GSK’s industry-leading respiratory research and scientific innovation showcased at ATS conference

Dr. Hal Barron, Chief Scientific Officer and President R&D, GSK said: “We have a comprehensive portfolio of innovative respiratory medicines that are used by millions of patients worldwide who suffer from asthma and chronic obstructive pulmonary disease (COPD). The data presented at ATS demonstrate the breadth of activities being undertaken by GSK to improve patient outcomes and generate evidence that will help answer some of the key questions in respiratory medicine.”

Leading research efforts to support the role of biologics in respiratory diseases

GSK is at the forefront of biologics respiratory research, using targeted approaches to improve the management of a range of respiratory disease sub-types. This includes the development of first-in-class anti-IL5 biologic Nucala (mepolizumab) for the treatment of severe eosinophilic asthma and ongoing investigation of its potential in other eosinophilic driven diseases.

• New evidence from COLUMBA, the first long-term study of an anti-IL5 biologic treatment, will be presented evaluating the effect of Nucala on exacerbations and asthma control for up to 4.5 years.
• Meta-analyses of the METREX and METREO studies evaluating the use of mepolizumab in the treatment of eosinophilic COPD will also be profiled.

Defining the right COPD treatment for patients

The landmark IMPACT study was the first to directly compare single inhaler triple therapy to members of two different classes of dual therapy with all treatments delivered once-daily and in the same inhaler type, advancing the evidence that informs the treatment of patients with COPD. 

• Results from IMPACT will be presented showing the effect of once-daily single inhaler triple therapy Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol ‘FF/UMEC/VI’) on endpoints including exacerbations, lung function and quality of life.
• Evidence of the effect on on-treatment, all-cause mortality will also be shared.

Optimising medicine delivery

GSK’s Ellipta inhaler platform was developed to optimise medicine delivery in a consistent device across a portfolio of once-daily medicines for COPD and asthma. 

• New results from patient-handling studies will be presented assessing outcomes for single Ellipta inhaler use compared to multiple inhaler use.
• Further results from patient preference and inhaler teaching time studies will also be presented.

Developing medicines for the future

GSK is working to target underlying disease-driving biological processes to shape development of future generations of medicines.

• New research exploring the potential of inhaled PI3Kδ inhibitor nemiralisib in treating acute COPD exacerbations will be presented, including results on lung function and re-exacerbations in exacerbating COPD patients.
• Emerging evidence from the Galaxy collaboration programme will provide new insights into the pathophysiological features of respiratory diseases and disease progression risk factors.

In total, GSK will present data from 61 abstracts, including five oral presentations and 42 poster presentations.

Table of key abstracts:

