The European Commission granted Nycomed marketing authorization for Daxas® (roflumilast). The drug is indicated as an add-on to bronchodilator therapy for maintenance treatment of severe COPD (FEV1 post-bronchodilator less than 50% predicted) associated with chronic bronchitis in adult patients with a history of frequent exacerbations.
Daxas reportedly represents the first new class of treatment for COPD in more than a decade. It is a selective phosphodiesterase 4 (PDE4) enzyme inhibitor. It is taken as an oral tablet once a day and is expected to be launched in European countries, starting with Germany and the U.K.
On April 26, Nycomed and Merck & Co. signed an agreement to co-promote Daxas in France, Germany, Italy, Spain, Portugal, and Canada. Nycomed will manufacture and distribute the finished product in all these countries. In addition, the two companies entered into an exclusive distribution arrangement for the commercialization of Daxas in the U.K. Nycomed will supply finished product and has retained a co-promotion option. For the U.S. the company signed a collaboration and distribution agreement with Forest Laboratories in August 2009. The NDA for Daxas was submitted in July 2009.
“Daxas is a novel therapy that improves lung function and most importantly reduces exacerbations,” says Klaus F. Rabe, M.D., lead author on various Daxas clinical trials from the University Medical Centre in Leiden, The Netherlands. “It has a unique mode of action that targets the underlying inflammation in COPD and is an important addition to the current options available to doctors and patients.”
Neil Barnes, M.D., professor of respiratory medicine at Barts and the London Hospital and Nycomed consultant, notes, “We have a large number of patients who remain symptomatic and have frequent exacerbations despite existing treatments, and for that more severe end of the spectrum we need new therapeutic options. The main additional benefit of Daxas on top of what is already achieved with bronchodilators is to reduce the number of exacerbations, or flare ups.”
The application to the EMEA was based on four Phase III trials in symptomatic COPD patients. In two placebo-controlled, 12-month studies involving over 3,000 patients, Daxas demonstrated statistically significant improvements on both co-primary endpoints: moderate-to-severe exacerbations and prebronchodilator FEV1.
The effect of Daxas was independent of concomitant use of long-acting beta2-agonist, according to Nycomed. In two supportive studies the drug also showed a statistically significant improvement compared to placebo on lung function over a six-month period when added to the bronchodilators tiotropium or salmeterol. Full data from all four studies was published in The Lancet in August 2009.