Eli Lilly and Company

     
BW20021101002143  20021101T134705Z UTC


( BW)(ELI-LILLY-&-CO)(BC43) Eli Lilly and Company: Once-Daily
Administration of Atomoxetine Reduced ADHD Symptoms Into The Evening

    Business Editors
    UK REGULATORY NEWS

    INDIANAPOLIS--(BUSINESS WIRE)--Nov. 1, 2002--    

A once-daily dose of atomoxetine, an investigational compound,
significantly reduced core symptoms of Attention-Deficit/Hyperactivity
Disorder (ADHD) in children and adolescents, according to a paper
published in the November issue of the American Journal of Psychiatry
(Volume 159, Number 11).

Symptom reduction lasted into the evening without causing insomnia.
Other studies have shown no significant differences in insomnia
between atomoxetine and placebo. Atomoxetine is a selective
norepinephrine reuptake inhibitor.

The 6-week, randomized, placebo-controlled study of 171 patients found
atomoxetine significantly reduced overall ADHD symptoms as well as
inattentive and hyperactive/impulsive symptoms, as assessed by
parents, teachers and clinical investigators. This was the first
atomoxetine study to provide evidence of effect based on teacher
ratings.

In addition, parent ratings, using a diary scale developed by Lilly,
suggested atomoxetine continued to work late in the day, significantly
reducing inattention during late afternoon/early evening, and reducing
difficulties settling at bedtime.

"Effective treatment of ADHD involves not only a reduction of ADHD
symptoms, but also an improvement in social and family function," said
study co-author Jeffrey Newcorn, M.D., Associate Professor of
Psychiatry and Pediatrics, Mount Sinai School of Medicine, and
Director, Division of Child and Adolescent Psychiatry, Mount Sinai
Medical Center. "A treatment that provides symptom control into the
evening has the potential to significantly improve family
interactions."

Study Design

The study included 171 children and adolescents, ages 6-16, who met
criteria for ADHD as spelled out in the Diagnostic and Statistical
Manual for Mental Disorders, 4th edition (DSM-IV). The DSM-IV includes
18 core symptoms of ADHD - nine related to inattention and nine
related to hyperactivity and impulsivity. All diagnoses were confirmed
through clinical interviews.

Exclusion criteria included serious medical illness, a history of
psychosis or bipolar disorder, alcohol or drug abuse within the past 3
months, and ongoing use of psychoactive medications other than the
study drug.

After an evaluation and drug washout period, patients were randomized
to either atomoxetine or placebo under double-blind conditions for 6
weeks, with weekly visits. Atomoxetine dosages were based on weight,
with an average final dose of 1.3 milligrams per kilogram per day.

The primary measure of symptom response was assessed using the ADHD
Rating Scale-IV-Parent Version: Investigator Administered (ADHD RS),
an 18-item scale based on an interview with the patient's primary
caretaker. Each item on the ADHD RS corresponds to one of the 18
DSM-IV criteria. In addition, a 13-item parent-rated diary was
developed by Lilly to assess efficacy during evening and early morning
periods. Symptoms assessed included evening and early morning
inattentiveness/distractibility, ability to concentrate on structured
tasks, hyperactivity/impulsivity and oppositionality. The study also
used the Conners' Parent and Conners' Teacher Rating Scales.

Results

ADHD-RS total score fell by an average of 12.8 points for patients
randomized to atomoxetine, compared with 5.0 points for patients on
placebo. Improvements were measurable for patients randomized to
atomoxetine beginning at 1 week and at all subsequent visits.
Superiority to placebo was also demonstrated on the ADHD Index scores
of the Conners' Parent Rating Scale (7.6, atomoxetine; 2.4, placebo)
and the Conners' Teacher Rating Scale (5.1, atomoxetine; 1.6,
placebo).

"The most striking finding of this study is the suggestion that one
dose of atomoxetine in the morning produced symptom improvements that
persisted into the evening, despite the short plasma half-life of the
medication, and without causing insomnia," said lead author David
Michelson, M.D., medical director, Eli Lilly and Company.

