Forest Laboratories and Almirall Announce Positive Results for the Second Phase III Study for Aclidinium and Formoterol

  Forest Laboratories and Almirall Announce Positive Results for the Second
  Phase III Study for Aclidinium and Formoterol combination in COPD

  *Aclidinium/formoterol demonstrates consistent, statistically significant
    lung function improvement in the second pivotal efficacy trial
  *Positive outcomes also were seen in TDI (breathlessness) and SGRQ (quality
    of life) in this study
  *Regulatory filings with the United States Food & Drug (FDA) and European
    Medical Authority (EMA) are planned in Q4 2013

Business Wire

NEW YORK & BARCELONA -- May 1, 2013

Forest Laboratories, Inc. (NYSE:FRX) and Almirall, S.A. (ALM:MC) today
announced positive topline results from AUGMENT COPD, the second six-month
pivotal phase III clinical trial evaluating the efficacy and safety of
investigational fixed dose combinations of aclidinium bromide (LAMA) and
formoterol fumarate (LABA), delivered in the Pressair^® (Genuair^® outside the
USA) inhaler.

The 400/12mcg combination of aclidinium/formoterol demonstrated statistically
significant improvements in change from baseline for the co-primary endpoints
of Forced Expiratory Volume (FEV1) at 1 hour post-dose versus aclidinium
400mcg (P<0.0001) and morning predose trough FEV1 versus formoterol 12mcg at
week 24 (P<0.05). The 400/6mcg combination demonstrated statistically
significant improvements in (FEV1) at 1 hour post-dose versus aclidinium
400mcg (p<0.0001). For the change from baseline in morning pre-dose trough
FEV1, the 400/6mcg combination did not reach significance versus formoterol
12mcg at week 24 (p>0.05).

Both combinations of aclidinium/formoterol (400/12mcg and 400/6mcg) provided
statistically significant improvements versus placebo in the above two
comparisons (both p<0.0001).

The positive results of the aclidinium/formoterol 400/12mcg combination in
this study are consistent with the statistically significant improvement in
lung function demonstrated by aclidinium/formoterol 400/12mcg in the
previously completed ACLIFORM/COPD Phase III study. In both studies, the
400/12mcg dose successfully met the required regulatory “Combination Rule” for
testing two or more drugs combined in a single dosage form.

Both studies included secondary end points. The end points analyzed to date
are change from baseline vs placebo at 24 weeks in TDI (Transitional Dyspnea
Index, which measures breathlessness) and in SGRQ (St. George’s Respiratory
Questionnaire, a respiratory-specific disease-related quality of life
assessment). Positive outcomes were seen with the two combinations achieving
the MCID (Meaningful Clinical Important Difference) of a one point change
(p<0.0001) in TDI in both studies, and a four point change (p<0.0001) in
SGRQin the AUGMENT/COPD study. Additional analyses, including those on pooled
data, will be presented at future scientific meetings.

Additionally, both aclidinium/formoterol treatment arms were well-tolerated in
this study. The most common adverse events (greater than or equal to 3% and
reported more frequently with either aclidinium/formoterol 400/12mcg or
aclidinium/formoterol 400/6mcg than placebo respectively) were: cough (5.1%,
3.9% and 3.6%); nasopharyngitis (4.8%, 5.1% and 3.6%); headache (4.8%, 4.2%
and 3.3%); urinary tract infection (4.5%, 2.1% and 3.0%); upper respiratory
tract infection (3.0%, 3.9% and 1.5%); back pain (3.0%, 1.5% and
2.7%);diarrhea (2.7% 3.0% and 2.4%); nausea (1.5%, 4.5% and 1.2%); and dyspnea
(1.5%, 3.3% and 1.8%).

