GSK’s strong science prominent at ATS 2019

Issued: Thursday 16 May 2019, London UK

More than 70 GSK abstracts presented

GlaxoSmithKline plc (LSE/NYSE: GSK) will present more than 70 abstracts at the American Thoracic Society (ATS) International Conference 17-22 May, Dallas, US, providing robust, scientific data to further increase the competitiveness of its comprehensive portfolio of approved respiratory medicines, demonstrating its continued commitment to patients living with respiratory diseases.

Updates include data on evolving areas of science, showing GSK’s ongoing progress in respiratory research as the company marks 50 years of innovation following the launch of Ventolin, the first modern inhaled medicine, in 1969. Over the last six years the company has launched six innovative medicines responding to a greater understanding of the heterogeneity within respiratory diseases and the need for treatments that can target the differing needs of patients.

Highlights from GSK at this year’s ATS will include an update to the all-cause mortality data from the landmark InforMing the Pathway of COPD Treatment (IMPACT) study for Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol or FF/UMEC/VI). Data includes previously missing or censored vital status data with results presented now accounting for 99.6% of the total intention to treat study population. (Study 116855, NCT02164513).

GSK is also presenting several abstracts providing additional clinical evidence for GSK’s anti-IL 5 monoclonal antibody, Nucala (mepolizumab), in severe eosinophilic asthma (SEA) and eosinophilic granulomatosis with polyangiitis (EGPA). Additionally, data will be presented for an investigative use, chronic obstructive pulmonary disease (COPD), where GSK will be initiating a phase III trial in the second half of 2019.

Clinical data supporting the regulatory submission for potential at-home administration options for Nucala will be presented, including real-world patient experience and preference data. (Study 204959; NCT03099096 and 205667; NCT03021304).

Results of the Early MAXimal bronchodilation for improving COPD stability (EMAX) trial, comparing efficacy of Anoro Ellipta (umeclidinium/vilanterol, UMEC/VI), with Incruse Ellipta (umeclidinium) and Serevent (salmeterol) in symptomatic low exacerbation risk patients with COPD not considered appropriate for ICS-containing therapy (Study 201749, NCT03034915) are also amongst GSK’s key data presentations.

Key GSK abstracts to be presented at ATS 2019

Product

Title

Author

Presentation Details

Abstract / poster numbers

Fluticasone furoate/umec /vi (GSK2834425)

Preventing Clinically Important Deterioration (CID) of COPD with Single-inhaler Triple Therapy Fluticasone Furoate/Umeclidinium/Vilanterol: A Prospective Analysis of the IMPACT trial

Meilan K. Han, Gerald J. Criner, Mark T. Dransfield, David M.G. Halpin, C. Elaine Jones, Sally Kilbride, Peter Lange, David A. Lipson, David A. Lomas, Fernando J. Martinez, Ian Naya, Steven J. Pascoe, Robert A. Wise, Dave Singh

A102 -  COPD: THERAPY 
RAPiD: Rapid Abstract Poster Discussion Session
Sunday May 19, 2019 2:15 PM - 4:15 PM
Room C141/C143/C149 (Level 1), KBHCCD
Poster viewing time: 2:15-2:45pm
Poster discussion time 2:45-4:15 pm

A2438
204

Reduction in the risk of all-cause mortality with fluticasone furoate/umeclidinium/vilanterol compared to umeclidinium/vilanterol in IMPACT including previously missing or censored vital status data

David A. Lipson, Gerard Criner, Nicola C. Day, Mark T. Dransfield, David Halpin, MeiLan K. Han, C. Elaine Jones, Sally Kilbride, Peter Lange, David A. Lomas, Pamela Manchester, Fernando J. Martinez, Dawn Midwinter, Andrea Morris, Steve Pascoe, David Singh, Robert A. Wise

A102 -  COPD: THERAPY
RAPiD: Rapid Abstract Poster Discussion Session
Sunday May 19, 2019 2:15 PM - 4:15 PM
Room C141/C143/C149 (Level 1), KBHCCD
Poster Viewing Time 2:15-2:45pm
Poster Discussion Time 2:45-4:15pm

A7344
221

Exacerbation costs associated with FF/UMEC/VI therapy in COPD compared with FF/VI and UMEC/VI therapy

