NEW YORK, Nov. 8 /PRNewswire/ -- Total daily dosages of milnacipran
100 mg and 200 mg demonstrated statistically significant and
clinically meaningful improvements in both pain and other core
symptoms associated with fibromyalgia syndrome (FMS), according to
Phase III data presented this week at the 2007 American College of
Rheumatology meeting in Boston, MA. The therapeutic effects of
milnacipran among responders in a six-month study were sustained
for up to one year in a double-blind extension trial. (Logo:
http://www.newscom.com/cgi-bin/prnh/20001011/FORESTLOGO ) Although
widespread chronic pain is the defining characteristic of FMS, it
typically occurs as part of a broader spectrum of symptoms,
including fatigue, cognitive dysfunction, and reduced physical
function. Milnacipran is the first treatment studied for
fibromyalgia whose effectiveness has been evaluated utilizing a
composite responder approach which requires, on a patient-by-
patient basis, concurrent improvements across multiple FMS domains.
As such, composite responder analyses represent a more stringent
assessment of therapeutic effect than the evaluation of individual
symptoms. To be considered a responder for the composite "pain of
fibromyalgia" endpoint, each patient had to demonstrate concurrent
and clinically meaningful improvements in two validated measures:
pain and global impression of disease status. In addition to
meeting those criteria, responders for the composite "treatment of
the fibromyalgia syndrome" endpoint also had to demonstrate
improvement in a third validated measure: physical function. The
results of two Phase III trials showed that milnacipran
demonstrated improvement compared to placebo in treating both the
pain of fibromyalgia, as well as the broader syndrome of
fibromyalgia. Furthermore, data from a six-month extension study
showed that the therapeutic effects of milnacipran were sustained
for up to one year of therapy. "Because patients with fibromyalgia
experience a wide array of symptoms that can overlap with other
conditions, diagnosis and treatment can be complicated. Currently,
many doctors are using multiple medications to treat the 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 not
only relieves pain but addresses the functional and physical
aspects of the illness that can have a significant impact on a
patient's quality of life." Study Methodology In two double-blind,
placebo-controlled, pivotal Phase III studies (Study MLN-MD-02 and
Study FMS-031), the two parallel, primary efficacy assessments
consisted of composite responder analyses for the treatment of both
fibromyalgia syndrome and the pain of fibromyalgia. Pain composite
responders were defined as individuals who achieved both a greater
than or equal to 30% reduction in pain compared to baseline as
measured by a visual analog scale recorded daily on an electronic
patient experience diary, and who rated themselves as "very much
improved" or "much improved" on a Patient Global Impression of
Change (PGIC) scale. Fibromyalgia syndrome composite responders
needed to satisfy the pain composite criteria as well as
demonstrate at least a 6-point improvement in their SF-36 physical
component summary (SF-36 PCS) score. In Study MLN-MD-02, 1196
patients were randomized to receive either milnacipran 100 mg/day
(n=399), 200 mg/day (n=396) or placebo (n=401) over a three-month
period, 67.7% of whom completed the trial. In 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) for six- months,
63.6% of whom completed three-months of treatment, and 57.6% of
whom completed the full six-months of double-blind treatment.
Results were assessed for all patients at both the three- and
six-month visits. Patients who completed the full six-months of
treatment in Study FMS-031 were eligible to enroll in a
multi-center, dose-blinded, extension study designed to evaluate
durability of response up to one year. A total of 449 patients were
either maintained at 200 mg/day (n=209) or re-randomized to 100
mg/day (n=48) or 200 mg/day (n=192) for an additional six months.
