Real-world effectiveness evidence among GSK data presented at ERS 2019

Issued: London, UK

GlaxoSmithKline will for the first time share data on the effectiveness of mepolizumab in severe eosinophilic asthma patients from multiple countries in a real-world setting. Interim results of the REALITI-A study, the first global prospective real-world study of a biologic treatment in patients with severe eosinophilic asthma, will be presented at the European Respiratory Society congress in Madrid (28 September – 2 October).

Real-world studies are designed to test the effectiveness and safety of a medicine compared to existing treatments as patients go about their daily lives, rather than the efficacy and safety of a medicine in a tightly controlled environment, which is how traditional randomised clinical trials are designed.

Patients in real-world studies do not have extensive exclusion criteria applied, for example due to many co-morbid conditions, so results from these studies more closely represent what is seen by clinicians treating patients in everyday clinical practice. Real-world studies can be more complex to run than traditional clinical trials.

Dr Marco Avila, Vice President, Global Medical Therapy Areas Head, said: “We estimate only around 7% of COPD and 3% of asthma patients would be eligible for traditional respiratory clinical trials. So, although real world studies do not replace our need for randomised clinical trials, they are important in helping healthcare decision makers and healthcare professionals to understand better how patients will use and respond to their medicines, through a study population that more closely represents the patients they will see every day.”

In addition to the REALITI-A results, GSK will present results of scientific studies designed to further our understanding of the pathology and biology of respiratory diseases, to advance our ambition of developing next generation medicines and improving care for respiratory patients.

In GSK’s early exploratory science, a presentation (abstract OA3581) will show how understanding the bacterial composition of the lung (also called the microbiome) in COPD patients using a sputum sample test could have relevance in the clinic to assess the risk of poor outcomes in COPD. A second presentation from this collaboration with the University of Dundee provides important insights on the utility of neutrophils, a type of white blood cell, as a biomarker of outcomes in COPD (abstract PA3387).

Other key GSK abstracts include:

Trelegy Ellipta (fluticasone furoate/ umeclidinium /vilanterol; GSK2834425):

• Analysis of IMPACT: is one blood eosinophil count measurement sufficient to predict ICS treatment response in COPD? Bafadhel et al. COPD CLINICAL TRAILS: NEW MOLECULES AND NOVEL INSIGHTS. Oral Presentation, Sunday September 29 2019: 08:30 AM - 10:30 AM, Session 53, Room: 6F. Presentation time: 08:45 AM - 09:00 AM. Abstract OA260.
• The IMPACT Trial: Single Inhaler Triple Therapy vs dual therapies: Consistent benefit across multiple exacerbation endpoints. Han et al. COPD CLINICAL TRIALS: INHALED AND ORAL THERAPIES. Themaic Poster TP-12. Monday September 30 2019: 12:50 PM - 14:40 PM, Session 259. Abstract PA2483.

Anoro Ellipta (umeclidinium/vilanterol; GSK2592356):

• Influence of salbutamol use on symptomatic outcomes with maintenance bronchodilators: a pre-specified analysis of the EMAX trial. Maltais F et. al. NEW TOWARDS OLD THERAPIES IN AIRWAY DISEASES. Oral Presentation. Monday 30 September 2019 10:45 - 12:45, Session 235 Room: 8A, Presentation Time: 12:30-12:45. Abstract OA2108.
• Improving COPD symptoms with umeclidinium/vilanterol and impact of baseline disease severity: the EMAX trial; Maltais F. et. al. COPD CLINICAL TRIALS: INHALED AND ORAL THERAPIES. Themaic Poster TP-12. Monday September 30 2019: 12:50 PM - 14:40 PM, Session 259. Abstract PA2473.
• Symptom improvement over time with umeclidinium/vilanterol versus monotherapy: a post-hoc analysis of the EMAX trial; Kerwin E. et. al. COPD CLINICAL TRIALS: INHALED AND ORAL THERAPIES. Themaic Poster TP-12. Monday September 30 2019: 12:50 PM - 14:40 PM, Session 259. Abstract PA2477

Nucala (mepolizumab; SB240563):

• Real-life experience with mepolizumab in the French early access program for severe eosinophilic asthma. Taillé et al. TREATMENT OF ASTHMA WITH MONOCLONAL ANTIBODIES. Poster Discussion, Sunday September 29 2019: 14:45 PM - 16:45 PM, Session 176, Room: 6B. Abstract PA1652.
• Self-administration of mepolizumab via an autoinjector: the patient experience. Evitt et al. REAL-WORLD EXPERIENCE OF MONOCLONAL ANTIBODIES IN ASTHMA. Thematic Poster TP-14. Monday September 30 2019: 12:50 PM - 14:40 PM, Session 261.
• Mepolizumab self-administration via autoinjector and prefilled syringe: the qualitative patient experience. Evitt et al. REAL-WORLD EXPERIENCE OF MONOCLONAL ANTIBODIES IN ASTHMA. Thematic Poster TP-14. Monday September 30 2019: 12:50 PM - 14:40 PM, Session 261.

About severe asthma and eosinophilic inflammation
Severe asthma is defined as asthma which requires treatment with high dose inhaled corticosteroids (ICS) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy. Severe asthma patients are also often categorised by long-term use of oral corticosteroids (OCS). In a sub-set of severe asthma patients, the over-production of eosinophils (a type of white blood cell) is known to cause inflammation in the lungs. Interleukin-5 (IL-5) is the main promoter of eosinophil growth, activation and survival and provides an essential signal for the movement of eosinophils from the bone marrow into the lung. Studies suggest that approximately 60% of patients with severe asthma have eosinophilic airway inflammation.

