Almirall and Forest Announce Positive Results from the ATTAIN Phase III Study of Aclidinium Bromide and the Phase IIb Studies with the Fixed Dose Combination with Formoterol in Moderate to Severe COPD Patients

BARCELONA, Spain & NEW YORK--(BUSINESS WIRE)--Jan 4, 2011 - Almirall, S.A. (ALM.MC) and Forest Laboratories, Inc. (NYSE: FRX) today announced positive top-line results of ATTAIN, a six month double-blind placebo-controlled pivotal Phase III study comparing the efficacy and safety of inhaled aclidinium bromide 200μg and 400μg twice daily (BID) versus placebo, in 828 patients with moderate to severe COPD.

Aclidinium 200µg and 400µg produced statistically significant increases from baseline in morning pre-dose (trough) FEV1 versus placebo at week 24 (99mL and 128mL, respectively; p<0.0001), which was the primary endpoint of the study for Europe, and at week 12 (77mL and 105mL, respectively; p‰¤0.0001) which was the primary endpoint for the US.

All secondary endpoints demonstrated statistically significant differences vs placebo for both doses. These endpoints included peak FEV1, and the percentage of patients achieving a clinically meaningful reduction in breathlessness (assessed by a 1 unit improvement in Transition Dyspnea Index) and the percentage of patients with improved health status (assessed by a 4-unit improvement in the St. George's Respiratory Questionnaire).

Additionally, throughout the entire study, aclidinium produced statistically significant changes from baseline in trough FEV1 vs placebo at each time-point, which ranged from 77mL to 105mL for aclidinium 200µg and from 105mL to 140mL for aclidinium 400µg.

Aclidinium was well tolerated in this study. The incidence of adverse events and serious adverse events was similar across the three study treatment arms.

“We are very pleased with these results which demonstrate that aclidinium provided consistent bronchodilation and symptom control in COPD patients suffering from this debilitating disease”, said Jorge Gallardo, Chairman and Chief Executive Officer at Almirall. “With these results, we anticipate regulatory filings for aclidinium BID monotherapy this year”.

Regulatory submissions in Europe and the US for aclidinium bromide monotherapy are both planned for mid 2011.

Aclidinium and formoterol fixed dose combination Phase IIb Studies

Two Phase IIb dose-ranging studies comparing fixed-dose combinations (aclidinium bromide / formoterol) to aclidinium bromide alone, formoterol alone and placebo, administered BID in patients with stable moderate to severe COPD, have also been successfully completed. Both studies showed statistically significant (p<0.001) differences for the fixed dose combination on the primary endpoint versus placebo (normalized AUC 0-12 hours FEV1). The fixed dose combinations also provided improved bronchodilation compared to aclidinium alone and formoterol alone. Following regulatory consultations, Phase III with the fixed dose combination will commence in the second half of 2011.

"Together with our partner Almirall, we are delighted with the ATTAIN results which confirm the efficacy reported in the ACCORD COPD I study. We are also encouraged by the results achieved with the fixed dose combination of aclidinium and formoterol in the Phase IIb studies, a combination of two bronchodilators, each with a different mode of action. We believe that aclidinium, a proprietary long-acting inhaled muscarinic antagonist, and formoterol, a long-acting inhaled beta agonist may be a desired combination for the treatment of COPD,” said Howard Solomon Chairman and Chief Executive Officer of Forest Laboratories.

About ATTAIN Phase III study

ATTAIN (Aclidinium To Treat Airway obstruction In COPD patieNts) was conducted in Europe and South Africa. It was a 24 week study, which assessed the long term bronchodilator efficacy and safety of inhaled aclidinium bromide 200 μg and 400 μg, both administered BID, compared to placebo in 828 moderate to severe COPD patients (mean baseline FEV1= 1480mL). In addition, it assessed the benefits of aclidinium bromide 200μg and 400μg, compared to placebo, in disease-related health status and COPD symptoms.

Aclidinium 200µg and 400µg produced statistically significant increases from baseline in morning pre-dose (trough) FEV1 versus placebo at week 24 (99mL and 128mL, respectively; p<0.0001), which was the primary endpoint of the study for Europe, and at week 12 (77mL and 105mL, respectively; p‰¤0.0001) which was the primary endpoint for the US.

