Forest Laboratories, Inc. (NYSE: FRX) and Pierre Fabre
Laboratories announced today that FETZIMA™ (levomilnacipran
extended-release capsules), a once-daily serotonin and
norepinephrine reuptake inhibitor (SNRI), discovered by Pierre
Fabre Laboratories and co-developed by Forest Laboratories, Inc.
was approved by the U.S. Food and Drug Administration (FDA) for the
treatment of Major Depressive Disorder (MDD) in adults.
FETZIMA 80 mg bottle (Photo: Business
Wire)
Major Depressive Disorder, also known as depression, is a common
debilitating disorder in which feelings of sadness and other
symptoms interfere with a person’s ability to work, sleep, study,
eat, and enjoy once-pleasurable activities. MDD affects almost 16
million adults in the United States every year, with a range of
severity from mild to severe.
In the placebo-controlled, pivotal Phase III studies of adult
patients with MDD, statistically significant and clinically
meaningful improvement in depressive symptoms (primary endpoint)
was demonstrated across three FETZIMA dosage strengths of 40, 80,
and 120 mg once daily compared with placebo as measured by the
Montgomery Åsberg Depression Rating Scale (MADRS) total score
(primary endpoint). FETZIMA also demonstrated superiority over
placebo as measured by improvement in the Sheehan Disability Scale
(SDS) functional impairment total score (secondary endpoint).
“Because people respond differently to different medications,
Forest Laboratories is dedicated to bringing a range of treatment
possibilities to adults living with MDD, as part of our growing
mental health portfolio,” said Howard Solomon, Chairman, Chief
Executive Officer and President of Forest Laboratories.
“The approval of FETZIMA fulfills that commitment to the millions
of people living with MDD.”
"We are proud that another product stemming from Pierre Fabre’s
research has received approval in the United States. This marketing
authorisation represents a key milestone for our laboratory, and it
confirms our choice to make neuropsychiatry a strategic axis of our
R&D efforts, next to oncology and dermatology," said Frédéric
Duchesne, President Pharmaceutical Division, Pierre Fabre
Laboratories.
The most common adverse reactions (incidence ≥5% and at least
twice the rate of placebo) in the placebo-controlled trials were
nausea, constipation, hyperhidrosis, heart rate increased, erectile
dysfunction, tachycardia, vomiting, and palpitations. Rates of
adverse events were generally consistent across doses (40-120 mg);
the only dose-related adverse events (greater than 2% overall
incidence) were urinary hesitation and erectile dysfunction.
“As many people with MDD struggle to find a treatment that works
for them, FETZIMA provides patients and physicians with an
additional option for treating this serious disease,” said Michael
Liebowitz, MD, Professor of Clinical Psychiatry at Columbia
University.
Forest Laboratories Inc. expects FETZIMA to be available to
wholesalers in the 4th calendar quarter 2013.
Data Highlights
The efficacy of FETZIMA was demonstrated in three positive
double-blind Phase III studies comprising two fixed-dose studies
and one flexible-dose study that compared FETZIMA to placebo in
adults with MDD. A total of more than 1,600 adult patients received
a once-daily dose of either FETZIMA (40, 80, 120mg) or placebo in
the three studies. In each study, the primary endpoint was change
from baseline to endpoint in the Montgomery Åsberg Depression
Rating Scale (MADRS) total score and the secondary endpoint was
change from baseline to endpoint in the Sheehan Disability Scale
(SDS) total score. In all three studies, statistically significant
improvement was seen for the FETZIMA group compared with placebo on
both the primary and secondary endpoints using both the
mixed-effects model for repeated measures (MMRM) and
last-observation-carried-forward (LOCF) analyses.
Primary Endpoint MADRS (Reduction in depressive symptoms)
In all three studies, FETZIMA demonstrated superiority over
placebo in the improvement of depressive symptoms as measured by
the change from baseline to Week 8 in the MADRS total score. MADRS
is a widely used, clinician-rated scale to assess the severity of
10 depressive symptoms. A total MADRS score of 35 or greater is
suggestive of severe depression. The primary efficacy endpoint in
the pivotal trials was change from baseline to week 8 in the total
MADRS score. A 2-point difference between drug effect and placebo
is generally considered to represent a clinically meaningful
improvement in depressive symptoms.
