- New data analysis presented at ERS 2011 supports the ability of roflumilast to shift COPD patients from the frequent to the more stable infrequent exacerbator state1
- Data support use of roflumilast to prevent exacerbations, which currently impose a substantial burden on patients and health-care systems worldwide2
Nycomed today announced new findings to show that Daxas® (roflumilast) helps to prevent exacerbations in COPD patients of the ‘frequent exacerbator’ phenotype.1 The data, presented at the 2011 European Respiratory Society (ERS) Annual Congress in Amsterdam, 24 – 28 September, have important implications for the management of COPD in this patient population, who are at increased risk of disease progression compared with those who have no or infrequent exacerbations.2 Frequent exacerbations are of concern to a significant group of COPD patients, despite access to available therapy. 3 They are distressing for patients and lead to poorer health status and faster disease progression, imposing a substantial burden on patients.2 Exacerbations also significantly impact the functional ability of COPD patients – patients with frequent exacerbations reduce the time they spend outdoors at a faster rate compared with those with infrequent exacerbations and are more likely to become housebound.4
Lead investigator Professor Jadwiga Wedzicha comments: “The results of our analysis are important because they show that the anti-inflammatory effects of roflumilast can help to reduce exacerbations in the ‘frequent exacerbator’ phenotype and this is clinically significant from both the patients’ and clinicians’ perspective. This ‘frequent exacerbator’ group show worse health status and faster disease progression than those who are ‘infrequent exacerbators’. Thus in this patient population, reducing exacerbations is a key treatment goal. We also need to be better at identifying these patients at risk by proactively asking patients about their exacerbation history, including previous worsening episodes treated with oral steroids and/or antibiotics or requiring admission to hospital.”
The data presented at ERS 2011 are from a post-hoc pooled analysis of two one-year studies of more than 1,500 roflumilast-treated patients with severe COPD, chronic bronchitis and a history of exacerbations.1* Among patients identified as frequent exacerbators, treatment with roflumilast over a year lowered the risk for those remaining in the frequent exacerbator state by 20% as compared to placebo (RR=0.799, p=0.0148).1 Among patients identified as infrequent exacerbators, treatment with roflumilast over a year lowered the risk of becoming a frequent exacerbator by 23% as compared to placebo (RR=0.768, p=0.0018).1 Thus this analysis shows that roflumilast offers COPD patients an improvement in their exacerbations status by shifting patients from the frequent to the more stable infrequent exacerbator state.1
Anders Ullman, Executive Vice President, Research and Development at Nycomed, comments: “These are important data, as they continue to reinforce the therapeutic value of roflumilast to reduce exacerbation frequency. COPD exacerbations are frightening and devastating to experience, and roflumilast provides added value to patients suffering from frequent exacerbations by helping them achieve a more stable disease state.”
Daxas is the first in a new class of treatment, phosphodiesterase 4 (PDE4) inhibitors, and has received approval in several countries, including the European Union, US and Canada for the treatment of severe COPD associated with chronic bronchitis. In the 2010 update of its COPD management guidelines, The Global Initiative for Chronic Obstructive Lung Disease (GOLD) included roflumilast as a new treatment option, acknowledging its principal action to reduce inflammation and the clinical implications in terms of exacerbation reduction in GOLD stage III and IV COPD patients.5
* Notes to editors
Among roflumilast-treated frequent exacerbators (n=413), 32.0% still had frequent exacerbations at year 1 vs. 40.8% of placebo-treated patients (n=417; RR=0.799, p=0.0148).1 Among infrequent exacerbators, 17.5% of roflumilast-treated patients (n=1124) had ≥2 exacerbations at year 1 vs. 22.9% of placebo-treated patients (n=1137; RR=0.768, p=0.0018).1
About Daxas® (roflumilast)
Daxas (roflumilast) is an orally administered selective phosphodiesterase 4 (PDE4) enzyme inhibitor, which has been shown to inhibit COPD related inflammation with a novel mode of action.6 Daxas, a once-a-day tablet, is the first drug in a new class of treatment for severe COPD associated with chronic bronchitis and the first oral anti-inflammatory treatment specifically developed for COPD patients.
Four large randomized placebo controlled trials have shown that roflumilast significantly reduces exacerbations and improves lung function when added to long acting bronchodilators.7,8
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) included roflumilast as a new treatment option in the 2010 update of its COPD management guidelines, acknowledging its principal action to reduce inflammation and the clinical implications in terms of exacerbation reduction in GOLD stage III and IV COPD patients.5
Daxas is generally well tolerated. In clinical COPD trials involving 12,000 patients, the most commonly reported adverse reactions were diarrhoea (5.9%), weight decreased (3.4%), nausea (2.9%), abdominal pain (1.9%) and headache (1.7%). The majority of these adverse reactions were mild or moderate. These adverse reactions mainly occurred within the first weeks of therapy and mostly resolved on continued treatment.9
Other pharmacological treatment for COPD patients includes the use of inhaled bronchodilators and inhaled corticosteroids.
COPD remains a significant area of unmet medical need. It is a progressive and irreversible lung disease resulting in difficulty in breathing. The disease is characterised by severe episodes of worsening, called exacerbations or lung attacks. According to World Health Organization (WHO) estimates, 80 million people have moderate to severe COPD worldwide. More than 3 million people died of COPD in 2005, which corresponds to 5% of all deaths globally. The WHO predicts that total deaths from COPD could increase by more than 30% in the next 10 years unless urgent action is taken to reduce the underlying risk factors, especially smoking. www.who.int/respiratory/copd/burden/en/index.html
Nycomed is a privately owned global pharmaceutical company with a diversified portfolio focused on branded medicines in gastroenterology, respiratory and inflammatory diseases, pain, osteoporosis and tissue management. A range of OTC products completes the portfolio.
Its R&D is structured around collaborations. In-licensing and expanding in emerging markets are cornerstones of the company's growth strategy.
Nycomed employs 12,500 associates worldwide, and its products are sold in more than 100 countries. It has strong platforms in Europe and in fast-growing markets such as Russia/CIS, Latin America, Asia and the Middle East. In the US and Japan its products are available through best in class partners.
Headquartered in Zurich, Switzerland, the company generated total sales of € 3.2 billion in 2010 and an adjusted EBITDA of € 851 million.
(1) Wedzicha JA et al. Efficacy of roflumilast in the frequent exacerbation COPD phenotype. Presented at 2011 European Respiratory Society Annual Meeting, Poster Discussion : Biomarkers and exacerbations of asthma and COPD, Tuesday 28 September 2011, 8:30-10:30, P3355.
(2) Wedzicha JA and Seemungal TAR. COPD exacerbations: defining their cause and prevention. Lancet 2007; 370: 786–96
(3) Hurst HR et al. Susceptibility to Exacerbation in Chronic Obstructive Pulmonary Disease N Engl J Med. 2010;363:1128- 38 .
(4) Donaldson GC, et al. Exacerbations and time spent outdoors in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005; 171:446-452.
(5) From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2010. Available from www.goldcopd.org/
(6) Hatzelmann A, et al. The preclinical pharmacology of roflumilast – a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease, Pulm Pharm Ther 2010;23:235–256.
(7) Calverley PMA, et al. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet 2009; 374: 685–94.
(8) Fabbri LM, et al. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials. Lancet 2009; 374: 695–703.
(9)EU Summary of Product Characteristics, Daxas®, May 2011