Home » Drug Information » FDA Approved Drugs » 2011
Medical Areas: Immunology | Pediatrics/Neonatology | Pulmonary/Respiratory Diseases | Family Medicine
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The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Company: Forest Pharmaceuticals
Approval Status: Approved February 2011
Treatment Area: chronic obstructive pulmonary disease
Daliresp (roflumilast) is a selective phosphodiesterase 4 (PDE4) inhibitor. Inhibition of PDE4 activity reduces the release of inflammation mediators and can counteract damage to tissue, allowing respiratory muscles to relax and therefore potentially improving lung function.
Daliresp is specifically indicated as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations.
Daliresp is supplied as a tablet for oral administration. The recommended initial dose is is one 500 microgram (mcg) tablet per day, with or without food.
The FDA approval of Daliresp was based on eight randomized double-blind, controlled, parallel group clinical trials in 9,394 adults. Of the eight trials, two were placebo-controlled dose selection trials (Trials 1 and 2) of 6 months duration that evaluated the efficacy of Daliresp 250 mcg and 500 mcg once daily, four were placebo-controlled 1-year trials (Trials 3, 4, 5, and 6) primarily designed to evaluate the efficacy of Daliresp on COPD exacerbations, and two were 6-month efficacy trials (Trials 7 and 8) which assessed the effect of Daliresp (250 mcg and 500 mcg once daily) as add-on therapy to a long-acting beta agonist or long-acting anti-muscarinic. COPD exacerbations and lung function (FEV1) were co-primary efficacy outcome measures in the four 1-year trials. Lung function (FEV1) alone was the primary efficacy outcome measure In the two 6-month supportive efficacy trials.
Effect on Exacerbations
Trials 3 and 4 failed to demonstrate a significant reduction in the rate of COPD exacerbations. Exploratory analyses of the results of Trials 3 and 4 identified a subpopulation of patients with severe COPD associated with chronic bronchitis and COPD exacerbations within the previous year that appeared to demonstrate a better response in the reduction of the rate of COPD exacerbations compared to the overall population. As a result, two subsequent trials (Trial 5 and Trial 6) were conducted that enrolled patients with severe COPD but 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 allowed. In both trials, Daliresp 500 mcg once daily demonstrated a significant reduction in the rate of moderate or severe exacerbations compared to placebo.
Effect on Lung Function
In Trials 3, 4, 5 and 6 Daliresp 500 mcg once daily demonstrated a statistically significant improvement in FEV1 which averaged approximately 50 mL across the four trials.
Adverse effects associated with the use of Daliresp may include, but are not limited to, the following:
- weight decrease
- back pain
- decreased appetite
Mechanism of Action
Daliresp (roflumilast) is a selective phosphodiesterase 4 (PDE4) inhibitor. Inhibition of PDE4 activity leads to accumulation of intracellular cyclic AMP. While the specific mechanism(s) 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.
Fabbri LM, Calverley PM, Izquierdo-Alonso JL, Bundschuh DS, Brose M, Martinez FJ, Rabe KF; M2-127 and M2-128 study groups Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials. Labcet 2009 Aug 29;374(9691):695-703
Calverley PM, Rabe KF, Goehring UM, Kristiansen S, Fabbri LM, Martinez FJ; M2-124 and M2-125 study groups Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet 2009 Aug 29;374(9691):685-94
Calverley PM, Sanchez-Toril F, McIvor A, Teichmann P, Bredenbroeker D, Fabbri LM Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease. Americam Journal of Respiratory and Critical Care Medicine 007 Jul 15;176(2):154-61.
For additional information regarding Daliresp or COPD, please visit the Daliresp web page.