For study 1, the mean baseline MADRS total score was 36 for all
treatment groups. The LS mean difference from placebo in change
from baseline was statistically significant at all three FETZIMA
doses (-3.2 at 40 mg/day, -4.0 at 80 mg/day, and -4.9 at 120
mg/day). For study 2, the mean baseline MADRS total score was 31
for all treatment groups. The LS mean difference from placebo in
change from baseline was statistically significant at both FETZIMA
doses studied (-3.3 at 40 mg/day, -3.1 at 80 mg/day). For study 3,
the mean baseline MADRS total score was 35 for all treatment
groups. The LS mean difference from placebo in change from baseline
was statistically significant for the FETZIMA dosing range studied
(-3.1 at 40-120 mg/day).
Secondary Endpoint SDS (Improvement in functional
impairment)
FETZIMA also demonstrated superiority over placebo as measured
by improvement in the Sheehan Disability Scale (SDS) functional
impairment total score. SDS is a validated scale that measures the
extent that emotional symptoms disrupt patient functioning in 3
life domains: work/school, social life, and family life with each
item scored from 0 (unimpaired) to 10 (highly impaired).
About Major Depressive Disorder
MDD is a serious medical condition often requiring treatment,
affecting almost 16 million adults in the United States yearly or
approximately 7.3% of the adult U.S. population. MDD, also known as
depression, is a common debilitating disorder in which feelings of
sadness and other symptoms occur nearly every day for at least two
weeks and interfere with a person’s ability to work, sleep, study,
eat, and enjoy once-pleasurable activities. Depression costs the
U.S. an estimated $44 billion each year. Among all medical
illnesses, MDD is a leading cause of disability in the U.S. The
World Health Organization predicts depression will become the
second leading cause of disability by the year 2020.
About FETZIMA
FETZIMA is a serotonin and norepinephrine reuptake inhibitor
(SNRI) indicated for the treatment of Major Depressive Disorder
(MDD). The recommended therapeutic dose range for FETZIMA is 40 mg
to 120 mg once daily and can be taken with or without food.
While the exact mechanism is unknown, it is thought to be
related to the potentiation of serotonin and norepinephrine in the
central nervous system, through inhibition of reuptake at serotonin
and norepinephrine transporters. Non-clinical studies have shown
that FETZIMA is a potent and selective serotonin and norepinephrine
reuptake inhibitor.
Levomilnacipran was licensed to Forest Laboratories Inc. by
Pierre Fabre, in the U.S. and Canada. Pierre-Fabre will also be the
active pharmaceutical ingredient (API) supplier.
Visit FETZIMA.com for more
information on this once-daily option for the treatment of MDD in
adults.
FETZIMA Indication and Usage
FETZIMA is a serotonin and norepinephrine reuptake inhibitor
(SNRI) indicated for the treatment of Major Depressive Disorder
(MDD).
FETZIMA is not approved for the management of fibromyalgia.
Efficacy and safety of FETZIMA for the management of fibromyalgia
have not been established.
Important Safety Information
WARNING: SUICIDAL THOUGHTS AND
BEHAVIORS
Antidepressants increased the risk of suicidal thoughts and
behavior in children, adolescents, and young adults in short-term
studies. These studies did not show an increase in the risk of
suicidal thoughts and behavior with antidepressant use in patients
over age 24; there was a reduction in risk with antidepressant use
in patients aged 65 and older.
In patients of all ages who are started on antidepressant
therapy, monitor closely for worsening, and for emergence of
suicidal thoughts and behaviors. Advise families and caregivers of
the need for close observation and communication with the
prescriber. FETZIMA is not approved for use in pediatric
patients.
Contraindications
- FETZIMA is contraindicated in patients
with a hypersensitivity to levomilnacipran, milnacipran HCl, or to
any excipient in the formulation.
