UK Patients Set To Benefit As Seretide 500 Accuhaler Awarded Licence For Earlier COPD Use

Main Category: COPD
Also Included In: Pharma Industry / Biotech Industry
Article Date: 06 Sep 2007 - 2:00 PST

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Seretide™ 50/500µg (salmeterol/fluticasone propionate) has become the first combination treatment that can be prescribed to less severely ill patients with the lung disease COPD, thought to affect around three million people in the UK.1 The move follows a regulatory review of the TORCH (TOwards a Revolution in COPD Health) study by the MHRA.

"This is a major step forward for patients" commented Dr Steve Holmes, a GP in Somerset. "The licence extension means that healthcare professionals can now use Seretide earlier in the disease's progression, allowing more moderately ill patients to benefit from improvements in quality of life and lung function."

Seretide 500 Accuhaler is now indicated for the symptomatic treatment of patients with COPD with a FEV1 <60% predicted normal (pre-bronchodilator) and a history of repeated exacerbations, who have significant symptoms despite regular bronchodilator therapy.2 Forced expiratory volume in one second (FEV1), is a way of measuring the lung function of patients with COPD. A higher percentage indicates better lung function.

Prior to the label update, it was only when a patient's lung function had deteriorated to an FEV1 of <50% predicted, that Seretide 500 Accuhaler was indicated for use. This new indication means that more COPD patients may be able to use Seretide earlier in the course of the disease and benefit from improvements in quality of life and in lung function, before they reach the more severe stage of the disease. This update means that a broader range of COPD patients may benefit from this type of treatment with this type of combination therapy.

The three year TORCH study showed a relative risk reduction in mortality of 17.5% (p=0.052) with Seretide 500 Accuhaler vs control, which was just outside the predetermined level of statistical significance of p≤0.05. TORCH also showed that, versus control, Seretide improved health-related quality of life (HRQoL) (p<0.001)3, improved FEV1 (p<0.001)3 and reduced the rate of exacerbations by 25% (p<0.001)3.

The TORCH trial demonstrated an increase in traumatic fractures (statistically non-significant vs control), an increase in upper respiratory tract infections (statistically non-significant vs control), as well as an increased risk of lower respiratory tract infections (statistically non-significant vs control), including pneumonia (statistically significant vs control p<0.001).

The typical COPD patient experiences a decline in health status over time.4,5 Patients receiving Seretide in the TORCH study showed an improvement in their health status over the three years and at the end of the study remained above the baseline that they started from at the beginning of the study.3

About COPD

Chronic Obstructive Pulmonary Disease (COPD) is a debilitating and potentially fatal disease, but it can be both prevented and treated. The disease has a number of different components causing limitations to airflow in the lungs and breathing difficulties. These include increased inflammation in the airways, direct damage and structural changes to the lungs and reduced body mass, weakness and wasting, which affect the health status of the person and ultimately their survival. Improving survival remains a major unmet need for patients with COPD.3

More than three million people in the UK are thought to be affected by COPD1. Unfortunately, the disease takes around 30,000 lives in the UK each year6. By 2020 COPD is projected to be the third leading cause of death and fifth leading cause of disability worldwide following only ischaemic heart disease, depression, traffic accidents and cerebrovascular disease7.

About TORCH

TORCH (TOwards a Revolution in COPD Health) is the first and largest study to prospectively investigate the potential for Seretide (salmeterol/fluticasone propionate, SFC) 50/500 µg to impact survival in patients with Chronic Obstructive Pulmonary Disease (COPD). TORCH is a three year, multicentre, randomised, double-blind, parallel group placebo controlled study. Approximately 6,100 patients, who were 40 - 80 years of age who had a diagnosis of COPD, with pre bronchodilator forced expiratory volume in 1 second (FEV1) of < 60% and 10% reversibility of predicted FEV1, meeting the European Respiratory Society definitions for COPD were randomised from 439 sites in 42 countries to one of the following 4 treatment groups:3

-- Placebo
-- Salmeterol (50 µg)
-- Fluticasone propionate (500 µg)
-- Seretide (SFC, 50/500 µg), all inhaled twice daily via the Diskus™

In all treatment arms patients were allowed to take other medications to treat COPD symptoms including anticholinergics, theophylline and salbutamol (similar usage was seen across treatment arms). Patients were instructed not to take inhaled corticosteroids, long term oral corticosteroids or long-acting bronchodilators while enrolled in the study.

The primary end point of TORCH was the reduction in all-cause mortality, comparing SFC with placebo. Secondary endpoints include:3

-- COPD morbidity (as measured by the rate of exacerbations [moderate requiring systemic corticosteroids and/or antibiotics or severe requiring hospitalisation])
-- Quality of life (as measured by St George's Respiratory Questionnaire (SGRQ))

In the TORCH trial, published in the New England Journal of Medicine, the reduction in all-cause mortality between SFC and placebo groups did not meet the pre-specified significance level. In the NEJM paper, the authors suggest that the lower than anticipated number of deaths and the high withdrawal rate in patients receiving placebo, who were free to receive active therapy subsequently, including Seretide, may have contributed to the final results not reaching statistical significance.3

About Seretide

Seretide is a combined treatment of fluticasone propionate, an inhaled corticosteroid and salmeterol, a long acting bronchodilator. Each component targets different aspects of the pathophysiology of COPD a multi-component disease with inflammation at the core.

The inflammation seen in patients with COPD is present even in the early stages of the disease and is associated with disease progression.8 Seretide has been shown to have a broad range of anti-inflammatory effects in COPD which are greater than those seen with inhaled corticosteroids (ICS) in single treatment.9, 10

About GlaxoSmithKline

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

http://www.gsk.com

References

1. British Lung Foundation. 'Missing Millions' Campaign, World COPD Day 2006

2. Seretide Summary of Product Characteristics

3. Calverley, PMA et al on behalf of the TORCH investigators. Salmeterol and fluticasone propionate and survival in Chronic Obstructive Pulmonary Disease. NEJM 2007; 356: 775-789

4. Thompson WL. Pulmonary Disease. In: Stoudemire A, Fogel BS, Greeberg DB, eds. Psychiatric care of the medical patient. 2nd ed. New York, NY: Oxford University Press; 2000:757-774.

5. Kunik ME, Roundy K, Veazey C, Souchek J, Richardson P, Wray NP, Stanley MA. Surprisingly High Prevalence of Anxiety and Depression in Chronic Breathing Disorders. Chest 2005; 127;1205-1211

6. Department of Health Annual report 2005. The Chief Medical Officer on the state of public health'.

7. European Respiratory Society, European Lung Federation, European Lung White Book, 2003

8. Hogg JC, Chu F. The Nature of Small-Airway Obstruction in Chronic Obstructive Pulmonary Disease. NEMJ 2004; 350;26

9. Yamauchi Y, Christodoulopoulos P, Olivenstein R, Maltais F, Bourbeau J, Hamid Q. The Effect of Salmeterol/Fluticasone Combination on Airway Inflammation in COPD Compared to Fluticasone. PATS 2006; 3(abstracts issue): A113

10. Barnes N, Qiu Y, Pavord I et al. Antinflammatory Effects of Salmeterol/Fluticasone Proprionate in Chronic Obstructive Lung Disease. Am J Respir Crit Care Med 2006; 173: 736-743

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