
events (one on Cialis, and one on Viagra). One serious adverse event
occurred during the Viagra treatment that was considered to be not
related to the study drug. There were no significant differences in
the incidence of treatment emergent adverse events across these two
medications.

About ED

ED is defined as the consistent inability to attain and maintain an
erection sufficient for sexual intercourse. ED affects an estimated
152 million men and their partners worldwide(9). Up to 80 percent of
ED cases are caused by physiological conditions, including
cardiovascular disease and diabetes, with psychological factors
accounting for the remaining 20 percent. In many cases, however, both
psychological and physical factors contribute to the condition(10).

Cialis is available in more than 45 countries worldwide, including
Europe, Brazil, Mexico, Australia, New Zealand and Saudi Arabia.

About Lilly ICOS LLC

Lilly ICOS LLC, a joint venture between ICOS Corporation and Eli Lilly
and Company, developed tadalafil for the treatment of sexual
dysfunction.

Eli Lilly and Company, a leading innovation-driven corporation, is
developing a growing portfolio of best-in-class pharmaceutical
products by applying the latest research from its own worldwide
laboratories and from collaborations with eminent scientific
organisations. Headquartered in Indianapolis, Indiana, Lilly provides
answers - through medicines and information - for some of the world's
most urgent medical needs.

ICOS Corporation is a product-driven company that has expertise in
both protein-based and small molecule therapeutics. ICOS combines its
capabilities in molecular, cellular and structural biology,
high-throughput drug screening, medicinal chemistry and gene
expression profiling to develop highly innovative products expected to
have significant commercial potential. ICOS applies its integrated
approach to erectile dysfunction and other urologic disorders,
psoriasis, sepsis and inflammatory diseases. ICOS' strategy targets
multiple therapeutic areas with drugs that act through distinct
molecular mechanisms, increasing ICOS' opportunities to market
breakthrough products.

Certain of the matters discussed herein with respect to clinical
studies and ICOS and Lilly's products may constitute forward-looking
statements within the meaning of the Private Securities Litigation
Reform Act of 1995. Such forward-looking statements are based on
current expectations, estimates and projections about the industry,
management beliefs and certain assumptions made by the management.
Investors are cautioned that matters subject to forward-looking
statements involve risks and uncertainties, including economic,
competitive, governmental, technological and other factors discussed
in the two companies' respective filings with the Securities and
Exchange Commission, which may affect the business and prospects of
the two companies. More specifically, there can be no assurance that
this product will achieve commercial success or that competing
products will not pre-empt any market opportunity that might exist for
the product.

(1) Viagra(R) (sildenafil citrate) tablets, Pfizer Inc.

(2) Govier F, Potempa A-J, Kaufman J, Denne J, Kovalenko P, Ahuja S. A
double-blind, multicenter, crossover study to evaluate patient
preference for tadalafil 20 mg versus sildenafil 50 mg during
treatment initiation for erectile dysfunction. Clinical Therapeutics
2003; 25 (11): 2709-2723

(3) These studies were not designed to demonstrate nor to compare
efficacy of either product.

(4) The study was conducted at six sites in Sweden and Italy.

(5) Two-thirds of the patients took 50mg Viagra, 8 percent took 25mg,
1 percent took 75mg and 25 percent took 100mg. The starting dose of
Viagra is 50mg in most countries, with the option to increase or
reduce based on efficacy and tolerability.

(6) The number of patients on the highest approved dose of Viagra (100
mg) was capped at 35 percent, consistent with the proportion of
patients using this dose in Europe during the twelve-month period
prior to commencement of the study.

(7) Anticipated at the time to be the starting dose in most countries.

(8) These results are, however, consistent with some independent
crossover studies to be presented at the European Society of Sexual
Medicine meeting November 16-19, 2003.

(9) Aytac Ia, McKinlay JB, Krane RJ. The Likely Worldwide Increase in
Erectile Dysfunction Between 1995 and 2025 and Some Possible Policy
Consequences. BJU Int 1999; 84: 50-56

(10) Impotency Information from NIH. NIH Publication No. 95-3923.1995