BARCELONA and NEW YORK, May 2,
2013 /PRNewswire/ --
- 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
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):
- 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).
- 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.
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 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.