Phase III Data to be Presented at American College of Rheumatology
Annual Meeting Further Demonstrate Efficacy and Safety of Savella for
the Management of Fibromyalgia
NEW YORK & SAN DIEGO--(BUSINESS WIRE)--Oct. 17, 2009--
Forest Laboratories, Inc. (NYSE: FRX) and Cypress Bioscience, Inc.
(NASDAQ: CYPB) today announced that Savella® (milnacipran HCI) 100
mg/day (50 mg twice daily) demonstrated statistically significant and
clinically meaningful concurrent improvements in pain, patient global
assessment, and physical function, according to results from a
large-scale, Phase III clinical trial that will be presented on Tuesday,
October 20, 2009, at the American College of Rheumatology Annual Meeting
in Philadelphia, PA. 100 mg/day is the recommended dose of Savella.
Savella is a selective serotonin and norepinephrine dual reuptake
inhibitor (SNRI) that was approved by the U.S. Food and Drug
Administration (FDA) earlier this year for the management of
fibromyalgia.
Fibromyalgia is a chronic condition characterized by widespread pain and
decreased physical function, afflicting as many as six million people in
the United States. The study showed statistically significant and
clinically meaningful concurrent improvements in pain, patient global
assessment, and physical function, among patients receiving Savella
treatment of 100 mg/day, as compared to a placebo treatment group, when
measured by patient-reported outcomes assessed in composite responder
analyses. These results at the 100 mg/day dose are consistent with those
of previous clinical trials that have demonstrated the safety and
efficacy of Savella at doses of 100 mg/day and 200 mg/day.
"Fibromyalgia is a common, chronic pain disorder that can be associated
with an array of debilitating symptoms, so it is important that
treatments manage the multiple symptoms of fibromyalgia and improve
function," said lead investigator, Lesley M. Arnold, MD, Professor of
Psychiatry, University of Cincinnati College of Medicine.
Study Details
This Phase III, double-blind, placebo-controlled trial of 1,025
fibromyalgia patients was designed to further evaluate the efficacy and
tolerability of Savella 100 mg/day. Patients were randomized to receive
Savella 100 mg/day (n=516) or placebo (n=509) and underwent four to six
weeks of flexible dose escalation, followed by 12 weeks of stable-dose
treatment followed by a two-week randomized, double-blind
discontinuation phase.
This study, like other phase III fibromyalgia studies of Savella used a
composite responder analysis as the primary endpoint. This endpoint
required individual patients to demonstrate concurrent and clinically
meaningful improvements in multiple domains using validated measures,
including pain (visual analog scale), patient global assessment (patient
global impression of change), and physical function (Short Form-36
Physical Component Summary).
In this study a greater proportion of patients in the Savella treatment
arm (100 mg/day) as compared with placebo treatment, at 3 months,
experienced at least a 30% reduction in pain from baseline and also
rated themselves as "very much improved" or "much improved" based on the
patient global assessment. In addition, a greater proportion of patients
treated with Savella as compared with placebo treatment met the criteria
for a treatment response as measured by concurrent improvements in pain,
patient global assessment, and physical function. Some patients who
rated themselves as globally "much" or "very much" improved experienced
a decrease in pain as early as week 1 of treatment with a stable dose of
Savella that persisted throughout the study.
“These data confirm the benefits of Savella in managing fibromyalgia,”
said Dr. Marco Taglietti, President of Forest Research Institute.
“Patients receiving Savella showed simultaneous improvements on multiple
measures of fibromyalgia, including pain, patient global assessment, and
physical function.”
Savella was generally well tolerated in the study. The most common
treatment emergent adverse events observed during the placebo-controlled
trial included nausea, headache, constipation, hot flush, dizziness,
insomnia, hyperhidrosis, palpitations, fatigue, tachycardia, and
hypertension. The majority of adverse reactions reported were mild to
moderate in nature.
Overall premature discontinuation rates (all causes, including those
related to adverse events) through the stable-dose treatment period of
the trial were similar for patients receiving 100 mg/day of Savella and
patients receiving placebo.
About Savella
Savella was approved by the FDA on January 14, 2009, for the management
of fibromyalgia, a chronic condition characterized by widespread pain
and decreased physical function that afflicts as many as six million
people in the United States. Savella is a dual-reuptake inhibitor that,
in vitro, preferentially blocks the reuptake of norepinephrine with
higher potency than for serotonin, two neurotransmitters thought to a
play a central role in the symptoms of fibromyalgia. Savella is marketed
by Forest and its licensor, Cypress Bioscience. Pierre Fabre, who
originally developed and sells milnacipran outside the U.S., licensed
the rights for North America to Cypress Bioscience.
