FDA approves Forest Labs' Daliresp to treat COPD

Forest Laboratories, Inc. (NYSE: FRX) announced today that Daliresp^TM (roflumilast) was approved by the U.S. Food and Drug Administration (FDA) as a treatment to reduce the risk of chronic obstructive pulmonary disease (COPD) exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. The efficacy and safety of Daliresp was evaluated in eight clinical studies including 9,394 adult patients.

COPD is an under-diagnosed, progressive, irreversible lung disease. Symptoms of COPD include breathlessness, chronic cough and excessive production of phlegm. A significant worsening of symptoms - called an exacerbation - can last several weeks and often requires substantial medical intervention, including hospitalization.

Daliresp is the first and only selective phosphodiesterase-4 (PDE4) inhibitor approved and is an oral tablet taken once daily. While the specific mechanism by which Daliresp exerts its therapeutic action in COPD patients is not well defined, it is thought to be related to the effects of increased intracellular cyclic AMP in lung cells. Forest expects Daliresp to be available to wholesalers in the second calendar quarter of 2011.

"We are pleased with the FDA approval of Daliresp and we are looking forward to making this treatment available in the United States for the millions of patients suffering from severe COPD," commented Howard Solomon, Chairman, Chief Executive Officer and President of Forest Laboratories. "The approval of Daliresp gives physicians and patients a much needed treatment option in a unique oral dosage form that can augment the existing armamentarium of inhaled therapies."

"The introduction of Daliresp as an additional treatment option to reduce the risk of COPD exacerbations is an important development for patients with severe COPD associated with chronic bronchitis and a history of exacerbations," said Professor Stephen Rennard, M.D., University of Nebraska Medical Center and clinical trial investigator. "Reducing the risk of COPD exacerbations is an important goal of COPD treatment."

Data Highlights

The efficacy and safety of Daliresp was evaluated in eight randomized double-blind, controlled, parallel group clinical trials involving 9,394 adult patients, of which 4,425 were treated with Daliresp 500 mcg.

1-Year Exacerbation Trials Supporting Approval

Of the eight trials, two 1-year trials supported approval and enrolled patients with severe COPD associated with chronic bronchitis, at least one COPD exacerbation in the previous year, and at least a 20 pack-year smoking history. In these trials, long-acting beta-agonists and short-acting anti-muscarinics were used by 44% and 35% of patients treated with Daliresp and 45% and 37% of patients treated with placebo, respectively. The rate of exacerbations (moderate or severe) was one of the co-primary endpoints. Moderate exacerbations were defined as requiring intervention with systemic glucocorticosteroids and severe exacerbations were defined as leading to hospitalization and/or to death. One of these trials randomized a total of 1525 patients (765 on Daliresp) and the other randomized a total of 1571 patients (772 on Daliresp). In both trials, Daliresp 500 mcg once daily demonstrated a significant reduction in the rate of moderate or severe exacerbations compared to placebo. Daliresp reduced the rate of moderate or severe exacerbations by 15% in one trial and by 18% in the other trial.

These trials also evaluated the effect of Daliresp on lung function as the other co-primary endpoint. Daliresp is not a bronchodilator and is not indicated for the relief of acute bronchospasm.

Summary of All Studies

Of the eight trials, two were placebo-controlled dose selection trials, four were placebo-controlled 1-year trials primarily designed to evaluate the efficacy of Daliresp on COPD exacerbations, and two were 6-month trials with Daliresp as add-on therapy to a long-acting beta-agonist or long-acting anti-muscarinic which provide safety support for the Daliresp COPD program. The initial two 1-year trials identified the patient population that could benefit from Daliresp; FDA approval of Daliresp was based on the results from the two subsequent 1-year exacerbation trials that are described above.

Safety

The most common adverse reactions, occurring in less than or equal to 10% of patients receiving Daliresp in the eight trials, included diarrhea, weight decrease, nausea, headache, back pain, influenza, insomnia, dizziness, and decreased appetite.