New Data Show Seretide(reg) Achieves Disease Control in Asthma and COPD

Main Category: Respiratory / Asthma
Also Included In: COPD
Article Date: 27 May 2004 - 5:00 PST


GlaxoSmithKline [GSK] today announced new data supporting SeretideTM (salmeterol / fluticasone propionate) in the maintenance of COPD have been released at the 100th annual meeting of the American Thoracic Society in Orlando.

This new evidence follows the approval of Seretide in the European Union last May and its launch in the US in January 2004 for the treatment of Chronic Obstructive Pulmonary Disease (COPD). Findings from the COPD study show an increase in patient symptoms on discontinuation of Seretide.

These findings are complemented by new results from asthma studies, which revealed a loss of asthma control when Seretide was discontinued, showing that maintenance treatment with Seretide provides greater disease control than treatment with the individual components alone.

Findings from the COPD study COSMIC1, conducted in 373 patients, show that there is a key role for the inhaled corticosteroid fluticasone propionate (FP), in combination with established long acting beta2-agonist (LABA), salmeterol (S) as Seretide in maintaining stable COPD.

The trial examined the response of patients with COPD to Seretide and to the subsequent withdrawal of FP. Results* showed that patients experienced an immediate change in their health status with the withdrawal of FP, including:

- increased shortness of breath within 2 days

- a sustained decrease in FEV1

- an increase in disturbed night sleeps

- an increase in mild exacerbations

These results indicate that the addition of FP to salmeterol as Seretide is more effective than salmeterol in maintaining control of symptoms, improving lung function and delaying exacerbations, giving patients important treatment benefits compared with LABA alone and providing further support for combination therapy as the optimal treatment for COPD.

"These new data provide a strong case for the use of salmeterol / fluticasone propionate combination in COPD. The data clearly demonstrate the contribution fluticasone propionate has in maintaining disease stability, as well as reducing distressing symptoms such as breathlessness and night-time waking," said Professor EM Wouters, of University Hospital Maastricht in the Netherlands.

"The inclusion of an inhaled corticosteroid appears to prevent an otherwise rapid and persistent deterioration of the disease."

In asthma, two new trials** also presented at the ATS show that once asthma control is established with Seretide (50/100 mcg bd.), changing treatment to FP (100 mcg bd.), salmeterol (50 mcg bd.) or montelukast (10 mg once daily) can result in loss of asthma control. For example, significant deterioration in morning peak flow was observed when other treatments were substituted for Seretide, in these two studies, which examined response to a change in treatment for 1288 patients whose asthma had been stable on Seretide. Patients not on Seretide also required more rescue treatment during the trial period, whereas Seretide patients reduced their need of rescue treatment. 2, 3.

Dr Paul Dorinsky, Senior Director Clinical Development Medical Affairs, RTP, said: "This study confirms that by treating the two components of asthma, airway inflammation and smooth muscle dysfunction (including bronchoconstriction), a high level of asthma control is achieved. The study also demonstrates the need to maintain treatment of the two main components of asthma to maximise benefits for many patients, irrespective of their baseline asthma severity."

It is estimated that around 300 million people in the world currently have asthma, according to the GINA Global Burden of Asthma Report.4 In Western Europe, asthma prevalence has doubled in the last 10 years and worldwide deaths from the condition have reached over 180,000 annually.5 It is also estimated that an additional 100 to 150 million persons are likely to have asthma by 2025.4 COPD prevalence is even greater with an estimated 600 million COPD sufferers world-wide.6 Significantly, COPD is the only leading global cause of death that is increasing. Coronary heart disease, other cardiovascular disease and stroke all show consistent and substantial reductions by contrast.7 COPD places an enormous burden on Europe's healthcare system. The total of COPD-related expenses for outpatient care in Europe is E4.7 billion and inpatient care generates costs of E2.9 billion.8

Breakthrough data are expected in both asthma and COPD in the near future. In asthma, the GOAL (Gaining Optimal Asthma controL) trial will be the first prospective international trial to test whether total control of asthma symptoms is achievable. GOAL uses a stringent definition of total control, normal lung function, no symptoms, no night-time awakenings, no rescue medication, no exacerbations, no emergency visits and no adverse effects of the drug - and subjects must maintain this level of control for seven out of eight consecutive weeks to be classified as having 'Total Control.'

This year-long study is expected to redefine the current approach to asthma management.9.