- The use of MAOIs intended to treat
psychiatric disorders with FETZIMA or within 7 days of stopping
treatment with FETZIMA is contraindicated due to an increased risk
of serotonin syndrome. The use of FETZIMA within 14 days of
stopping an MAOI intended to treat psychiatric disorders is also
contraindicated.
- Starting FETZIMA in a patient who is
being treated with MAOIs such as linezolid or intravenous methylene
blue is also contraindicated due to an increased risk of serotonin
syndrome.
- Do not use FETZIMA in patients with
uncontrolled narrow-angle glaucoma.
Warnings and Precautions
- All patients being treated with
antidepressants should be monitored appropriately and observed
closely for clinical worsening, suicidality, and unusual changes in
behavior, especially during the first few months of treatment and
when increasing or decreasing the dose. Consider changing the
therapeutic regimen, including possibly discontinuing the
medication, in patients whose depression is persistently worse or
includes symptoms of anxiety, agitation, panic attacks, insomnia,
irritability, hostility, aggressiveness, impulsivity, akathisia,
hypomania, mania, or suicidality that are severe, abrupt in onset,
or were not part of the patient's presenting symptoms. Families
and caregivers of patients being treated with antidepressants
should be alerted about the need to monitor patients daily.
Prescriptions for FETZIMA should be written for the smallest
quantity of capsules consistent with good patient management, in
order to reduce the risk of overdose.
- Serotonin Syndrome: The
development of a potentially life-threatening serotonin syndrome
has been reported with SNRIs and SSRIs both when taken alone, but
especially when co-administered with other serotonergic agents
(including triptans, tricyclic antidepressants, fentanyl, lithium,
tramadol, tryptophan, buspirone, and St. John’s Wort) and with
drugs that impair metabolism of serotonin (in particular, MAOIs,
both those intended to treat psychiatric disorders and also others,
such as linezolid and intravenous methylene blue). Symptoms of
serotonin syndrome may include mental status changes (eg,
agitation, hallucinations, delirium, and coma), autonomic
instability (eg, tachycardia, labile blood pressure, diaphoresis,
flushing, hyperthermia), neuromuscular symptoms (eg, tremor,
rigidity, myoclonus, hyperreflexia, incoordination), seizures,
and/or gastrointestinal symptoms. If symptoms of serotonin syndrome
occur, discontinue FETZIMA and initiate supportive treatment. If
concomitant use of FETZIMA with other serotonergic drugs is
clinically warranted, patients should be aware of a potential
increased risk for serotonin syndrome, particularly during
treatment initiation and dose increases.
- SNRIs, including FETZIMA, have been
associated with increases in blood pressure. Blood pressure should
be measured prior to initiating treatment and periodically
throughout FETZIMA treatment. Pre-existing hypertension should be
controlled before initiating treatment with FETZIMA. For patients
who experience a sustained increase in blood pressure,
discontinuation or other appropriate medical intervention should be
considered.
- SNRIs including FETZIMA have been
associated with an increase in heart rate. Heart rate should be
measured prior to initiating treatment and periodically throughout
FETZIMA treatment. Pre-existing tachyarrhythmias and other cardiac
disease should be treated before starting therapy with FETZIMA. For
patients who experience a sustained increase in heart rate,
discontinuation or other appropriate medical intervention should be
considered.
- SSRIs and SNRIs, including FETZIMA, may
increase the risk of bleeding events, some serious. Concomitant use
of aspirin, warfarin, NSAIDs and other anticoagulants may add to
this risk.
- Mydriasis has been reported in
association with SNRIs including FETZIMA; therefore, FETZIMA should
be used with caution in patients with controlled narrow-angle
glaucoma. Patients with raised intraocular pressure should be
monitored. DO NOT use FETZIMA in patients with uncontrolled
narrow-angle glaucoma.
- SNRIs, including FETZIMA, can affect
urethral resistance. Caution is advised when using FETZIMA in
patients prone to obstructive urinary disorders.
- Symptoms of mania/hypomania were
reported in 0.2% of FETZIMA-treated patients and 0.2% of
placebo-treated patients in clinical studies. As with all
antidepressants, FETZIMA should be used cautiously in patients with
a history or family history of bipolar disorder, mania or
hypomania. Prior to initiating treatment with FETZIMA, patients
should be adequately screened to determine if they are at risk for
bipolar disorder. FETZIMA is not approved for use in treating
bipolar depression.
