Milnacipran Demonstrated Significant Improvement In Pain And The Core Symptoms Of Fibromyalgia Syndrome, Data Show

Total daily doses of milnacipran 100
and 200 mg Mg showed a statistically significant and clinically
Meaningful improvements in the two central pain and other symptoms
With fibromyalgia syndrome (FMS), based on the Phase III data
This week at the 2007 American College of Rheumatology meeting in Boston, MA
. The therapeutic effect of milnacipran among responders in a six-month study were
lasting up to a year in a double-blind study extension.

Although widespread chronic pain is the defining feature of the FMS,
you typically occurs, as part of a broader range of symptoms, including
fatigue, cognitive dysfunction, and reduced physical function . Milnacipran is the first
studied fibromyalgia treatment whose effectiveness has been rated
use of a composite approach requires responders,
One patient by patient basis over several simultaneous improvements FMS
domains. As such, composite responder analysis
represent a stricter assessment of the therapeutic effect as the evaluation of individual
symptoms.


order as a responder for the compound "pain of fibromyalgia"
endpoint, each patient had to demonstrate and simultaneously
clinically sensible improvements in two validated measures: pain and the overall impression of
disease. In addition to these criteria,
response of the composite "treatment of fibromyalgia syndrome"
endpoint also had to show improvement in a third validated measure:
The physical function. The results of two Phase III studies showed that
milnacipran demonstrated improvement in comparison with placebo in the treatment of both
the pain of fibromyalgia, and the broader syndrome of fibromyalgia.
In addition, data from a six-month extension study showed that the therapeutic effect of
milnacipran were lasting up to one year
therapy.


"Because patients with fibromyalgia experience a wide range of symptoms
The overlap with other conditions, diagnosis and treatment may
complicated. Currently, many physicians are with several
drugs to treat various symptoms of fibromyalgia, "said Daniel J. Clauw, MD, lead investigator
, chronic pain and fatigue Research Center, University of Michigan
. "There is a real unmet need for a therapy that will not only relieve pain
, but deals with the functional and physical aspects of the disease,
can have a significant impact on the patients quality of life."


, Study Methodology ,



In two double-blind, placebo-controlled, approval of the Phase III study
study (Study million-MD-02 and studying FMS - 031) with two parallel,
primary efficacy assessments consisted of compound responder analysis for the treatment of
Both fibromyalgia syndrome and the pain of fibromyalgia. Composite
pain response was defined as persons who have both an gr�ere or
amounting to 30% reduction in pain compared to baseline as measured by a visual analog scale
daily on an electronic patient record of experience diary
rated and who regard themselves as "very much improved" or "much improved" on
Patient Global Impression of Change (PGIC) scale. Fibromyalgia Syndrome
Composite response to meet the criteria and pain Composite
As proof of at least a 6-improving their SF-36 physical component summary
(SF-36 PCS) points.


Study million-MD-02, 1196 patients were randomized to receive either
milnacipran 100 mg / day (n = 399): 200 mg / day ( n = 396) or placebo (n = 401) on
a period of three months, 67.7% of which the process is completed.


study FMS - 031, 888 patients were randomized to receive either
milnacipran 100 mg / day (n = 224): 200 mg / day (n = 441 ) or placebo (n = 223)
six months, 63.6% of which were completed three months of treatment, and 57.6%
from which the full six months double-blind treatment. Were
results for all patients on the three and six months visited.


patients receiving the full six months of treatment in study
FMS - 031 were allowed to settle in a multicenter, dose-blinded, extension
study to evaluate the durability of response up to a year. Overall
Of 449 patients were either 200 mg / day (n = 209) or
Again randomized to 100 mg / day (n = 48) or 200 mg / day (n = 192) for an additional
six months. Evaluations of the effectiveness of change in pain, as measured using a paper
visual analog scale, and multi-symptomatic improvement,
Measured with the Fibromyalgia Impact Questionnaire and PGIC.


, Data Highlights ,



results below are based on observed cases the only
Auswertbare patients who responded to the landmark visit. The study million-MD-02,
There were 713 evaluable patients for fibromyalgia syndrome and pain
analysis (n = 236 to 100 mg n = 215 for 200 mg and n = 262 for placebo).