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
For 50 years, GSK has led the way in developing medicines that advance the management of asthma and COPD. From introducing the world’s first selective short-acting beta agonist in 1969, to launching six treatments in five years to create today’s industry-leading respiratory portfolio, we continue to innovate so we can reach the right patients, with the right treatment. Working together with the healthcare community, we apply world-class science to discover and understand the molecules that become the medicines of tomorrow. We won’t stand still until the simple act of breathing is made easier for everyone.

About Nucala (mepolizumab)
First approved in 2015 for severe eosinophilic asthma, mepolizumab is the first-in-class monoclonal antibody that targets IL-5. It is believed to work by preventing IL-5 from binding to its receptor on the surface of eosinophils, reducing blood eosinophils without completely depleting them.

Mepolizumab has been developed for the treatment of diseases that are driven by inflammation caused by eosinophils. It has been studied in over 3,000 patients in 21 clinical trials across a number of eosinophilic indications and is the only biologic with 4.8 years of safety and efficacy data in severe eosinophilic asthma (SEA). Mepolizumab is approved (under the brand name Nucala) in the US, Europe and in over 20 other markets, as an add-on maintenance treatment for patients with SEA. It was approved for self-administration by patients aged over 12 in the US and EU in 2019. Mepolizumab is the only anti-IL5 biologic therapy approved for use in asthma patients aged six to 17 years in Europe and the US in SEA. In the US, Japan and Canada and a number of other markets, it is approved as add-on maintenance treatment for patients with EGPA. Mepolizumab is currently being investigated for severe hypereosinophilic syndrome, nasal polyposis and COPD.

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.

Important safety information for Nucala (mepolizumab)
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 new 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 for use in Europe 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

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

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.

Consider referral to an ophthalmologist in patients who develop ocular symptoms or use TRELEGY ELLIPTA long term. 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.

About Anoro Ellipta
Anoro Ellipta (umeclidinium and vilanterol inhalation powder) is a combination of two bronchodilators in GSK’s Ellipta dry powder inhaler. It contains umeclidinium (UMEC), a long-acting muscarinic antagonist (LAMA) and vilanterol (VI), a long-acting beta₂ agonist (LABA). The dose of UMEC/VI is labelled as 55/22mcg in Europe (delivered dose) and 62.5/25mcg in the US (dispensed dose) and is delivered in the Ellipta inhaler.

Important Safety Information for Anoro Ellipta
The following Important Safety Information (ISI) is based on the Highlights section of the Prescribing Information for Anoro Ellipta.  Please consult the full Prescribing Information for all the labeled safety information for Anoro Ellipta.

Long-acting beta₂-adrenergic agonists (LABA), such as vilanterol, increase the risk of asthma-related death. A placebo-controlled trial with another LABA (salmeterol) showed an increase in asthma-related deaths. This finding with salmeterol is considered a class effect of all LABA.  The safety and efficacy of Anoro in patients with asthma have not been established.  Anoro is not indicated for the treatment of asthma. 

Anoro is contraindicated in patients with severe hypersensitivity to milk proteins or any ingredients.

Anoro should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD, or as rescue therapy for the treatment of acute episodes of bronchospasm, which should be treated with an inhaled, short-acting beta₂-agonist.

Anoro should not be used more often than recommended, at higher doses than recommended, or in conjunction with additional medicine containing a LABA, as an overdose may result.

Anoro should be used with caution when considering coadministration with ketoconazole and other known strong cytochrome P450 3A4 inhibitors because increased cardiovascular adverse effects may occur.

Anoro can produce paradoxical bronchospasm, which may be life-threatening.

Anoro should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Anoro should be used with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines.

Anoro should be used with caution in patients with narrow-angle glaucoma. Instruct patients to contact a physician immediately should any signs or symptoms of narrow-angle glaucoma occur.

Anoro should be used with caution in patients with urinary retention, especially in patients with prostatic hyperplasia or bladder neck obstruction.  Instruct patients to contact a physician immediately should any signs or symptoms of urinary retention occur.

Beta-adrenergic agonist medicines may produce significant hypokalemia and transient hyperglycemia in some patients.

The most common adverse reactions (incidence ≥1% and more common than placebo) with Anoro were pharyngitis, sinusitis, lower respiratory tract infection, constipation, diarrhea, pain in extremity, muscle spasms, neck pain, and chest pain.

Beta₂-agonists, such as vilanterol should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval or within 2 weeks of discontinuation of such agents, because the effect of adrenergic agonists on the cardiovascular system may be potentiated.

Use beta‐blockers with caution as they not only block the pulmonary effect of beta‐agonists, such as vilanterol, but may produce severe bronchospasm in patients with COPD.

Use with caution in patients taking non–potassium-sparing diuretics, as electrocardiographic changes and/or hypokalemia associated with non–potassium-sparing diuretics may worsen with concomitant beta-agonists.

Avoid co-administration of Anoro with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects such as cardiovascular effects, worsening of narrow-angle glaucoma, and worsening of urinary retention.

Full US prescribing information is available at: US Prescribing Information for Anoro Ellipta.

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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 2018.