Patients Taking Cymbalta(R) Experienced Reduced Chronic Low Back Pain in New Study

INDIANAPOLIS, Aug. 25 — Data from a new study suggest
that Cymbalta (duloxetine HCl) 60-120 mg once daily significantly reduced
chronic low back pain, as measured by the Brief Pain Inventory (BPI)
24-hour average pain score, compared with placebo.(1) Results from the
double-blind, 13-week, placebo-controlled study of 236 patients were
presented today at the annual congress of the European Federation of
Neurological Societies (EFNS) in Madrid, Spain.

Duloxetine-treated patients reported significantly greater reduction in
pain scores than placebo-treated patients. Thirty-one percent of
duloxetine-treated patients experienced a 50 percent reduction in pain,
compared with 19 percent of placebo-treated patients, as measured by an
11-point Likert pain scale. Physicians consider a pain reduction of at
least 30 percent as clinically significant.(2)

Treatment with duloxetine also was associated with improved patient
outcomes as measured by the Patient Global Impressions of Improvement
(PGI-I), and physical functioning as measured by the Roland Morris
Disability Questionnaire (RMDQ-24).

Significantly more patients in the duloxetine group discontinued
because of adverse events. In this study, the most common adverse events
(those occurring in more than 5 percent of patients in the duloxetine
group) were nausea, dry mouth, fatigue, diarrhea, excessive sweating
(hyperhidrosis), dizziness and constipation. Adverse events were similar to
those seen in previous duloxetine studies in other disease states.

“Chronic low back pain can have a significant impact on a person’s
ability to do the things they enjoy,” said Vladimir Skljarevski, lead study
author and a neurologist and medical fellow at Lilly Research Laboratories.
“This research may offer hope to those dealing with this debilitating
condition.”

Additional Study Highlights
– The repeated measures analysis using the patient diary demonstrated a
significantly greater reduction in pain in the first week after
starting the 60 mg daily dose, which continued throughout the 13 weeks
of the acute therapy phase.
– Superiority to placebo in most secondary analyses including eight out
of the remaining 10 BPI items (e.g., weekly 24-hour average pain score,
weekly 24-hour worst pain and weekly 24-hour night pain) was observed.
– Superiority to placebo was not observed in two BPI items: pain
interference with general activity and pain interference with sleep.
– Statistically significant differences in three individual items in the
Short Form-36 of the Medical Outcomes Study (SF-36) – bodily pain,
general health and vitality – were observed.
– Statistically significant differences were not observed in the
remaining items in the Short Form-36 of the Medical Outcomes Study,
including mental component summary, physical component summary,
mental health, physical functioning, role-emotion, role-physical and
social functioning.
– The duloxetine treatment group experienced a significantly greater
improvement on the work-activity impairment score compared with the
placebo treatment group as measured by the Work Productivity and
Impairment Scale (WPAI).

Study Methods

Adult patients given duloxetine (n=115) and those given placebo (n=121)
with a history of non-neuropathic chronic low back pain for more than six
months with a weekly mean 24-hour average pain score greater than or equal
to 4 at baseline (0-10 scale) and without major depressive disorder were
initially treated with duloxetine 60 mg once daily for the first seven
weeks in this randomized placebo-controlled trial. After seven weeks of
duloxetine treatment, patients reporting less than 30 percent pain
reduction (non-responders) had their dose increased to 120 mg once daily.
Responders continued on 60 mg once daily. The study’s primary objective was
the reduction of the BPI 24-hour average pain score. Secondary measures
included RMDQ-24, PGI-I, BPI Severity portion (BPI-S) and BPI Interference
portion (BPI-I), diary-based weekly mean of the 24-hour average pain score,
Clinical Global Impression of Severity (CGI-S), and response rates. Health
outcomes, safety and tolerability also were assessed. Continuous efficacy
variables were analyzed using analysis-of-variance (ANOVA) with treatment
and investigator in the model, or analysis of covariance, with baseline,
treatment and investigator in the model, and the stratifying variable of
NSAID use (Yes/No). Mixed-model repeated measures (MMRM) analysis also was
used to measure improvement at all time points. Treatment groups were
compared based on the difference between least-squares means using
two-sided testing at the 0.05 significance level. Safety analyses were
conducted to compare treatment groups using Fisher’s exact test.

Duloxetine data also presented at 12th World Congress of Pain

Data from a separate duloxetine chronic low back pain study were
presented on Aug. 21 at the 12th World Congress of Pain in Glasgow,
Scotland. At study endpoint, duloxetine did not significantly differ from
placebo on the primary measure of weekly mean 24-hour average pain
score.(3) However, patients taking duloxetine 60 mg once daily showed
significant pain reductions compared with placebo from week three through
week 11 of the 13-week trial.(3) This was the first study designed to
assess the effect of duloxetine on the reduction of chronic low back pain
compared with placebo.

In the 13-week, double-blind, randomized, placebo-controlled study
(n=404), patients taking duloxetine 60 mg once daily experienced
statistically significant improvements in several secondary outcome
measures compared with placebo. Patients taking duloxetine 60 mg once daily
also experienced a statistically significant improvement in patient
outcomes as measured by the PGI-I and physical functioning as measured by
the RMDQ-24.(3) In this study, the most common adverse events (those
occurring in more than 5 percent of patients in the duloxetine group) were
nausea, insomnia, dry mouth, constipation, headache, diarrhea, dizziness,
somnolence (drowsiness) and fatigue.