Michael Bogart, Sari Hopson, Huai-Che Shih, Richard H. Stanford, Anna D. Coutinho

D93 -  PAYING FOR CARE IN PULMONARY DISEASES
Mini Symposium
Wednesday May 22, 2019 1:30 PM - 3:30 PM
Room C146 (Level 1), KBHCCD
Presentation time: 14:30-14:45

A7034

Fluticasone furoate/vilanterol trifenatate (GSK2285997)

Inhaled Corticosteroids Dose Regimens: Therapeutic Relevance of Lipophilicity, Solubility, Dissolution and Absorption from the Lung

P. T. Daley-Yates

B45 -  COPD: TREATMENT
Thematic Poster Session
Monday May 20, 2019 9:15 AM - 4:15 PM
Area D (Hall F, Level 2), KBHCCD
Poster viewing time 11:15am-1:00pm

A3331
P520

HO-16-16516 Controller adherence and albuterol use among adult patients with asthma on once or twice-daily ICS/LABA therapy using clip-on sensor technology to assess outcomes

Richard H Stanford, Carlyne Averell, Phaedra T. Johnson, Erin Buysman, Maureen Carlyle

D22 - REAL WORLD MEDICATION USE IN PULMONARY DISEASES
RAPiD: Rapid Abstract Poster Discussion Session
Wednesday May 22, 2019 9:15 AM - 11:15 AM
Trinity Ballroom 5-7 (Level 3), Omni Dallas Downtown
Poster viewing time 9:15-9:45am
Poster discussion time 9:45-11:15am

A5929
1011

HO-16-16516 Adherence and asthma control in patients using FF/VI with and without using a sensor that monitors adherence

Richard H Stanford, Carlyne Averell, Phaedra T Johnson, Erin K Buysman, Maureen Carlyle

D22 -  REAL WORLD MEDICATION USE IN PULMONARY DISEASES
RAPiD: Rapid Abstract Poster Discussion Session
Wednesday May 22, 2019 9:15 AM - 11:15 AM
Trinity Ballroom 5-7 (Level 3), Omni Dallas Downtown
Poster viewing time 9:15-9:45am
Poster discussion time 9:45-11:15am

A5930
1012

Mepolizumab  (SB240563)

Mepolizumab (SB240563) 

The long-term efficacy and safety of mepolizumab in children from 6 to 11 years of age with severe eosinophilic asthma

Steinfeld J, Gupta A, Ikeda M, Geng B, Azmi J, Price R, Bradford E, Yancey S

D105 -  IMPROVING PEDIATRIC ASTHMA CONTROL AND OUTCOMES
RAPiD: Rapid Abstract Poster Discussion Session
Wednesday May 22, 2019 1:30 PM - 3:30 PM
Dallas Ballroom E-F (Level 3), Omni Dallas Downtown
Poster viewing time 1:30-2:00pm
Poster discussion time 2:00-3:30pm

A7192
817

Self-administration of Mepolizumab Liquid Using a Single-Use Prefilled Autoinjector

Chapman K, Bernstein D, Pavord I, Follows R, Bentley J, Pouliquen I, Bradford E

A32 ‑ ASTHMA: CLINICAL STUDIES II
Thematic Poster Session
Sunday May 19, 2019 9:15 AM ‑ 4:15 PM
Area E (Hall F, Level 2), KBHCCD
Poster viewing time 11:15am-1:00pm

A1305
P696

Mepolizumab prefilled autoinjector and prefilled syringe real world use: the patient experience

Evitt L, Follows R, Bentley J, Williams W, Shalhoub H, Celone M, von Maltzahn R

A32 -  ASTHMA: CLINICAL STUDIES II
Thematic Poster Session
Sunday May 19, 2019 9:15 AM - 4:15 PM
Area E (Hall F, Level 2), KBHCCD
Poster viewing time 11:15am-1:00pm

A1307
P698

Self-administration of Mepolizumab Liquid Using a Single-Use Prefilled Syringe

Bradford E, Bernstein D, Bjermer L, Follows R, Bentley J, Pouliquen I, Bel E

A32 -  ASTHMA: CLINICAL STUDIES II
Thematic Poster Session
Sunday May 19, 2019 9:15 AM - 4:15 PM
Area E (Hall F, Level 2), KBHCCD
Poster viewing time 11:15am-1:00pm