Please visit www.savella.com
for more information.
Important Safety Information
Savella is a selective serotonin and norepinephrine reuptake
inhibitor (SNRI), similar to some drugs used for the treatment of
depression and other psychiatric disorders. Antidepressants increased
the risk compared to placebo of suicidal thinking and behavior
(suicidality) in children, adolescents, and young adults in short-term
studies of major depressive disorder (MDD) and other psychiatric
disorders. Anyone considering the use of such drugs in a child,
adolescent, or young adult must balance this risk with the clinical
need. Short-term studies did not show an increase in the risk of
suicidality with antidepressants compared to placebo in adults beyond
age 24; there was a reduction in risk with antidepressants compared to
placebo in adults aged 65 and older. Depression and certain other
psychiatric disorders are themselves associated with increases in the
risk of suicide. Patients of all ages who are started on Savella should
be monitored appropriately and observed closely for clinical worsening,
suicidality, or unusual changes in behavior, especially during the
initial few months of drug therapy or at times of dose changes, either
increases or decreases. Families and caregivers should be advised of the
need for close observation and communication with the prescriber.
Savella is not approved for use in the treatment of major depressive
disorder. Savella is not approved for use in pediatric patients.
Contraindications
Savella is contraindicated in patients taking monoamine oxidase
inhibitors (MAOIs) concomitantly or within 14 days of discontinuing
treatment with an MAOI. There have been reports of serious, sometimes
fatal, reactions in patients started on an MAOI who were receiving or
had recently discontinued a serotonin reuptake inhibitor. At least 5
days should be allowed after stopping Savella before starting an MAOI.
Savella is contraindicated in patients with uncontrolled narrow-angle
glaucoma and should be used with caution in patients with controlled
narrow-angle glaucoma. In clinical trials, Savella was associated with
an increased risk of mydriasis.
Warnings and Precautions
Prescriptions for Savella should be written for the smallest quantity of
tablets, consistent with good patient management, in order to reduce the
risk of overdose.
Development of a potentially life-threatening serotonin syndrome or
neuroleptic malignant syndrome (NMS)-like reactions have been reported
with SSRIs and SNRIs alone, including Savella, but particularly with
concomitant use of serotonergic drugs (including triptans), drugs that
impair metabolism of serotonin (including MAOIs), or antipsychotics or
other dopamine antagonists. The management of these reactions should
include immediate discontinuation of Savella and the concomitant agent
and supportive symptomatic treatment. The concomitant use of Savella
with serotonin precursors is not recommended.
SNRIs, including Savella, have been associated with cardiovascular
effects, including cases of elevated blood pressure, requiring immediate
treatment. In clinical trials, sustained increases in systolic and
diastolic blood pressure occurred more frequently in Savella-treated
patients compared to placebo. Among patients who were non-hypertensive
at baseline, approximately twice as many patients receiving Savella, vs
placebo, became hypertensive at the end of the study. Clinically
significant increases in pulse (≥20 bpm) occurred more frequently in
Savella-treated than placebo-treated patients. Blood pressure and heart
rate should be monitored prior to initiating treatment with Savella and
periodically throughout treatment. Pre-existing hypertension,
tachyarrhythmias, and other cardiac diseases should be treated before
starting therapy with Savella. Savella should be used with caution in
patients with significant hypertension or cardiac disease. Concomitant
use of Savella with drugs that increase blood pressure and pulse has not
been evaluated, and such combinations should be used with caution. For
patients who experience a sustained increase in blood pressure or heart
rate while receiving Savella, either dose reduction or discontinuation
should be considered.
Savella should be prescribed with caution in patients with a history of
seizure disorder or mania.
Savella has been associated with mild elevations of ALT and AST (1 to 3
times the upper limit of normal). Rarely, reports of serious liver
injury, including fulminant hepatitis, have been reported in patients
treated with milnacipran. Savella should be discontinued in patients who
develop jaundice or other evidence of liver dysfunction and should not
be resumed unless another cause can be established.
As with other SNRIs and SSRIs, withdrawal symptoms have been observed
following discontinuation of milnacipran. A gradual dose reduction is
recommended.
Hyponatremia may occur as a result of treatment with SSRIs and SNRIs,
including Savella. Elderly patients may be at greater risk.
Discontinuation should be considered for patients with symptomatic
hyponatremia.