It is estimated that at least 15 million adults in the United States
have chronic low back pain.(4) According to the International Association
for the Study of Pain (IASP), pain is an unpleasant sensory and emotional
experience associated with actual or potential tissue damage, or described
in terms of such damage.(5) Chronic pain is defined as pain that persists
beyond acute pain or beyond the expected time for an injury to heal.(6) Men
and women are equally affected by chronic low back pain, and it occurs most
often between ages 30 and 50.(7)

About Cymbalta

Serotonin and norepinephrine in the brain and spinal cord are believed
to both mediate core mood symptoms and help regulate the perception of
pain. Based on preclinical studies, Cymbalta is a balanced and potent
reuptake inhibitor of serotonin and norepinephrine that is believed to
potentiate the activity of these chemicals in the central nervous system
(brain and spinal cord). While the mechanism of action of Cymbalta is not
fully known, scientists believe its effects on depression and anxiety
symptoms, as well as its effect on pain perception, may be due to
increasing the activity of serotonin and norepinephrine in the central
nervous system.

Cymbalta is approved in the United States for the acute and maintenance
treatment of major depressive disorder, the acute treatment of generalized
anxiety disorder, and the management of fibromyalgia and diabetic
peripheral neuropathic pain in adults age 18 years and older. Cymbalta is
not approved for use in pediatric patients.

Important Safety Information

Cymbalta is approved to treat major depressive disorder and generalized
anxiety disorder, and to manage diabetic peripheral neuropathic pain and
fibromyalgia. Antidepressants can increase suicidal thoughts and behaviors
in children, adolescents, and young adults. Patients should call their
doctor right away if they experience new or worsening depression symptoms,
unusual changes in behavior, or thoughts of suicide. Be especially
observant within the first few months of treatment or after a change in
dose. Cymbalta is approved only for adults 18 and over.

Cymbalta is not for everyone. Patients should not take Cymbalta if they
have recently taken a type of antidepressant called a monoamine oxidase
inhibitor (MAOI), are taking Mellaril(R) (thioridazine), or have
uncontrolled glaucoma. Patients should speak with their doctor about any
medical conditions they may have including kidney problems, glaucoma, or
diabetes. Patients should talk to their doctor if they have itching, right
upper belly pain, dark urine, yellow skin or eyes, or unexplained flu-like
symptoms, which may be signs of liver problems. Severe liver problems,
sometimes fatal, have been reported. They should also talk to their doctor
about alcohol consumption. Patients should tell their doctor about all
their medicines, including those for migraine, to avoid a potentially
life-threatening condition. Taking Cymbalta with NSAID pain relievers,
aspirin, or blood thinners may increase bleeding risk. Patients should
consult with their doctor before stopping Cymbalta or changing the dose and
if they are pregnant or nursing.

Patients taking Cymbalta may experience dizziness or fainting upon
standing. The most common side effects of Cymbalta include nausea, dry
mouth, sleepiness, and constipation. This is not a complete list of side
effects.

For full Patient Information, visit http://www.cymbalta.com.

For full Prescribing Information, including Boxed Warning and
medication guide, visit http://www.cymbalta.com.

About Eli Lilly and Company

Lilly, a leading innovation-driven corporation, is developing a growing
portfolio of first-in-class and 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.
Additional information about Lilly is available at http://www.lilly.com.

P-LLY

This press release contains forward-looking statements about the
potential of Cymbalta for chronic pain including the management of chronic
low back pain and reflects Lilly’s current beliefs. However, as with any
pharmaceutical product, there are substantial risks and uncertainties in
the process of development and commercialization. There is no guarantee
that the product will continue to be commercially successful. For further
discussion of these and other risks and uncertainties, see Lilly’s filings
with the United States Securities and Exchange Commission. Lilly undertakes
no duty to update forward-looking statements.

(1) Skljarevski, V. et al. Efficacy of Duloxetine in Chronic Low Back
Pain. Poster presented at the European Federation of Neurological Societies
Annual Congress. 25 August 2008.

(2) Farrar JT, JP Young Jr., L LaMoreaux, JL Werth, RM Poole. Clinical
importance of changes in chronic pain intensity measured on an 11-point
numerical pain rating scale. 2001. Pain (94):149-158.

(3) Skljarevski, V. et al. Duloxetine versus Placebo in the Treatment
of Chronic Low Back Pain. Poster presented at the 12th World Congress of
Pain. 21 August 2008.

(4) Praemer A, Furnes S, Rice DP. Musculoskeletal conditions in the
United States. Rosemont: AAUS, 1992: 1-99.

(5) International Association for the Study of Pain. “IASP Pain
Terminology” Available at: http://www.iasp-
pain.org/AM/Template.cfm?Section=General_Resource_Links&Template=/CM/HTMLDi
spl ay.cfm&ContentID=3058#Pain. Accessed on 5/27/08.

(6) American Pain Society. “Pain Control in the Primary Care Setting.”
2006:15.

(7) National Institute of Neurological Disorders and Stroke. “Low Back
Pain Fact Sheet.” Available at:
http://www.ninds.nih.gov/disorders/backpain/detail_backpain.htm. Accessed
on June 25, 2008.

SOURCE Eli Lilly and Company