“By successfully achieving the primary endpoints in these two pivotal trials,
we have demonstrated that aclidinium/formoterol, 400/12mcg, delivers
statistically significant improvement in lung function” said Dr. Marco
Taglietti, President of Forest Research Institute. “The success of this phase
III program supports the potential of aclidinium/formoterol as a new treatment
option for COPD patients who could benefit from the enhanced bronchodilation
of two complementary, proven therapies.”

“We are very pleased with these results which confirm the efficacy and safety
profile of the novel combination of aclidinium/formoterol”, commented Dr.
Bertil Lindmark, Chief Scientific Officer at Almirall. The positive results in
breathlessness and quality of life measures combined with the patient
preferred Pressair/Genuair multidose device could place this new combination
as a treatment option for patients suffering from COPD. The successful
completion of both pivotal studies mark an important milestone towards
achieving an innovative global respiratory franchise around aclidinium and the
Genuair inhaler.”

Regulatory filings in the USA (FDA) and Europe (EMA) are planned in Q4 2013.

About AUGMENT/COPD Phase III Study

AUGMENT (Aclidinium/formoterol FUmurate Combination for InvestiGative use in
the TreatMENT of Moderate to Severe COPD) was a 24-week randomized
double-blind trial evaluating the 400/12mcg and 400/6mcg fixed dose
combinations of aclidinium bromide/formoterol fumarate compared with
aclidinium bromide 400mcg, formoterol fumarate 12mcg and placebo administered
BID through the Pressair inhaler (Genuair outside the USA) in 1692 patients
with moderate to severe COPD in the USA, Australia and New Zealand.

Two co-primary endpoints, designed to take in account the different
contributions of the individual components in terms of efficacy, were
developed in consultation with FDA/EMA to meet the “Combination Rule” (i.e.,
showing superiority in FEV1 at week 24 of the fixed dose combination over
aclidinium at one hour post-dose and over formoterol at morning pre-dose
trough):

1. The first co-primary endpoint consisted of the comparison between the fixed
dose combinations of aclidinium/formoterol 400/12mcg and 400/6mcg versus
aclidinium alone in change from baseline in FEV1 at 1 hour post-dose at week
24. The aclidinium/formoterol 400/12mcg and 400/6mcg achieved statistically
significant improvements compared with aclidinium 400mcg (108mL and 87mL,
respectively).

2. The second co-primary endpoint consisted of the comparison between the
fixed dose combinations of aclidinium/formoterol 400/12mcg and 400/6mcg versus
formoterol alone in change from baseline in morning pre-dose trough FEV1 at
week 24. The aclidinium/formoterol 400/12mcg demonstrated statistically
significant improvement versus formoterol 12mcg (45mL). Aclidinium/formoterol
400/6mcg did not demonstrate statistically significant improvement versus
formoterol 12mcg (26mL).

In this AUGMENT COPD study, the aclidinium/formoterol 400/12mcg and 400/6 mcg
also demonstrated superior efficacy in the secondary efficacy comparison for
each co-primary parameter as compared to placebo, achieving statistically
significant benefits 1-hour post-dose FEV1 (284mL and 263mL, respectively) and
in trough FEV1 (130mL and 111mL, respectively).

The positive results of the aclidinium/formoterol 400/12mcg combination in
this study are consistent with the statistically significant improvement in
lung function demonstrated by aclidinium/formoterol 400/12mcg in the
previously completed ACLIFORM/COPD Phase III study.

About the ACLIFORM/COPD Phase III Study

ACLIFORM/COPD (ACLIdinium/FORMoterol fumarate combination for Investigative
use in the treatment  of moderate to severe COPD) was a 24-week randomized
double-blind trial evaluating the 400/6mcg and 400/12mcg fixed dose
combinations of aclidinium bromide/formoterol fumarate compared with
aclidinium bromide 400mcg, formoterol fumarate 12mcg and placebo administered
BID through the Genuair^®/Pressair™ inhalers in 1729 patients with moderate to
severe COPD, in 22 countries including Europe, Korea and South Africa.

The full results of both studies will be presented at future scientific
meetings.