- FETZIMA should be prescribed with
caution in patients with a seizure disorder.
- Discontinuation symptoms, some serious,
have been reported with discontinuation of serotonergic
antidepressants such as FETZIMA. Gradual dose reduction is
recommended, instead of abrupt discontinuation, whenever possible.
Monitor patients when discontinuing FETZIMA. If intolerable
symptoms occur following a dose decrease or upon discontinuation of
treatment, consider resuming the previously prescribed dose and
decreasing the dose at a more gradual rate.
- Advise patients that if they are
treated with diuretics or are otherwise volume depleted, or are
elderly, they may be at greater risk of developing hyponatremia
while taking FETZIMA. Although no cases of hyponatremia resulting
from FETZIMA treatment were reported in the clinical studies,
hyponatremia has occurred as a result of treatment with SSRIs and
SNRIs. FETZIMA should be discontinued in patients with symptomatic
hyponatremia and appropriate medical intervention should be
instituted.
Adverse Reactions
- The most commonly observed adverse
reactions in MDD patients treated with FETZIMA in
placebo-controlled studies (incidence ≥5% and at least twice the
rate of placebo) were: nausea, constipation, hyperhidrosis, heart
rate increased, erectile dysfunction, tachycardia, vomiting, and
palpitations.
About Pierre Fabre
Pierre Fabre Laboratories, the second largest independent
pharmaceutical group in France, achieved a turnover of 1.98 billion
Euros in 2012, with international sales accounting for 54%. Pierre
Fabre has branches in 42 countries and its products are distributed
in over 130 countries.
Through the holding company Pierre Fabre Participations, 65% of
Pierre Fabre SA is held by the Pierre Fabre Foundation, recognized
as a public utility since 1999. In addition, thanks to an employee
shareholding program set up in 2005, 90% of the company’s employees
collectively have a 7 % shareholding interest. This original
governance program ensures the independence and sustainability of
the company.
Their activities cover all aspects of healthcare, from
prescription drugs and family health products to dermo-cosmetics.
Pierre Fabre Laboratories employ some 10,000 people worldwide,
1,400 of whom are dedicated to R&D. Every year, the group
allocates 20% of its drug revenues to R&D, focusing on three
main areas: oncology, dermatology and neuropsychiatry.
With brands including Avène, Glytone, A-Derma, Ducray, Galénic,
Klorane, Naturactive, René Furterer or Pierre Fabre Oral Care,
Pierre Fabre Laboratories are France’s market leaders when it comes
to skin, hair and oral care products sold in the pharmacy channel.
Avène is marketed in over 100 countries, and is the leading
dermo-cosmetics brand in Europe, Japan and China. In prescription
drugs, Pierre Fabre focuses on four therapeutic areas: oncology,
dermatology, neuropsychiatry and women’s health. In oncology,
Pierre Fabre achieves about 90% of its turnover outside its home
country.
In 2012, Pierre Fabre Laboratories was audited by the French
certification group AFNOR at advanced level for its corporate
social responsibility (CSR) performance. To learn more, visit
www.pierre-fabre.com.
About Forest Laboratories, Inc.
Forest Laboratories' (NYSE: FRX) longstanding global
partnerships and track record developing and marketing
pharmaceutical products in the United States have yielded its
well-established central nervous system and cardiovascular
franchises and innovations in anti-infective, respiratory,
gastrointestinal and pain management medicine. Forest’s pipeline,
the most robust in its history, includes product candidates in all
stages of development across a wide range of therapeutic areas. The
Company is headquartered in New York, NY. To learn more, 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 Reports on Form
10-Q, and any subsequent SEC filings. Forest assumes no obligation
to update forward-looking statements contained in this release to
reflect new information or future events or developments.
Photos/Multimedia Gallery Available:
http://www.businesswire.com/multimedia/home/20130725006648/en/
Forest Laboratories, Inc.Frank J. Murdolo, 212-224-6714Vice
President – Investor Relationsmedia.relations@frx.com
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