GlaxoSmithKlineGlaxoSmithKline plc (LSE/NYSE: GSK) and Innoviva, Inc. (NASDAQ: INVA) today announced that the results from the pioneering Salford Lung Study (SLS) have been published in the New England Journal of Medicine (NEJM). This unique study, which reported headline results in May 2016, was designed to evaluate the effectiveness and safety of Relvar® Ellipta® in patients with chronic obstructive pulmonary disease (COPD), compared with their 'usual care' administered in an everyday clinical practice setting. Data from the study were presented at the European Respiratory Society (ERS) International Congress on Sunday 4th September in London, (abstract number OA249).

For the primary endpoint in patients, who had exacerbated in the year before the study, treated with Relvar Ellipta 100/25mcg (fluticasone furoate ‘FF’/vilanterol ‘VI’ or ‘FF/VI’) there was a statistically significant reduction of 8.4% (p=0.025; 95% CI 1.1 to 15.2) in the rate of moderate or severe exacerbations compared with patients receiving ‘usual care’. The majority of these patients in the study on usual care were taking an inhaled corticosteroid (ICS) containing regimen (88%). A similar reduction in exacerbations with FF/VI was seen in those patients on an ICS/long-acting beta2-agonist (LABA) at baseline (8.0%; 95% CI 0.11 to 15.4, p=0.047).

For the intent to treat (ITT) population there were no differences observed between FF/VI and usual care on secondary outcomes measured including the time to first moderate or severe exacerbation and rate of severe exacerbations, the rate of secondary care healthcare contacts and COPD related primary care contacts. There were more primary care contacts overall on FF/VI (12.3% increase, 95% CI 5.4 to19.6). The COPD Assessment Test (CAT), which measures the impact of disease on health status, demonstrated 45% of patients receiving FF/VI improved their CAT score by 2 or more, a clinically relevant improvement, compared to 36% in the usual care group (odds ratio 1.51, 95% CI, 1.28 to 1.77).

The incidence of serious adverse events (SAE) was similar between the groups (29% FF/VI, 27% usual care). For pneumonia, an SAE of special interest, FF/VI demonstrated non-inferiority (7% FF/VI vs 6% usual care). This endpoint was a post-authorisation measure requested by the European Medicines Agency (EMA).

Neil Barnes, Global Medical Head, Respiratory Franchise at GSK said: "In the SLS study we included a broad spectrum of patients who had minimal interventions to see if this would allow us to observe a difference between treatments. The results from SLS provide robust evidence that will enable the healthcare community to begin to understand how the choice of COPD treatment can significantly influence patient outcomes. We are continuing to analyse the data from the study as we know there is so much more we will learn and we look forward to sharing our findings in future publications. I want to thank all of the patients who participated and the partners who collaborated with GSK to make this unique study possible."

Michael W. Aguiar, President and Chief Executive Officer of Innoviva said: "The data being presented at ERS and published in NEJM confirm the effectiveness of Relvar Ellipta compared with not only usual care, but also with those patients who were taking a different medicine in the same ICS/LABA class. These are important data to share with physicians, from a unique study carried out in conditions closely reflecting everyday clinical practice."

The study was made possible through collaboration between GSK, North West e-Health (NWEH), The University of Manchester, Salford Royal NHS Foundation Trust, University Hospital of South Manchester (UHSM), NHS Salford and GPs and community pharmacists in Salford, Trafford and South Manchester.

A second Salford Lung Study is currently being conducted in patients with asthma, with results expected in 2017.

Study Design
The Salford Lung Study is a Phase IIIb multi-centre, open label randomised controlled trial (RCT). The objective of the SLS COPD study was to compare the effectiveness and safety profile of FF/VI 100/25mcg with existing COPD usual care. All suitable patients with COPD at 80 primary care sites in and around Salford and South Manchester were identified from practice databases, and invited to participate in the study by their own GP.

