NEJM publishes results of GSK's long-term LABA safety study of Advair ® Diskus® in adults and adolescents with asthma

06 March 2016
Issued: London

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GlaxoSmithKline plc (LSE/NYSE:GSK) today announced publication of results from the 'LABA' (long acting beta2-agonist) safety study, AUSTRI (SAS115359) in the New England Journal of Medicine (NEJM). The study, which reported results in October, compared Advair® Diskus®, a combination of the LABA, salmeterol, and inhaled corticosteroid (ICS), fluticasone propionate (FP), to FP monotherapy, to assess the safety profiles of each medicine when used to treat adolescent and adult patients with asthma. This was assessed by the composite endpoint of serious asthma-related events (deaths, intubations or hospitalisations) and showed that Advair had a safety profile comparable to FP, including no asthma-related deaths in either arm. These results are being simultaneously presented at the American Academy of Asthma, Allergy and Immunology (AAAAI) Congress in Los Angeles, California.

AUSTRI was undertaken as a post-marketing requirement of GSK for the US Food and Drug Administration (FDA). Three other manufacturers of LABA-containing products, which are also indicated for the treatment of asthma, are undertaking identical studies designed to evaluate whether the addition of a LABA to an ICS increased the risk of an event in the composite endpoint of serious asthma-related events in adolescents and adults with asthma. AUSTRI is the first of the large-scale safety studies to report results and was conducted in over 11,000 patients.

Kate Knobil, Chief Medical Officer - Pharmaceuticals at GSK said: "We are pleased that this study, which demonstrates the safety profile of Advair, has now been presented in a well-respected, peer-reviewed journal and also presented at scientific congress. This will give physicians the opportunity to independently review the results of this study."

In addition to the AUSTRI study, GSK is also conducting a second LABA safety study, VESTRI, in children with asthma aged 4 – 11 years of age. This study is on track to report at the end of Q1 2016.

Study Design
AUSTRI Study (SAS115359)
A global, multicentre, randomised stratified, double-blind, parallel-group active comparator, 26 week study in adolescents (12 – 17 years of age) and adults (18 years of age and older) whose asthma warrants treatment with controller asthma therapy. Patients were required to have a history of asthma for at least one year prior to randomisation and experienced a severe asthma exacerbation requiring treatment with oral corticosteroids (or their equivalent) or an asthma-related hospitalisation in the year prior to treatment, but not in the 30 days prior to randomisation.

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Patients were randomised to either fluticasone propionate/salmeterol combination (FSC) or FP. The FP (ICS) treatment dose (100mcg bd, 250mcg bd, 500mcg bd) was determined by the previous use of controller medications and an assessment of the patient's asthma control. Upon entry into the study, patients took part in a screening period of up to two weeks, a randomisation visit (visit 2) followed by a treatment period of 26 weeks where patients attended 3 on-treatment clinic visits. In months where there was not a visit, patients were contacted by telephone. Serious adverse events were collected within six months after the first use of study drug or seven days after the last date of study drug treatment, whichever date was greater. Patients were permitted to use albuterol/salbutamol rescue medication throughout the study.

The primary analysis was to determine whether the addition of LABA to ICS therapy (FSC) is non-inferior to ICS therapy alone (FP) on risk of a composite of serious asthma events (asthma-related hospitalisation, intubation and death). To demonstrate non-inferiority, a predefined margin of 2 was required, meaning the upper limit of the 95% confidence interval needed to be less than two to rule out a doubling in the risk of incidence on FSC compared with FP. All serious asthma related events were adjudicated by an independent committee.

The full results for this study are posted on the GSK Clinical Study Register

About Advair/Seretide
ADVAIR DISKUS is indicated for the treatment of asthma in patients aged 4 years and older.

Long-acting beta2-adrenergic agonists (LABA), such as salmeterol, one of the active ingredients in ADVAIR DISKUS, increase the risk of asthma-related death. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients. Therefore, when treating patients with asthma, physicians should only prescribe ADVAIR DISKUS for patients not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid, or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue ADVAIR DISKUS) if possible without loss of asthma control and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use ADVAIR DISKUS for patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids.

ADVAIR DISKUS is NOT indicated for the relief of acute bronchospasm.

https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Advair_Diskus/pdf/ADVAIR-DISKUS-PI-MG.PDF

Seretide Accuhaler is indicated in Europe in the regular treatment of patients aged 4 and over with asthma, where use of a combination product (long-acting ß2–agonist, LABA, and inhaled corticosteroid, ICS) is appropriate: Patients not adequately controlled on both ICS and 'as-needed' short-acting ß2-agonist (SABA); Patients already adequately controlled on both ICS and LABA.

For the UK Summary of Product Characteristics (SmPC), please visit: https://www.medicines.org.uk/emc/medicine/2317/SPC/Seretide+100,+250,+500+Accuhaler

Important Safety Information for ADVAIR DISKUS
WARNING: ASTHMA-RELATED DEATH
Long-acting beta2-adrenergic agonists (LABA), such as salmeterol, one of the active ingredients in ADVAIR DISKUS, increase the risk of asthma-related death. Data from a large placebo-controlled US trial that compared the safety of salmeterol with placebo added to usual asthma therapy showed an increase in asthma-related deaths in subjects receiving salmeterol (13 deaths out of 13,176 subjects treated for 28 weeks on salmeterol versus 3 deaths out of 13,179 subjects on placebo). Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients.

Therefore, when treating patients with asthma, physicians should only prescribe ADVAIR DISKUS for patients not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid, or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue ADVAIR DISKUS) if possible without loss of asthma control and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use ADVAIR DISKUS for patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids.

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