About Aclidinium/Formoterol

Aclidinium bromide /formoterol fumarate (400/12mcg and 400/6mcg) are
investigational fixed dose combinations of two approved long-acting
bronchodilators with different mechanisms of action and similar
pharmocodynamic profiles. Aclidinium bromide is an anticholinergic or
long-acting muscarinic antagonist (LAMA) that produces bronchodilation by
inhibiting the muscarinic M3 receptor in the airway smooth muscle. Formoterol
fumarate is a long-acting beta-agonist (LABA) that stimulates the B2-receptors
in the bronchial smooth muscle resulting in bronchodilation. Both aclidinium
bromide (Tudorza^®/Elkira^® and formoterol fumarate are approved for the
maintenance treatment of COPD in the United States and Europe.

Aclidinium/formoterol was administered using a multiple-dose dry powder
inhaler, Pressair® (outside of the United States the inhaler is marketed as
Genuair^®), which delivers 60 doses of aclidinium bromide/formoterol powder
for inhalation. The Pressair^® inhaler has a colored control window which
confirms successful inhalation of the full dose and a dose indicator to let
patients know approximately how many doses remain in the inhaler. The
Pressair^®/Genuair^® inhaler is approved in the United States and Europe for
the administration of Tudorza^®/Eklira^®.

Aclidinium/formoterol combines two effective bronchodilators with
complementary mechanisms of action and is being evaluated as a potential
treatment for COPD patients who could benefit from two bronchodilators
administered in a single multi-dose inhaler.

About COPD

Chronic Obstruction Pulmonary Disease (COPD), or chronic obstructive pulmonary
disease, is a common, progressive, and debilitating lung disease characterized
by persistent airflow limitation that makes it hard to breathe. The World
Health Organization (WHO) has described COPD as a global epidemic; an
estimated 64 million people have COPD worldwide. More than 3 million people
died of the condition in 2005, which is equal to 5% of all deaths globally
that year. Total deaths from COPD are projected to increase by more than 30%
in the next 10 years without interventions to cut risks, particularly exposure
to tobacco smoke. WHO predicts that COPD will become the third leading cause
of death worldwide by 2030. COPD is already the third leading cause of death
in the U.S.

In patients with COPD the airways in the lungs typically lose their
elasticity, produce excess mucus and become thick and inflamed, limiting the
passage of air. The most common symptoms of COPD are breathlessness (or a
"need for air"), abnormal sputum (a mix of saliva and mucus in the airway),
and chronic cough. As the condition worsens and breathlessness increases,
daily activities, such as walking up a short flight of stairs or carrying a
suitcase, can become very difficult. New therapies to treat this debilitating
disease may be of value.

About Almirall

Almirall is a pharmaceutical company committed to provide valuable medicines
from our own R&D, external partnerships, licenses and collaborations. In 2012,
Almirall invested over 23% of its sales in R&D. Through seeking innovative
medicines we aim to become a relevant player in respiratory and dermatology
diseases with also a strong interest in gastroenterology and pain. With more
than 3,000 employees in 22 countries, Almirall generated total revenues of 900
million in 2012.

The company was founded in 1943 and is headquartered in Barcelona, Spain. The
stock is traded in the Spanish stock exchange (ticker: ALM). For more
information please visit www.almirall.com

Tudorza^®, Eklira^®, Genuair^® and Pressair^® are registered trademarks of
Almirall S.A.

About Forest Laboratories

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.

Contact:

Forest Laboratories, Inc.
Frank J. Murdolo, 212-224-6714
Vice President - Investor Relations
media.relations@frx.com
or
Almirall:
Media information:
Ketchum
Bianca Daneshfar-Nia, +44 20 76113510
bianca.daneshfar-nia@ketchumpleon.com
or
Investor Relations enquiries:
Jordi Molina, +34 93 291 30 87
jordi.molina@almirall.com
 
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