In COPD, TORCH (TOwards a Revolution in COPD Health) will be the first and largest prospective study designed to investigate the effects of Seretide 50/500mcg bd. on mortality in COPD. The study is being conducted in over 6000 patients worldwide and will determine whether Seretide (50/500) has an effect on survival in COPD patients treated over three years. The results are expected around 2006.10.

GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

- ends -

Notes to editors:

*COSMIC Study - The study recruited from 39 centres in the Netherlands, and tested the response of 373 COPD patients, who were treated with an S/FP combination (Seretide 500/50 bd. via Diskus(reg) Inhaler) for three months, to the withdrawal of FP. Their response to subsequent treatment with salmeterol alone was assessed over the following 12 months, through measurements of daily symptoms such as breathlessness, percentage of disturbed nights, sputum production, cough and clinical measures such as FEV1 and percentage of rescue medication free days.

Results from the COSMIC study showed that patients experienced an immediate and dramatic change in their health status with the withdrawal of FP.1

- shortness of breath within 2 days (scale 0-4; mean difference 0.17 (0.04), p<0.001)

- a sustained decrease in FEV1, (FEV1, was clearly linked to the occurrence of the first exacerbation)

- an increase in disturbed night sleeps (mean difference 6% P<0.001)

- an increase in mild exacerbations (1.3 (salmeterol) vs. 0.6 salmeterol/fluticasone propionate, p=0.020)

In terms of exacerbations, the results showed that the rates for women were higher than the rates for men (by a factor of 1.4). Furthermore, over the subsequent 12 months patients experienced a decrease in rescuemedication free days (when symptoms were too severe to manage without additional medication) from 53 (2) % (salmeterol/fluticasone), vs. 47 (2) salmeterol vs. p=0.014).

**Patients involved in these two studies completed a two week run-in on inhaled steroids alone and then switched to Seretide (50/100 mcg) twice daily for four weeks. At this point, patients (n=1288) were randomly stepped down to either fluticasone propionate, salmeterol or montelukast for 16 weeks treatment.

Please note: The treatment of asthma with salmeterol alone is not recommended by GSK. Please refer to local guidelines.

Seretide/Advair in COPD

In the European Union, SeretideTM is indicated for the symptomatic treatment of patients with severe COPD (FEV1 50% predicted normal) and a history of repeated exacerbations, who have significant symptoms despite regular bronchodilator therapy.

SeretideTM/Advair(reg) in COPD is also approved in over 60 countries worldwide.

Seretide/Advair in Asthma

Salmeterol / fluticasone propionate combination is marketed as SeretideTM DiskusTM in most European countries and as SeretideTM AccuhalerTM in the United Kingdom and is indicated for the treatment of asthma in adults and children (over the age of four years) for whom treatment with both inhaled corticosteroid and a long-acting beta2- agonist is appropriate.

References:

1. Wouters EFM et al. One year withdrawal of fluticasone after three months treatment with combined salmeterol/fluticasone in COPD: results of the COSMIC study. Presented at American Thoracic Society

Annual Conference 2004; poster ref 515 May 25 2004

2. Dorinsky P,Stauffer J, Waitkus-Edwards K. Stepping down from Fluticasone/salmeterol combination Diskus results in loss of control-irrespective of baseline, Presented at American Thoracic Society Annual Conference 2004;poster A37;May 23rd 2005

3. Oppenheimer J, Stauffer J, Waitkus-Edwards K. Stepping down from Fluticasone/salmeterol combination Diskus, Presented at American Thoracic Society Annual Conference 2004;poster A37;May 23rd 2005

4. Masoli M, Fabian D, Holt S and Beasley R. Global Burden of Asthma. Published by the Global Initiative for Asthma (GINA)

5. Bronchial Asthma. World Health Organisation Fact Sheet No. 206. Revised January 2000

6. The World Health Report 1998. Life in the 21st Century. A vision for all. World Health Organisation, Geneva, 1998

7. National Heart, Lung and Blood Institute. Morbidity and mortality: chartbook on cardiovascular, lung and blood diseases. Bethesda, MD: US Department of Health and Human Services, Public Health Service, National Institutes of Health; 1998. http://www.nhlbi.nih.gov/resources/docs/cht-book.htm (last accessed 15 April 2003)

8. European Lung White Book - The First Comprehensive Survey on Respiratory Health in Europe. European Respiratory Society and the European Lung Foundation, 2003. Pp41

9. Clark TJ, Bousquet J, Bateman ED, James MH. GOAL (gaining optimal asthma control): a study to assess asthma control. Eur Respir J 2001; 18 (Suppl 33): 175-176s

10. Calverley PMA et al Eur Respir J 2003; 22(Suppl 45): 578s

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