Medicine	Title	Author	Abstract / poster numbers
Leading research efforts to support the role of biologics in respiratory diseases
mepolizumab (SB240563)	Effect of mepolizumab (100 mg subcutaneous) on exacerbation rate in patients with severe eosinophilic asthma by omalizumab eligibility (US criteria), and immunoglobulin E and eosinophilic subgroups	Liu M, et al.	A7657 / P920
mepolizumab (SB240563)	Long-term safety of mepolizumab in patients with severe eosinophilic asthma: the COLUMBA study	Ortega H, et al.	A1367 / P892
mepolizumab (SB240563)	Durability of clinical response following long-term treatment with mepolizumab in patients with severe eosinophilic asthma: the COLUMBA study	Albers F, et al.	A1372 / P897
mepolizumab (SB240563)	EGPA Patient Characteristics and Clinical Response to Mepolizumab Compared to Placebo	Steinfeld S, et al.	A3012 / P644
mepolizumab (SB240563)	Characteristics and outcomes of COPD patients with blood eosinophils ≥150 cells/µL who continue to exacerbate whilst treated with multiple inhaler triple therapy	Müllerová H, et al.	A3137 / P1369
mepolizumab (SB240563)	Mepolizumab for eosinophilic chronic obstructive pulmonary disease (COPD): a meta-analysis of METREX and METREO exacerbation endpoints	Bafadhel M, et al.	A5912
mepolizumab (SB240563)	Mepolizumab for eosinophilic chronic obstructive pulmonary disease (COPD): a meta-analysis of METREX and METREO patient-reported outcomes, response to therapy and lung function	Chapman K, et al.	A4230 / 604
mepolizumab (SB240563)	Eosinophilic Granulomatosis with Polyangiitis (EGPA) prevalence and oral corticosteroid (OCS) use among asthma patients in a US commercial claims database	Gokhale M, et al.	A4846 / P23
mepolizumab (SB240563)	Do Blood Eosinophils Play a Role in Burden of Illness in Patients with COPD?	Hahn B, et al.	A5001 / P1412
Defining the right COPD treatment for patients
fluticasone furoate/vi/umec (GSK2834425)	Single Inhaler Triple Therapy (ICS/LAMA/LABA) Versus Dual Therapy (ICS/LAMA or LABA/LAMA) in Patients with COPD at Risk of Exacerbations: Efficacy and Safety Results of the Phase III IMPACT Trial	Lipson D, et al.	A1014
fluticasone furoate/vi/umec (GSK2834425)	Reduction in All-Cause mortality with Single Inhaler Triple Therapy (FF/UMEC/VI) versus Dual Therapy (FF/VI and UMEC/VI) in Patients with COPD: Prespecified analysis of the Phase III IMPACT trial	Lipson D, et al.	A1015
Optimising medicine delivery
fluticasone furoate/vi/umec (GSK2834425)	Inhaler errors in COPD: a comparison of using a single inhaler type Ellipta inhaler versus multiple inhaler types	Van Der Palen J, et al.	A4994 / P1405
fluticasone furoate/vi/umec (GSK2834425)	Time to achieve correct inhaler use in patients with COPD: a comparison of the single Ellipta inhaler with dual inhaler combinations	Van Der Palen J, et al..	A4993 / P1404
fluticasone furoate/vi/umec (GSK2834425)	Preference in patients with COPD: a comparison of the single inhaler type Ellipta versus dual inhaler combinations	Van Der Palen J, et al.	A4992 / P1403
Developing medicines for the future
nemiralisib (GSK2269557)	Inhaled PI3Kdelta Inhibitor Nemiralisib Improves Lung Function and Reduces Re-Exacerbations in Exacerbating Chronic Obstructive Pulmonary Disease (COPD) patients (PII116678)	Hessel E, et al.	A6169
Galaxy	Elastin degradation is not just elastin degradation: serological assessment of 3 different proteolytic fragments of elastin predicts mortality and relates to different pathophysiologic events in the Eclipse COPD cohort	Ronnow S, et al.	A5910
Galaxy	Respiratory symptoms and health status in patients with COPD: results from the acute exacerbation and respiratory infections (AERIS) study	Sung R, et al.	A2757 / 611
Galaxy	Baseline characteristics of adults with mild-to-moderate asthma in two control cohorts in contrasting geographical locations: ProAR (Brazil) and U-BIOPRED (Europe)	Davis M, et al.	A1907 / P1105

About asthma

Asthma is a chronic lung disease that inflames and narrows the airways.  Asthma affects 358 million people worldwide. Despite medical advances, more than half of patients continue to experience poor control and significant symptoms impacting their daily life. It is estimated that 5-10% of all asthma patients have severe asthma.

The causes of asthma are not completely understood but likely involve an interaction between a person’s genetic make-up and the environment. Key risk factors are inhaled substances that provoke allergic reactions or irritate the airways.

About COPD

COPD is a progressive lung disease that is thought to affect around 384 million people worldwide.

For people living with COPD, the inability to breathe normally can consume their daily lives and make simple activities, like walking upstairs, an everyday struggle. Patients with COPD suffer from symptoms of breathlessness and many have a significant risk of exacerbations. Managing these aspects of the disease drives physician treatment choice.

Long-term exposure to inhaled irritants that damage the lungs and the airways are usually the cause of COPD. Cigarette smoke, breathing in second hand smoke, air pollution, chemical fumes or dust from the environment or workplace can all contribute to COPD. Most people who have COPD are at least 40 years old when symptoms begin.

Every person with COPD is different, with different needs, different challenges and different goals. Understanding this and providing support to help meet these needs is the foundation of GSK’s work.

GSK’s commitment to respiratory disease

GSK has led the way in developing innovative medicines to advance the management of asthma and COPD for nearly 50 years. Over the last five years we have launched six innovative medicines responding to continued unmet patient need, despite existing therapies. This is an industry-leading portfolio in breadth, depth and innovation, developed to reach the right patients, with the right treatment.

We remain at the cutting-edge of scientific research into respiratory medicine, working in collaboration with patients and the scientific community to offer innovative medicines aimed at helping to treat patients’ symptoms and reduce the risk of their disease worsening. While respiratory diseases are clinically distinct, there are important pathophysiological features that span them, and our ambition is to have the most comprehensive portfolio of medicines to address a diverse range of respiratory diseases. To achieve this, we are focusing on targeting the underlying disease-driving biological processes to develop medicines with applicability across multiple respiratory diseases. This approach requires extensive bioinformatics, data analytic capabilities, careful patient selection and stratification by phenotype in our clinical trials.

