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.
SOURCE Forest Laboratories, Inc. and Cypress Bioscience, Inc.
 back to top
Related links:
http://www.frx.com
http://www.cypressbio.com
http://www.rheumatology.org/annual/index.asp
Photo Notes:
NewsCom: http://www.newscom.com/cgi-bin/prnh/20001011/FORESTLOGO
AP Archive: http://photoarchive.ap.org
PRN Photo Desk, photodesk@prnewswire.com
http://www.prnewswire.com/comp/329163.html
http://www.prnewswire.com/comp/638922.html /
CONTACT:
Charles Triano, Vice President - Investor
Relations of Forest Laboratories, Inc., +1-212-224-6714,
Charles.Triano@frx.com; Sabrina Martucci Johnson, CFO, CBO, Ex.
VP, or Mary Gieson, Investor Relations, +1-858-452-2323,
Mgieson@cypressbio.com, both of Cypress Bioscience, Inc.
|