Efficacy assessments included change in pain, as measured using a
paper visual analog scale, and multidimensional symptomatic
improvements, as measured using the Fibromyalgia Impact
Questionnaire and PGIC. Data Highlights Results reported below are
based on observed cases, which include only patients who were
evaluable at the landmark visit. In study MLN-MD-02, there were 713
evaluable patients for the fibromyalgia syndrome and pain analyses
(n=236 for 100 mg, n=215 for 200 mg, and n=262 for placebo). In
study FMS-031, at the three-month visit there were 549 evaluable
patients for the syndrome analysis (n=134 for 100 mg, n=259 for 200
mg, and n=156 for placebo), and 553 evaluable patients for the pain
analysis (n=135 for 100 mg, n=260 for 200 mg, and n=158 for
placebo). At the six-month visit there were 488 evaluable patients
for the fibromyalgia syndrome analysis (n=120 for 100 mg, n=229 for
200 mg, and n=139 for placebo), and 491 evaluable patients for the
fibromyalgia pain analysis (n=121 for 100 mg, n=230 for 200 mg, and
n=140 for placebo). Composite responder rates for fibromyalgia
syndrome (pain, PGIC, and SF-36 PCS) -- A statistically significant
number of patients treated with milnacipran during Study MLN-MD-02
met the composite syndrome responder criteria (25% and 26% for the
milnacipran 100 mg and 200 mg groups, respectively) compared to
patients treated with placebo (13%). -- A statistically significant
number of patients treated with milnacipran during Study FMS-031
also met the composite syndrome responder criteria at three months
(33% and 33% for the milnacipran 100 mg and 200 mg groups,
respectively) compared to patients treated with placebo (17%).
Statistically significant differences were also observed at the
six- month visit: 33% and 32% of patients met responder criteria
for the milnacipran 100 mg and 200 mg groups, respectively,
compared to 19% of patients in the placebo group. Composite
responder rates for fibromyalgia pain (pain and PGIC) -- A
statistically significant number of patients treated with
milnacipran during Study MLN-MD-02 met the composite pain responder
criteria (39% and 46% in the milnacipran 100 mg and 200 mg groups,
respectively) compared to patients treated with placebo (25%). -- A
statistically significant number of patients treated with
milnacipran during Study FMS-031 also met the composite pain
responder criteria at three months (45% and 45% in the milnacipran
100 mg and 200 mg groups, respectively) compared to patients
treated with placebo (27%). Statistically significant differences
were also observed at the six- month visit: 44% and 45% of patients
met the composite pain responder criteria in the milnacipran 100 mg
and 200 mg groups, respectively, compared to 28% of patients in
placebo group. Tolerability Milnacipran was generally
well-tolerated, with the majority of adverse events (AEs) reported
being mild to moderate in nature. -- The most common treatment
emergent AEs during the placebo-controlled clinical trials included
nausea (37% vs. 20% placebo), headache (18% vs. 14% placebo),
constipation (16% vs. 4% placebo), hot flushes (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% vs. 2%) and hypertension (5% vs. 2%). -- Milnacipran
did not cause weight gain. Development Plans On September 28, 2005,
Forest and Cypress reported that preliminary top- line results from
Study FMS-031 did not achieve statistical significance.
Subsequently, the Food and Drug Administration (FDA) revised its
guidelines for approval of FMS therapies and agreed to allow the
Companies to re-assess the data based on an updated analysis
approach, which included a change from LOCF (last observation
carried forward) to BOCF (baseline observation carried forward)
analysis as well as other changes in the use of primary endpoints
for efficacy evaluation. Using the revised analyses, a daily dose
of 200 mg milnacipran produced statistically significant
differences compared to placebo for both the fibromyalgia syndrome
and pain of fibromyalgia composite endpoints. Also, compared to
placebo, a daily dose of 100 mg milnacipran produced a
statistically significant difference on the fibromyalgia syndrome
composite endpoint and trended toward significance on the pain of
fibromyalgia composite endpoint (p= .056). These data will be
included as part of the New Drug Application (NDA) for milnacipran
for the treatment of FMS, planned for submission around the end of
2007. The Companies will review these data and the status of the
milnacipran development timeline during an investor call on
Thursday, November 8, 10:00 - 11:00 AM ET. To participate in the
call, please use the following URL:
http://phx.corporate-ir.net/phoenix.zhtml?p=irol-
eventDetails&c=83198&eventID=1686016. (Due to the length of
the link, please copy and paste into your browser.) The webcast can
also be accessed from both the Forest and Cypress corporate
websites: http://www.cypressbio.com/ or http://www.frx.com/. About
Milnacipran Milnacipran is a unique dual-reuptake inhibitor, which
preferentially blocks the reuptake of norepinephrine with higher
potency than serotonin, two neurotransmitters known to play an
essential role in regulating pain and mood. It has been approved
for the treatment of depression in over 32 countries, with
real-world commercial experience outside the U.S. spanning more
than 10 years and 20 million patient-months. Milnacipran is being
developed for fibromyalgia in the United States market jointly by
Forest and its licensor, Cypress Biosciences, Inc. Milnacipran was
originally developed by and is sold outside of the U.S. 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 to affect over six million people in
the United States. FMS is most often diagnosed in the primary care
setting and, in addition, 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 approved
for FMS in the United States or elsewhere, and the addressable
patient population is not yet well established. About Cypress
Cypress is committed to being an innovator and leader in providing
products for the treatment of patients with Fibromyalgia Syndrome.