About Nucala (mepolizumab)

Nucala 100mg is the market leading biologic treatment for patients with severe eosinophil asthma. It is approved in over 40 countries including the EU, US, and Japan and has been prescribed to over 18,000 patients in the US. It has been studied in over 3,000 patients in 16 clinical trials across a number of eosinophilic conditions. Nucala 300mg was recently approved in the US for the treatment of adult patients with a rare disease called eosinophilic granulomatosis with polyangiitis (EGPA). An sBLA has also been filed for the treatment in patients with chronic obstructive pulmonary disease and is currently being investigated for severe hypereosinophilic syndrome and nasal polyposis.

In the US, Nucala (100mg fixed dose subcutaneous injection of mepolizumab) is licensed as an add-on maintenance treatment for patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. Nucala (3x 100mg subcutaneous injection of mepolizumab) is licensed for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA). Nucala is not approved for the relief of acute bronchospasm or status asthmaticus. Full US Prescribing Information is available at US Prescribing Information Nucala.

In the EU, Nucala (100mg fixed dose subcutaneous injection of mepolizumab) is licensed as an add-on treatment for severe refractory eosinophilic asthma in adult patients. For the EU Summary of Product Characteristics for Nucala, please visit: www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003860/WC500198037.pdf

Important Safety Information for Nucala

The following information is based on the US Prescribing Information for Nucala. Please consult the full Prescribing Information for all the labelled safety information for Nucala.

CONTRAINDICATIONS

Nucala should not be administered to patients with a history of hypersensitivity to mepolizumab or excipients in the formulation.

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions

Hypersensitivity reactions (e.g. anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, rash) have occurred following administration of Nucala. These reactions generally occur within hours of administration but in some instances can have a delayed onset (i.e. days). In the event of a hypersensitivity reaction, Nucala should be discontinued.

Acute Asthma Symptoms or Deteriorating Disease                                                  

Nucala should not be used to treat acute asthma symptoms, acute exacerbations, or acute bronchospasm.

Opportunistic Infections: Herpes Zoster

In controlled clinical trials, 2 serious adverse reactions of herpes zoster occurred in subjects treated with Nucala compared to none in placebo. Consider varicella vaccination if medically appropriate prior to starting therapy with Nucala.

Reduction of Corticosteroid Dosage

Do not discontinue systemic or inhaled corticosteroids (ICS) abruptly upon initiation of therapy with Nucala. Decreases in corticosteroid doses, if appropriate, should be gradual and under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Parasitic (Helminth) Infection

It is unknown if Nucala will influence a patient’s response against parasites. Treat patients with pre-existing helminth infections before initiating therapy with Nucala. If patients become infected while receiving treatment with Nucala and do not respond to anti-helminth treatment, discontinue treatment with Nucala until infection resolves.

ADVERSE REACTIONS

The most common adverse reactions (≥3% and more common than placebo) reported in the first 24 weeks of two clinical trials with Nucala (and placebo) were: headache, 19% (18%); injection site reaction, 8% (3%); back pain, 5% (4%); fatigue, 5% (4%); influenza, 3% (2%); urinary tract infection 3% (2%); abdominal pain upper, 3% (2%); pruritus, 3% (2%); eczema, 3% (<1%); and muscle spasm, 3% (<1%).

Systemic Reactions, including Hypersensitivity Reactions:  In 3 clinical trials, 3% of subjects who received Nucala experienced systemic (allergic and nonallergic) reactions compared to 5% in the placebo group. Systemic allergic/hypersensitivity reactions were reported by 1% of subjects who received Nucala compared to 2% of subjects in the placebo group. Manifestations included rash, pruritus, headache, and myalgia. Systemic nonallergic reactions were reported by 2% of subjects who received Nucala and 3% of subjects in the placebo group. Manifestations included rash, flushing, and myalgia. A majority of the systemic reactions were experienced on the day of dosing. Reports of anaphylaxis have been received postmarketing.

Injection site reactions (e.g. pain, erythema, swelling, itching, burning sensation) occurred at a rate of 8% in subjects treated with Nucala compared with 3% in subjects treated with placebo.