Atomoxetine showed greater improvement than placebo on two items
tracked in the parent diaries: inattention during late afternoon and
early evening, and difficulty settling at bedtime. The average scores
for "inattentive and distractable during the evening" fell 36.8
percent for patients on atomoxetine, from 1.9 to 1.2. That compares
with a reduction from 1.8 to 1.5, or 16.7 percent, for patients on
placebo. The average scores for difficulty settling at bedtime fell
from 1.8 to 1.1, or 38.9 percent, for patients on atomoxetine,
compared with a reduction from 1.7 to 1.4, or 17.6 percent, for those
on placebo. Other aspects of behavior were tracked in the parental
diaries, but changes observed were not statistically significant.

Limitations

Interpretation of the results is limited by several factors. This
study did not include a twice-daily dosing arm, therefore no direct
comparison of the relative efficacy of once- versus twice-daily
atomoxetine administration can be definitively determined. Also, the
dose range used in this study was based on the results of a
dose-response study that employed twice-daily dosing, and it is
possible that a different range would be optimal for once-daily
dosing.

Safety Information

In the study,the overall safety and tolerability of atomoxetine was
good. There were no statistically significant differences in the
number of discontinuations between atomoxetine and placebo. Only two
patients receiving atomoxetine discontinued because of adverse events
(2 percent) compared to one patient in the placebo group (1 percent).
The most common side effects for atomoxetine (greater than 16 percent)
were headache, rhinitis, abdominal pain and decreased appetite.

Atomoxetine

Atomoxetine is a selective norepinephrine reuptake inhibitor being
developed by Eli Lilly and Company (NYSE:LLY) as a treatment for ADHD
in children, adolescents and adults. Scientists believe it works by
selectively blocking the reabsorption of norepinephrine into certain
nerve cells in the brain. Norepinephrine is a neurotransmitter, a
chemical that moves messages from brain cell to brain cell, and is
thought to be important in regulating attention and controlling
impulses. While significant symptom reduction was observed at one week
in this study, data presented at a recent scientific meeting may
suggest symptom improvement as early as one day.(1)

Lilly received an approvable letter from the U.S. Food and Drug
Administration (FDA) for Strattera(TM) (atomoxetine hydrochloride) in
August 2002. If approved by regulators, atomoxetine will be the first
new class of medication for ADHD in decades. It also will be the only
medication indicated for the treatment of ADHD that is not a
stimulant.

ADHD affects 3-7 percent of school age children(2) and manifests
itself in levels of attention, concentration, activity,
distractibility, and impulsivity that are inappropriate to the child's
age.(3) Experts estimate 60 percent of children with the disorder
carry their symptoms into adulthood.(4)

Lilly, 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 organizations. Headquartered in
Indianapolis, Ind., Lilly provides answers - through medicines and
information - for some of the world's most urgent medical needs.

This news release contains forward-looking statements that reflect
management's current beliefs about the potential for atomoxetine in
the treatment of attention deficit hyperactivity disorder (ADHD) in
children. However, as with any pharmaceutical under development, there
are significant risks and uncertainties in the process of development
and regulatory review. There are no guarantees that the product will
receive regulatory approvals or prove to be commercially successful.
There is also no assurance of the timing of final FDA action on the
compound. For additional information about the factors that affect the
company's business, please see Exhibit 99 to the company's latest Form
10-Q. The company undertakes no duty to update forward-looking
statements.

(1) Data on file. Eli Lilly and Company.

(2) American Psychiatric Association: Diagnostic and Statistical
Manual of Mental Disorders, fourth edition, text revision. Washington,
DC, American Psychiatric Association, 2000.

(3) American Psychiatric Association: Diagnostic and Statistical
Manual of Mental Disorders, fourth edition. Washington, DC, American
Psychiatric Association, 1994.

(4) American Psychiatric Association: DSM-IV-TR.2000.85-93 Schweitzer
JB, et al. Attention-deficit/hyperactivity disorder. Med Clin of North
Am. 2001; 85(3):757-777

   Short Name: (Eli) & Co
   Category Code: MSC
   Sequence Number: 00001123
   Time of Receipt (offset from UTC): 20021101T123159+0000

    --30--djl/cl* mh/uk

    CONTACT: Eli Lilly and Company, Indianapolis
             David Shaffer, 317/651-3710

    KEYWORD: INDIANA UNITED KINGDOM INTERNATIONAL EUROPE
    INDUSTRY KEYWORD: MEDICAL BIOTECHNOLOGY PHARMACEUTICAL PRODUCT
    SOURCE: Lilly (Eli) & Co

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