The study FMS - 031, in the three-month visit, there were 549 evaluable patients for the
syndrome (n = 134 to 100 mg n = 259 for 200 mg and
N = 156 for placebo), and 553 evaluable patients for the pain (n = 135
For 100 mg n = 260 for 200 mg and n = 158 for placebo). In the six months
visit, there were 488 evaluable patients for fibromyalgia syndrome
(N = 120 to 100 mg n = 229 for 200 mg and n = 139 for placebo), and
491 evaluable patients for the fibromyalgia pain (n = 121 for 100
Mg n = 230 for 200 mg and n = 140 for placebo).


, Composite responder for fibromyalgia syndrome (pain, PGIC, and
SF-36 PCS) ,
< br> -- A statistically significant number of patients treated with milnacipran
During the study million-MD-02 meets the criteria Composite syndrome Responder
(25% and 26% for the milnacipran 100 mg and 200 mg groups,
) compared to placebo-treated patients (13%).

-- A statistically significant number of patients treated with milnacipran
During the study, FMS - 031 also with the composite syndrome responder criteria
On three months (33% and 33% for the milnacipran 100 mg and 200 mg groups
) compared to placebo-treated patients (17%).
Statistically significant differences table were also observed in the six months
visitors: 33% and 32% of patients met criteria for the responder
milnacipran 100 mg and 200 mg groups, as compared to 19% of
patients in the placebo group.


, Composite responder for fibromyalgia pain (pain and PGIC) ,


-- A statistically a significant number of patients treated with milnacipran
During the study million-MD-02 met the compound pain responder criteria (39%
And 46% in the milnacipran 100 mg and 200 mg groups)
Compared with the placebo-treated patients (25%).

-- A statistically significant number of patients treated with milnacipran
During the study, FMS - 031 also with the pain Composite responder criteria on
Three months (45% and 45% in the milnacipran 100 mg and 200 mg groups,
) compared to placebo-treated patients (27%).
Statistically significant differences table were also observed in the six months
visitors: 44% and 45% of patients with pain Composite Responder
criteria for milnacipran 100 mg and 200 mg, respectively
compared to 28% of patients in the placebo group.


, tolerability ,



milnacipran was generally well tolerated, with the
majority of adverse events (AEs) reported mild to moderate in nature.

-- The most common treatment emergent AEs in the
placebo-controlled clinical trials included nausea (37% versus 20% placebo), headache (18
% vs. 14% placebo), constipation (16% vs. 4% placebo), hot flashes (12% vs. 2%
placebo), hyperhidrosis (9% vs. 2% placebo), vomiting (7% vs
2%), palpitations (7% vs. 2%), heart rate increase (6% vs 1% placebo),
dry mouth (5% versus 2%) and hypertension (5% versus 2%).


-- milnacipran not cause weight gain.


, development plans ,



On 28 September 2005, Forest and Cypress reported that the provisional
top line results from study FMS - 031 not reach statistical significance
. Subsequently, the Food and Drug Administration (FDA) reviewed
your guidelines for the approval of FMS therapies and agreed to the new
companies to evaluate the data on the basis of an updated analysis approach,
, Die a change of LOCF (last observation carried forward),
BOCF (baseline observation carried forward) analysis, as well as other
changes in the use of primary endpoints for the evaluation of effectiveness. By
Revised analysis, a daily dose of 200 mg milnacipran produced statistically
signifiers differences compared to placebo both for the
fibromyalgia syndrome and fibromyalgia pain of the composite endpoints. Even
compared to placebo, a daily dose of 100 mg milnacipran a statistically
signifiers difference in the composite end point fibromyalgia syndrome and
wrong direction significance for the pain of fibromyalgia
composite end point (P =. 056). These data are used as part of the New Drug Application (NDA)
for milnacipran for the treatment of FMS, scheduled for submission to
end of the year 2007.


About Milnacipran ,



Milnacipran is a unique dual reuptake inhibitors, preferably
blocks the reuptake of norepinephrine with a higher potency than serotonin,
two neurotransmitters known to play an essential role in regulating pain
And mood. It was developed for the treatment of depression in more than 32
countries with the real world commercial experience outside the United States
spans more than 10 years and 20 million patient months. Milnacipran is
developed for fibromyalgia in the United States market jointly by Forest
And its licensor, Cypress Biosciences, Inc.
milnacipran was originally developed and sold outside the United States by Pierre Fabre Medicament.