As part of its business development strategy, the company evaluates
a number of Proof of Concept stage opportunities that leverage its
repurposing experience and innovative approach to clinical trial
design and regulatory strategy, and intend to continue to do this
on an ongoing basis. The company continues to evaluate various
other potential strategic transactions, including the potential
acquisition of products, product candidates, technologies and
companies. For more information about Cypress, please visit
Cypress' website at http://www.cypressbio.com/. This press release,
as well as Cypress' SEC filings and website at
http://www.cypressbio.com/, contain forward-looking statements
within the meaning of the Private Securities Litigation Reform Act
of 1995 including statements about the potential of milnacipran to
treat fibromyalgia syndrome and our planned NDA filing for
milnacipran. Actual results could vary materially from those
described as a result of a number of factors, including those set
forth 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, that more detailed analysis of the
trial results may not be favorable or may lead to different
conclusions; the FDA may not accept our first Phase III clinical
trial as one of the two pivotal trials required for NDA approval,
that upon further reflection that we may determine not to submit an
NDA around the end of 2007 and even if we do submit the NDA, that
it may not be accepted or not approved by the FDA, that we may not
be able to protect our milnacipran patent portfolio 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/) is a US-based pharmaceutical company
dedicated to identifying, developing and delivering products that
make a positive difference in peoples' lives. Forest Laboratories'
growing product line includes Lexapro(R) (escitalopram oxalate), an
SSRI indicated for adults for the initial and maintenance treatment
of major depressive disorder and generalized anxiety disorder;
Namenda(R) (memantine HCl), an N-methyl D- aspartate
(NMDA)-receptor antagonist indicated for the treatment of moderate
to severe Alzheimer's disease; and Campral(R)* (acamprosate
calcium), indicated in combination with psychosocial support for
the maintenance of abstinence from alcohol in patients with alcohol
dependence who are abstinent at treatment initiation. In addition
to our growing product line, Forest also co-promotes the Daiichi
Sankyo, Inc. products Benicar(R)* (olmesartan medoxomil), an
angiotensin receptor blocker, Benicar HCT(R)* (olmesartan
medoxomil-hydrochlorothiazide), an angiotensin receptor blocker and
diuretic combination product, and AZOR(TM)* (amlodipine and
olmesartan medoxomil) a calcium channel blocker and angiotensin
receptor blocker combination product, all indicated for the
treatment of hypertension. *Azor is a trademark of Daiichi Sankyo,
Inc.; Benicar and Benicar HCT are registered trademarks of Daiichi
Sankyo, Inc.; and Campral is a registered trademark of Merck Sante
s.a.s., subsidiary of Merck KGaA, Darmstadt, Germany. Except for
the historical information contained herein, this release contains
"forward-looking statements" within the meaning of the Private
Securities Litigation Reform Act of 1995. These statements involve
a number of risks and uncertainties, including the difficulty of
predicting FDA approvals, the acceptance and demand for new
pharmaceutical products, the impact of competitive products and
pricing, the timely development and launch of new products, and the
risk factors listed from time to time in the Forest Laboratories'
SEC reports, including the Company's Annual Report on Form 10-K for
the fiscal year ended March 31, 2007, and on Form 10-Q for the
period ended June 30, 2007.
http://www.newscom.com/cgi-bin/prnh/20001011/FORESTLOGO
http://photoarchive.ap.org/ DATASOURCE: Forest Laboratories, Inc.
and Cypress Bioscience, Inc. CONTACT: Charles Triano, Vice
President - Investor Relations of Forest Laboratories, Inc.,
+1-212-224-6714, ; Sabrina Martucci Johnson, CFO, CBO, Ex. VP, or
Mary Gieson, Investor Relations, +1-858-452-2323, , both of Cypress
Bioscience, Inc. Web site: http://www.frx.com/
http://www.cypressbio.com/
http://www.rheumatology.org/annual/index.asp Company News On-Call:
http://www.prnewswire.com/comp/329163.html
http://www.prnewswire.com/comp/638922.html
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