In total, 2802 patients with COPD were randomised 1:1 to receive FF/VI 100/25mcg, with or without a long-acting muscarinic antagonists (LAMA), or to continue to receive usual care. FF/VI was administered once daily via the Ellipta inhaler. Patients who were taking a LAMA in addition to ICS/LABA therapy (triple therapy) who were randomised to the FF/VI group were able to continue to use LAMA therapy in addition to FF/VI. Usual care was taken as advised by the prescribing clinician, and could include single or dual long-acting bronchodilator therapy, inhaled corticosteroid either alone or in combination with a long acting bronchodilator or triple therapy of a LAMA, a LABA and an inhaled corticosteroid.

The Salford Lung Study had minimal exclusion criteria and involved a broad demographic of patients. Patients were followed for a period of 12 months in a normal clinical practice setting using a single electronic medical record (EMR), linking primary care (patients seen by their general practitioner), secondary care (patients seen in a hospital setting) and pharmacy data. Throughout the duration of the study physicians were allowed to modify or switch treatment at any point in the study, as would happen in normal clinical practice, the only exception being a switch from usual care to FF/VI.

The study team was able to monitor all hospital admissions, outpatient and emergency department visits, as well as data from primary care (including all healthcare contacts, out-of-hours activity and prescriptions of antibiotics or oral steroids) via the electronic health-records.

The primary effectiveness endpoint is the mean annual rate of moderate or severe exacerbations, where a moderate exacerbation is defined as the subject receiving an exacerbation-related prescription (given to treat an acute worsening of COPD symptoms) of oral corticosteroid and/or antibiotic with or without NHS contact, not requiring hospitalisation. A severe exacerbation is defined as an exacerbation-related hospitalisation - a direct result of an acute worsening of symptoms of COPD or a prolonged hospitalization as a result of a COPD exacerbation.

What is COPD?
Chronic obstructive pulmonary disease (COPD) is a disease of the lungs that includes chronic bronchitis, emphysema or both. COPD is characterised by obstruction to airflow that interferes with normal breathing. Cigarette smoke, breathing in second-hand smoke, air pollution including biomass fuels, chemical fumes and dust from the environment or workplace can all contribute to COPD.

People with COPD can experience a sudden worsening in symptoms, known as an exacerbation. Symptoms of an exacerbation can include an increase in breathlessness, coughing and mucus production, as well as fever. In these cases, the patient may need to change their medication or even, in some cases, be admitted to hospital. Exacerbations are common; one in three patients with severe COPD and almost half of patients with very severe COPD had frequent exacerbations (two or more in the first year following diagnosis). Every exacerbation can cause permanent lung damage and repeated exacerbations can accelerate the progression of the disease. People with frequent exacerbations have a poorer quality of life and may have an increased risk of death.

Relvar® Ellipta® is known as Breo® Ellipta® in the United States.

About FF/VI 100/25
FF/VI 100/25mcg, under the brand name Breo® Ellipta® 100/25mcg is licensed in the US for:

  • The long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema and to reduce exacerbations of COPD in patients with a history of exacerbations. Breo® Ellipta® 100/25mcg is the only strength indicated for the treatment of COPD.
  • Breo Ellipta100/25mcg is not indicated for the relief of acute bronchospasm.

FF/VI 100/25mcg, under the brand name Relvar® Ellipta® is approved in Europe for:

  • the symptomatic treatment of adults with chronic obstructive pulmonary disease (COPD) with a FEV1<70% predicted normal (post-bronchodilator) with an exacerbation history despite regular bronchodilator therapy.

RELVAR®, BREO® and ELLIPTA® are trade marks of the GlaxoSmithKline group of companies.

About GSK
GSK - 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.

About Innoviva
Innoviva is focused on bringing compelling new medicines to patients in areas of unmet need by leveraging its significant expertise in the development, commercialization and financial management of bio-pharmaceuticals. Innoviva's portfolio is anchored by the respiratory assets partnered with Glaxo Group Limited (GSK), including RELVAR®/BREO® ELLIPTA® and ANORO® ELLIPTA®, which were jointly developed by Innoviva and GSK. Under the agreement with GSK, Innoviva is eligible to receive associated royalty revenues from RELVAR®/BREO® ELLIPTA®, ANORO® ELLIPTA® and, if approved and commercialized, VI monotherapy, as well. In addition, Innoviva retains a 15 percent economic interest in future payments made by GSK for earlier-stage programs partnered with Theravance BioPharma, Inc.