Aclidinium also demonstrated statistically significant improvement vs placebo on the three secondary endpoints assessed in the study:

 

  • Changes from baseline in peak FEV1 observed after morning dosing with 200μg or 400μg of aclidinium at weeks 12 and 24 (p<0.0001 for both doses at both time points).
  • Percentage of patients experiencing a clinically meaningful improvement of greater than or equal to 1-unit from baseline in shortness of breath at week 24, as measured by the Transition Dyspnea Index (TDI), (p=0.032 for aclidinium 200μg; p=0.004 for aclidinium 400μg).
  • Percentage of patients achieving a clinically meaningful improvement of greater than or equal to 4-units from baseline in health related quality of life, as measured by the St. George's Respiratory Questionnaire (SGRQ) at week 24 (p=0.0004 for aclidinium 200μg; p=0.0014 for aclidinium 400μg).

Additionally, throughout the entire study, aclidinium produced statistically significant changes from baseline in trough FEV1 vs placebo at each time-point, which ranged from 77mL to 105mL for aclidinium 200µg and from 105mL to 140mL for aclidinium 400µg.

Aclidinium was well tolerated in this study. The percentage of patients reporting adverse events and serious adverse events was similar in the placebo, 200μg and 400μg treatment arms. The most common adverse events (higher than 5% and reported more frequently with aclidinium than placebo) were headache and nasopharyngitis. Also, the incidence of anticholinergic adverse events was low and comparable to placebo (e.g. dry mouth and constipation were both <1%).

Endpoint Definitions

 

  • FEV1 - Forced expiratory volume in one second, or the amount of air that can be exhaled in the first second, following an inhalation.
  • Morning pre-dose (trough) FEV1 - average of two FEV1 measurements within 1 hour before morning treatment administration.
  • Normalized AUC (0-12 hours) FEV1 - Average area under the FEV1 curve over 12 hours, from dosing in the morning until pre-dose twelve hours later (0-12 hours).

About aclidinium bromide and the Genuair® inhaler

Aclidinium bromide is a novel, long-acting inhaled anticholinergic bronchodilator which has a long residence time at the M3 receptors and a shorter residence time at the M2 receptors. Aclidinium is rapidly hydrolyzed in human plasma to two major inactive metabolites. Forest Laboratories, Inc. licensed US rights for aclidinium from Almirall, while Almirall maintains rights for the rest of the world. The companies are jointly involved in the development of the compound.

Aclidinium bromide is administered to patients using a novel, investigational, state-of-the-art multidose dry powder inhaler (MDPI), Genuair®. The Genuair® inhaler was designed with a feedback system, which through a 'colored control window' and an audible click helps confirm that the patient has inhaled correctly. It contains multiple doses of aclidinium, includes a visible dose-level indicator and also incorporates safety features such as an anti-double-dosing mechanism and an end-of-dose lock-out system to prevent use of an empty inhaler. Genuair® is a registered trademark owned by Almirall, S.A.

About COPD

The World Health Organization (WHO) has described COPD as a global epidemic; an estimated 210 million people have COPD worldwide and 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.

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 a chronic cough. Daily activities, such as walking up a short flight of stairs or carrying a suitcase, can become very difficult as the condition gradually worsens. There are significant unmet needs in the treatment of COPD including limited therapeutic options to improve lung function, reduce symptoms and control exacerbations.

About Almirall

Almirall is an international pharmaceutical company based on innovation and committed to health. Headquartered in Barcelona, Spain, it researches, develops, manufactures and commercializes its own R&D and licensed drugs with the aim of improving people's health and wellbeing.

Almirall focuses its research resources on therapeutic areas related to the treatment of asthma, COPD (Chronic Obstructive Pulmonary Disease), rheumatoid arthritis, multiple sclerosis, psoriasis and other dermatological conditions.

Almirall's products are currently present in over 70 countries while it has direct presence in Europe and Latin America through 12 affiliates.

For further information please visit the website at: www.almirall.com

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 medicine. The Company'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.

 

Contact: Almirall
Media:
Ketchum Pleon
Annabel Gillett, +44 (0) 207.611.3559
annabel.gillett@ketchumpleon.com
Investors and Analysts:
Jordi Molina, +34 93 291 3087
Investor Relations
jordi.molina@almirall.com
or
Forest Laboratories, Inc
Frank J. Murdolo, +1-212-224-6714
Vice President - Investor Relations
Frank.Murdolo@frx.com

 

 

Posted: January 2011

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