About Fibromyalgia ,



FMS is a chronic and debilitating condition characterized by
widespread pain and stiffness throughout the body, accompanied by severe fatigue, insomnia and mood
symptoms. According to the American College of Rheumatology
, FMS is estimated that more than six million people in the
United States of America. FMS is most often diagnosed in the primary care setting and the
also is the second most commonly diagnosed condition in rheumatology clinics
in the United States after osteoarthritis. Despite the
High prevalence and severity of this syndrome, there are limited treatment options
specifically for FMS in the United States or elsewhere,
And the addressable patient group is not yet well established.


About Cypress ,



Cypress has committed itself as an innovator and market leader in the provision of
products for the treatment of patients with fibromyalgia syndrome. As part
your business development strategy, the company evaluates a number of
proof of concept stage opportunities that leverage their rededication
experience and innovative approach to clinical testing and regulatory
strategy, and the intention to do this on an ongoing basis.
The company continues to evaluate several other potential
strategic transactions, including the potential acquisition of products, product candidates
, technologies and businesses.


For more information about Cypress, please visit Cypress' website
http://www.cypressbio.com.



This press release, as well as Cypress' SEC filings and Website
http://www.cypressbio.com, forward-looking statements in the
meaning of the Private Securities Litigation Reform Act
of 1995, including statements about the potential of milnacipran for the treatment of fibromyalgia syndrome
, and our planned NDA filing for milnacipran. Actual results may
differentiate much of which as a result of a number of factors,
Including those in Cypress' Annual Report on Form 10-K, the most recent
quarterly report on Form 10 - Q and any subsequent SEC filings and
Including, but not limited to, the detailed analysis of the process
results may not be favorable or can lead to different results, the FDA
may not accept our first Phase III the clinical study as one of the two turning
attempts for NDA approval, on further reflection, that we may
Determine, not the submission of a NDA about the end of the year 2007 and even if we do, < br> submit the NDA, that they should not be accepted or not by the FDA,
fact that we may not be able to protect our patent portfolio milnacipran and
that milnacipran may never be approved as a drug by the FDA .


About Forest Laboratories and its products ,



Forest Laboratories (http://www.frx.com), a US-based pharmaceutical company
for the identification, development and delivery of products, which
a positive difference in the lives of people. Forest Laboratories' growing product
Includes Lexapro (R) (escitalopram oxalate), an SSRI
for adults for the initial and maintenance treatment of
depressive disorder and generalized anxiety disorder; Namenda (R) (memantine HCl ), a
N-methyl D-aspartate (NMDA) receptor antagonist for the
treatment of moderate to severe Alzheimer's dementia, and Campral (R)
(Acamprosate Calcium), in combination with psychosocial support
For the maintenance of abstinence from alcohol in patients with alcohol dependence
who are abstinent at treatment initiation.
Addition to our growing product line, Forest also promotes cooperation Daiichi Sankyo, Inc.
products Benicar (R) (olmesartan medoxomil), an angiotensin receptor blocker
, Benicar HCT (R) (olmesartan medoxomil, hydrochlorothiazide ), a
angiotensin receptor blocker and diuretic combination product, and
AZOR (TM) (amlodipine and olmesartan medoxomil)
calcium channel blockers and angiotensin receptor blocker combination product, all for the treatment of
high blood pressure.


Azor is a registered trademark of Daiichi Sankyo, Inc.; Benicar and Benicar HCT
Are registered trademark of Daiichi Sankyo, Inc., and Campral is a registered
trademark of Merck sas, Sante, a subsidiary of Merck KGaA,
Darmstadt, Germany.


With the exception of the historical information contained herein, this release contains forward-looking
"in
meaning of the Private Securities Litigation Reform Act of 1995. These statements include series
risks and uncertainties, including the difficulty of predicting FDA
approvals, the acceptance and demand for new pharmaceutical products, which
impact of competitive products and pricing, the timely development and introduction
new products, and the risk factors from time to time
The Forest Laboratories SEC reports, including the Company's Annual Report
On the Form 10-K for the fiscal year ended March 31, 2007 and on Form 10-Q for
the period ended June 30, 2007.


Forest Laboratories, Inc.

http://www.frx.com