Eklira®/Bretaris® Genuair® (aclidinium bromide) Approved in Europe for the Maintenance Treatment of Chronic Obstructive

  Eklira®/Bretaris® Genuair® (aclidinium bromide) Approved in Europe for the
    Maintenance Treatment of Chronic Obstructive Pulmonary Disease (COPD)

  PR Newswire

  BARCELONA, Spain, July 24, 2012

BARCELONA, Spain, July 24, 2012 /PRNewswire/ --

  *Aclidinium provides significant and sustained bronchodilation from the
    first dose. It also improves symptoms control and patients' quality of
    life ^[1]
  *COPD is a debilitating disease which is one of the most common causes of
    death in Europe. Patients suffer from difficulties to breathe, limitations
    in activities, poor quality of life and chronic cough and sputum
  *Aclidinium is a long acting muscarinic antagonist (LAMA) developed by
    Almirall's R&D. F irst launches are planned in Europe later this year

Almirall S.A. (ALM) announced today that the European Commission has granted
marketing approval to Eklira/Bretaris Genuair ^® (aclidinium 322µg twice
daily) in all EU member states, plus Iceland and Norway, as a maintenance
bronchodilator treatment to relieve symptoms in adult patients with Chronic
Obstructive Pulmonary Disease (COPD), following the positive recommendation
received from the CHMP in May this year.

" Patients with COPD have a high symptom burden, which can have important
effects on their quality of life " , commented Professor Paul W Jones, from St
George's Hospital, University of London, and principal investigator of the
ATTAIN phase III study. " The European approval of aclidinium is good news for
the healthcare community because improvements observed in health status and
symptoms within the trials can finally be translated into benefits for
patients in every-day practice " , he added.

Clinical efficacy studies showed that aclidinium provides around the clock
significant and sustained bronchodilation and symptoms control from the first
dose. These benefits were evident within 30 minutes of the first dose. It also
reduced moderate and severe exacerbations by approximately 30%. Patients
treated with aclidinium needed less rescue medication than patients treated
with placebo (p=0.005). It also improved COPD symptoms such as dyspnoea, cough
and sputum production. ^[1]

In addition the studies demonstrated that aclidinium provided clinically
meaningful improvements in breathlessness (assessed using the Transition
Dyspnoea Index [TDI] ^[ ^2] ) and disease-specific health status (assessed
using the St. George's Respiratory Questionnaire [SGRQ]) ^[3] .

" Almirall and its European partner Menarini are pleased with the approval of
Eklira/Bretaris Genuair ^® , an important milestone in Almirall ' s
respiratory franchise, one of our key R&D areas " said Eduardo Sanchiz, Chief
Executive Officer, Almirall. " We are convinced from our large set of
scientific data that aclidinium will help patients in  Europe  to reduce
COPD symptoms and improve their quality of life " .

Aclidinium showed a good safety profile, with the most frequently reported
adverse reactions being headache (6.6%) and nasopharyngitis (5.5%).
Importantly, the incidence of typical anticholinergic adverse events was low
and comparable to placebo (e.g. dry mouth and constipation were both <1%).
^[1]

Menarini will have joint commercialisation rights across the majority of EU
member states (excluding the UK, the Netherlands and the Nordic countries
where Almirall retains sole marketing rights for the product) as well as
Russia, Turkey and other CIS countries under the brand name Bretaris ^®
Genuair ^® , whilst Almirall will market the product in Europe as Eklira ^®
Genuair ^® .

Aclidinium is being developed worldwide and has been recently approved in the
USA by the FDA where it will be marketed by Forest Laboratories and marketed
under the name of Tudorza™ Pressair™. In Japan the product is in development
in partnership with Kyorin and with Daewoong in Korea. Almirall holds the
rights for the rest of the world.

Scientific evidence

The aclidinium Phase III clinical development programme included 269 patients
treated with aclidinium 322 µg twice daily in one 6-month randomised,
placebo-controlled study and 190 patients treated with aclidinium 322 µg twice
daily in one 3-month randomised, placebo-controlled study. Efficacy was
assessed by measures of lung function and symptomatic outcomes such as
breathlessness, disease-specific health status, use of rescue medication and
occurrence of exacerbations. In the long-term safety studies, Aclidinium was
associated with bronchodilatory efficacy when administered over a 1-year
treatment period.

Bronchodilation

In the 6 month study, patients receiving Aclidinium 322 µg twice daily
experienced a clinically meaningful improvement in their lung function (as
measured by FEV1). Significant bronchodilatory effects were evident from day
one and were maintained over the 6-month treatment period. After 6 months
treatment, the mean improvement in morning pre-dose (trough) FEV1 compared to
placebo was 128 mL (95% CI=85 170; p<0.0001). Similar observations were made
with Aclidinium in the 3 month study.

Disease-Specific Health Status and Symptomatic Benefits

Aclidinium provided clinically meaningful improvements in breathlessness
(assessed using the Transition Dyspnoea Index [TDI]): mean changes vs baseline
=1 unit (p<0.001) and disease-specific health status (assessed using the St.
George's Respiratory Questionnaire [SGRQ]): mean change vs baseline -4.6 units
(p<0.0001).