SSRIs and SNRIs, including Savella, may increase the risk of bleeding
events. Patients should be cautioned regarding the risk of bleeding
associated with concomitant use of Savella and NSAIDs, aspirin,
warfarin, or other drugs that affect coagulation.
Savella can affect urethral resistance and micturition. Caution is
advised in the use of Savella in patients with a history of dysuria,
notably in male patients with a history of obstructive uropathies as
these patients may experience higher rates of genitourinary adverse
events.
Savella should ordinarily not be prescribed to patients with substantial
alcohol use or evidence of chronic liver disease.
Use in Specific Populations
There are no adequate and well-controlled studies in pregnant women.
Savella should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus.
Adverse Reactions
In clinical trials, the most frequently occurring adverse reaction was
nausea (37% vs 20% for placebo). The most commonly occurring adverse
reactions (≥5% and greater than placebo) were headache (18% vs 14%),
constipation (16% vs 4%), dizziness (10% vs 6%), insomnia (12% vs 10%),
hot flush (12% vs 2%), hyperhidrosis (9% vs 2%), vomiting (7% vs 2%),
palpitations (7% vs 2%), heart rate increased (6% vs 1%), dry mouth (5%
vs 2%), and hypertension (5% vs 2%).
About Forest Laboratories
Forest Laboratories (NYSE: FRX) is a U.S.-based pharmaceutical company
with a long track record of building partnerships and developing and
marketing products that make a positive difference in people's lives. In
addition to its well-established franchises in therapeutic areas of the
central nervous and cardiovascular systems, Forest's current pipeline
includes product candidates in all stages of development and across a
wide range of therapeutic areas. The company is headquartered in New
York, NY. To learn more about Forest Laboratories, visit www.FRX.com.
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 Forest Laboratories' Annual Report on Form
10-K, Quarterly Report on Form 10-Q, and any subsequent SEC filings.
About Cypress Bioscience
Cypress Bioscience, Inc. provides therapeutics and personalized medicine
services, facilitating improved and individualized patient care. Cypress
addresses the evolving needs of specialist physicians and their patients
by identifying unmet medical needs in the areas of pain, rheumatology,
and physical medicine and rehabilitation, including challenging
disorders such as fibromyalgia and rheumatoid arthritis. This approach
to improving patient care creates a unique partnership with physicians.
Current products include Savella® (milnacipran HCI) and the Avise PGSM
and Avise MCVSM therapeutic monitoring, diagnostic and prognostic tests
for rheumatoid arthritis.
For more information about Cypress, please visit the Company's website
at www.cypressbio.com.
This press release, as well as Cypress' SEC filings and website at www.cypressbio.com,
contain forward-looking statements within the meaning of the Private
Securities Litigation Reform Act of 1995. Such statements include, but
are not limited to, statements regarding the potential of Savella to
treat fibromyalgia and the ability of Savella to provide meaningful
improvements in pain, patient global assessment and physical function
among patients being treated for fibromyalgia. 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, its
most recent Quarterly Report on Form 10-Q and any subsequent SEC filings
and including, but limited to, that more detailed analysis of the trial
results may not be favorable or may lead to different conclusions, that
Savella’s efficacy for treating fibromyalgia may be perceived
differently among doctors, patients and third-party payors than the
trial results and that Savella may not meet with market acceptance.
These forward-looking statements speak only as of the date hereof and
Cypress disclaims any intention or obligation to update or revise any
forward-looking statements, whether as a result of new information,
future events or otherwise, except as required by law.
About Pierre Fabre
Pierre Fabre group, France's second biggest independent pharmaceutical
laboratory, achieved a turnover of 1.75 billion euros in 2008.
Approximately 10,000 people including 1,400 in the research sector, are
employed Its therapeutic are ethical products, healthcare products and
dermocosmetics with the brands Avene, Ducray, A Derma, Galenic, Klorane
and Rene Furterer. In 2008, Pierre Fabre Medicament dedicated 33% of its
annual turnover to R&D in five main therapeutic directions: oncology,
the Central Nervous System, cardiology, internal medicine/urology and
dermatology.
To learn more about the Pierre Fabre group, visit www.pierre-fabre.com.
Source: Forest Laboratories, Inc. and Cypress Bioscience, Inc.
Forest Laboratories, Inc.
Frank J. Murdolo, 212-224-6714
Vice
President - Investor Relations
Frank.Murdolo@frx.com
or
Cypress
Bioscience, Inc.
Mary Gieson, 858-452-2323
Investor Relations
mgieson@cypressbio.com