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

Almirall and Forest Laboratories 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 in the United States Food and Drug
        Administration (FDA) and European Medicines Agency (EMA) are
        planned in Q4 2013

BARCELONA and NEW YORK, May 2, 2013 /CNW/ - Almirall, S.A. (ALM:MC) and Forest 
Laboratories, Inc. (NYSE:FRX) 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) for the treatment of 
Chronic Obstructive Pulmonary Disease (COPD), delivered in the 
Pressair™inhaler (Genuair(®) outside the USA).

The 400/12mcg combination of aclidinium/formoterol given twice daily 
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 endpoints. The endpoints analyzed to date were 
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 SGRQ 
in 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%).

"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 marks an important milestone towards 
achieving an innovative global respiratory franchise around aclidinium and the 
Almirall's Genuair inhaler."

"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."

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 1,692 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 400/6mcg 
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 1,729 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.

Aboutaclidinium/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 Pulminary 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 its 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 around 
3,000 employees in 22 countries, Almirall generated total revenues of 900 
million Euros 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 http://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 http://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 Almirall: Media information: Ketchum, Simon 
Perry,simon.perry@ketchumpleon.com, Tel.: +44-20-76113562 ; Investor 
Relations enquiries: Almirall, Jordi  Molina,jordi.molina@almirall.com , 
Tel.: +34-93-291-30-87 ; Contact Forest: Forest Laboratories, Inc.,  Frank J. 
Murdolo, +1-212-224-6714, Vice President - Investor Relations, 
media.relations@frx.com

SOURCE: Almirall, S.A. and Forest Laboratories, Inc.

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CO: Almirall, S.A. and Forest Laboratories, Inc.
ST: New York
NI: MTC 

-0- May/02/2013 08:13 GMT


 
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