Patients treated with aclidinium required less rescue medication than patients
treated with placebo (a reduction of 0.95 puffs per day at 6 months
[p=0.005]). Aclidinium also improved daily symptoms of COPD (dyspnoea, cough
and sputum production) and night-time and early morning symptoms.

Reduction in the rate of Moderate to Severe Exacerbations

Pooled efficacy analysis of the 6-month and 3-month placebo controlled studies
demonstrated a statistically significant reduction in the rate of moderate to
severe exacerbations (requiring treatment with antibiotics or corticosteroids
or resulting in hospitalisations) with aclidinium 322 µg twice daily compared
to placebo (rate per patient per year: 0.31 vs 0.44 respectively; p=0.0149).

Absorption

Aclidinium bromide is rapidly absorbed from the lung, achieving maximum plasma
concentrations within 5 minutes of inhalation in healthy subjects, and
normally within the first 15 minutes in COPD patients. The fraction of the
inhaled dose that reaches the systemic circulation as unchanged aclidinium is
very low at less than 5%.

About the Genuair ^®  inhaler

Aclidinium is administered to patients using the novel multidose dry powder
inhaler (MDPI), Genuair ^® . The inhaler comes loaded and assembled and ready
for immediate use. Almirall's inhaler was designed with a "click and colour"
feedback system which, through a 'colour control window' and an 'audible
click', indicates that the patient has inhaled the dose correctly. It also
incorporates significant safety features such as a visible dose indicator, an
anti-double-dosing mechanism and an end-of-dose lock-out system to prevent use
of an empty inhaler.

About COPD

COPD is the occurrence of chronic bronchitis or emphysema, a pair of commonly
co-existing diseases of the lungs in which the airways become narrowed. This
leads to a limitation of the flow of air to and from the lungs, causing
shortness of breath (dyspnoea). In clinical practice, COPD is defined by its
characteristically low airflow on lung function tests.

The most common symptoms of COPD are breathlessness (an increased effort to
breathe), heaviness or a 'need for air', excessive mucus, and a chronic cough.
Some people feel they are gasping for breath. These symptoms get worse when
exercising, in case of a respiratory infection or during an exacerbation -
periods of time when there is a sudden increase in symptoms and the disease is
worse. COPD affects the ability to breathe and is a progressive disease, which
means that COPD gets worse over time. Daily activities may become more
difficult as the disease worsens. There are significant unmet needs in the
treatment of COPD and new therapies may be of value.

The World Health Organization (WHO) has described COPD as a global epidemic,
and it is estimated that 210 million people suffer COPD worldwide.

In the European Union, the total direct costs of respiratory diseases are
estimated to be approximately 6% of the total healthcare budget, with COPD
accounting for more than half (56%) of this expenditure, equating to €38.6
billion ^[4] . Approximately 200,000-300,000 people die each year in Europe
because of COPD ^4 . Patients experiencing frequent exacerbations are at risk
of increased morbidity and mortality, a faster decline in lung function, and
poorer health status.

In the EU, approximately 41.3% lost work days are due to COPD every year and
productivity losses due to COPD amount to a total of €28.5 billion annually.

About Almirall

Almirall is an international pharmaceutical company based on innovation and
committed to health. Headquartered in Barcelona, it researches, develops,
manufactures and commercialises its own R&D and licensed drugs with the aim of
improving people's health and wellbeing. Almirall focuses its research
resources on respiratory, gastrointestinal, dermatology and pain. Almirall's
products are currently present in over 70 countries in the five continents. It
has direct presence in Europe and Mexico through 12 affiliates.

Almirall's respiratory franchise is complemented by aclidinium combination
products for COPD, currently in late stage development and abediterol (a once
daily LABA combined with an ICS) for asthma and COPD, currently under
development, set to move into Phase IIb development worldwide (excluding USA).

For further information please visit: http://www.almirall.com

References

1. Efficacy and safety of twice-daily aclidinium bromide in COPD patients: The
ATTAIN study - Paul W. Jones, et al - Eur Respir J 02255-2011; published ahead
of print 2012, doi:10.1183/09031936.00225511

and

Efficacy and Safety of a 12-week Treatment with Twice-daily Aclidinium Bromide
in COPD Patients (ACCORD COPD I) Edward M. Kerwin, et al - COPD: Journal of
Chronic Obstructive Pulmonary Disease April 2012, Vol. 9, No. 2, Pages 90-101:
90-101

2. Witek TJ. Minimum clinically important difference (MCID) of at least 1 unit
change in TDI vs placebo - Minimal important difference of the transition
dyspnoea index in a multinational clinical trial. European Respiratory
Journal. 2003;21(2):267-72.

3. Jones PW. Minimum clinically important difference (MCID) of at least - 4
units change in St. George's Respiratory Questionnaire SGRQ - COPD. Journal of
Chronic Obstructive Pulmonary Disease. 2005; 2(1)75-79.

4. Global Initiative for Chronic Obstructive Lung Disease 2011

Contact: Media enquiries: Bianca Daneshfar-Nia, +44-20-7611-3510,
bianca.daneshfar-nia@ketchumpleon.com
 
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