USE IN SPECIFIC POPULATIONS

The data on pregnancy exposures from the clinical trials are insufficient to inform on drug-associated risk. Monoclonal antibodies, such as mepolizumab, are progressively transported across the placenta in a linear fashion as pregnancy progresses; therefore, potential effects on a foetus are likely to be greater during the second and third trimesters of pregnancy.

About Trelegy Ellipta (FF/UMEC/VI)

FF/UMEC/VI is the first COPD treatment to provide a combination of three molecules in a single inhaler that only needs to be taken in a single inhalation, once a day. It contains fluticasone furoate, an inhaled corticosteroid, umeclidinium, a long-acting muscarinic antagonist; and vilanterol, a long-acting beta2-adrenergic agonist, delivered in GSK’s Ellipta dry powder inhaler, which is used across the entire portfolio of inhaled COPD medicines.

Data from across multiple clinical programmes have demonstrated the benefit of the molecules in FF/UMEC/VI both alone and in combination, for the treatment of COPD.

FF/UMEC/VI is approved in the US for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema. It is also indicated to reduce exacerbations of COPD in patients with a history of exacerbations. It is not indicated for relief of acute bronchospasm or for the treatment of asthma.

Full US Prescribing Information, including Patient Information is available at:

https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Trelegy/pdf/TRELEGY-PI-MG-IFU.PDF

FF/UMEC/VI was approved for use in Europe in November 2017 as a maintenance treatment in adult patients with moderate to severe COPD who are not adequately treated by a combination of an inhaled corticosteroid and a long-acting beta2-agonist. The European Summary of Product Characteristics is available at: https://www.medicines.org.uk/emc/medicine/34357

Regulatory applications for once-daily single inhaler triple therapy FF/UMEC/VI have been submitted and are undergoing assessment in a number of other countries.

Important Safety Information (ISI) for Trelegy Ellipta

The following ISI is based on the Highlights section of the US Prescribing Information for FF/UMEC/VI. Please consult the full Prescribing Information for all the labelled safety information. 

Trelegy Ellipta is contraindicated in patients with severe hypersensitivity to milk proteins or any of the ingredients.

LABA monotherapy increases the risk of serious asthma-related events.

Trelegy Ellipta should not be initiated in patients experiencing episodes of acutely deteriorating COPD. Do not use Trelegy Ellipta to treat acute symptoms.

Trelegy Ellipta should not be used in combination with other medicines containing LABA because of risk of overdose.

Candida albicans infection of the mouth and pharynx has occurred in patients treated with fluticasone furoate, a component of Trelegy Ellipta. Monitor patients periodically. Advise the patient to rinse his/her mouth with water without swallowing after inhalation to help reduce the risk.

There is an increased risk of pneumonia in patients with COPD taking Trelegy Ellipta. Monitor patients for signs and symptoms of pneumonia.

Patients who use corticosteroids are at risk for potential worsening of infections (e.g. existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex). Use Trelegy Ellipta with caution in patients with these infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients.

There is a risk of impaired adrenal function when transferring from systemic corticosteroids. Taper patients slowly from systemic corticosteroids if transferring to Trelegy Ellipta.

Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage of Trelegy Ellipta in susceptible individuals. If such changes occur, consider appropriate therapy.

If paradoxical bronchospasm occurs, discontinue Trelegy Ellipta and institute alternative therapy.

Use Trelegy Ellipta with caution in patients with cardiovascular disorders because of beta-adrenergic stimulation.

Assess patients for decrease in bone mineral density initially and periodically thereafter after prescribing Trelegy Ellipta.

Close monitoring for glaucoma and cataracts is warranted in patients taking Trelegy Ellipta. Worsening of narrow-angle glaucoma may occur. Use with caution in patients with narrow-angle glaucoma and instruct patients to contact a healthcare provider immediately if symptoms occur.

Worsening of urinary retention may occur in patients taking Trelegy Ellipta. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction and instruct patients to contact a healthcare provider immediately if symptoms occur.

Use Trelegy Ellipta with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis.

Be alert to hypokalemia and hyperglycemia in patients taking Trelegy Ellipta.

The most common adverse reactions reported for Trelegy Ellipta (incidence ≥1%) are upper respiratory tract infection, pneumonia, bronchitis, oral candidiasis, headache, back pain, arthralgia, influenza, sinusitis, pharyngitis, rhinitis, dysgeusia, constipation, urinary tract infection, diarrhea, gastroenteritis, oropharyngeal pain, cough, and dysphonia.

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GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D Principal risks and uncertainties in the company's Annual Report on Form 20-F for 2017.