A1306
P697

Efficacy of Mepolizumab in Patients with Severe Eosinophilic Asthma by Age of Asthma Onset: Meta-analysis of Two Phase III Trials

Albers F, Hanania N, Kraft M, Bratton D, Bradford E, Smith S, Prazma C, Brusselle G

A31 -  ASTHMA: CLINICAL STUDIES I
Thematic Poster Session
Sunday May 19, 2019 9:15 AM - 4:15 PM
Area E (Hall F, Level 2), KBHCCD
Poster viewing time 11:15am-1:00pm

A1274
P662

Efficacy of Mepolizumab in Patients with Severe Eosinophilic Asthma and Concomitant Aspirin-Exacerbated Respiratory Disease: Meta-analysis of Two Phase III Trials

Laidlaw T, Albers F, Bratton D, Bradford E, Smith S, Llanos-Ackert JP, Taille C, Lugogo N

B21 -  SEVERE ASTHMA: CLINICAL AND MECHANISTIC STUDIES
RAPiD: Rapid Abstract Poster Discussion Session
Monday May 20, 2019 9:15 AM - 11:15 AM
Room D222-D224 (Level 2), KBHCCD
Poster viewing time 9:15-9:45am
Poster discussion time 9:45-11:15am

A2672
507

 

Burden of Illness Associated with Eosinophilic Granulomatosis with Polyangiitis (EGPA, formerly Churg-Strauss Syndrome) in the United States: Evidence from Two Administrative Claims Databases

Bell C, Shen Q, Sloane J, Katz A

D24 -  AUTOIMMUNE DISEASE, DRUG-INDUCED, AND TRANSPLANT

Poster Discussion Session

Wednesday May 22, 2019 9:15 AM - 11:15 AM

Room C140/C142 (Level 1), KBHCCD

Poster viewing time 9:15-10:00am

Poster discussion time 10:00-11:15am

A5984

122

Anoro Ellipta (umeclidinium/vilanterol trifenatate) (GSK2592356)

Comparative Efficacy of Umeclidinium/Vilanterol, Umeclidinium and Salmeterol in Symptomatic Patients with Chronic Obstructive Pulmonary Disease Free of Inhaled Corticosteroids: The EMAX Trial

Maltais F,  Bjermer L, Kerwin E, Vogelmeier C, Watkins M, Tombs L, Naya I, Boucot I, Lipson D, Compton C, Jones P

A102 -  COPD: THERAPY (RAPiD: Rapid Abstract Poster Discussion Session)
Date/time: Sunday May 19, 2019 2:15 PM - 4:15 PM
Room C141/C143/C149 (Level 1), KBHCCD
Poster viewing time 2:15-2:45pm
Poster discussion time 2:45-4:15pm

A2446
212

Comparative Efficacy and Safety of Umeclidinium/Vilanterol, Umeclidinium and Salmeterol in Symptomatic Maintenance-naïve and Maintenance-treated Chronic Obstructive Pulmonary Disease: A Prospective Analysis of the EMAX Trial

Bjermer L, Kerwin E, Maltais F, Jones P, Boucot I, Tombs L, Naya I,  Watkins M, Lipson D, Compton C, Vogelmeier C

B45 -  COPD: TREATMENT (Thematic Poster Session)
Date/time: Monday May 20, 2019 9:15 AM - 4:15 PM
Area D (Hall F, Level 2), KBHCCD
Poster viewing time 11:15am-1:00pm

A3317
P506

Preventing Clinically Important Deterioration with Umeclidinium/Vilanterol versus Bronchodilator Monotherapy in Patients with Chronic Obstructive Pulmonary Disease Free of Inhaled Corticosteroids: A Prospective Analysis of the EMAX Trial

Vogelmeier C, Maltais F, Kerwin E, Bjemer L, Naya I, Tombs L, Boucot I, Watkins M, Lipson D, Compton C, Jones P

B45 -  COPD: TREATMENT (Thematic Poster Session)
Date/time: Monday May 20, 2019 9:15 AM - 4:15 PM
Area D (Hall F, Level 2), KBHCCD
Poster viewing time 11:15am-1:00pm

A3315
P504

Comparative Efficacy of Once-Daily Umeclidinium and Twice-Daily Salmeterol in Symptomatic Patients with Chronic Obstructive Pulmonary Disease Free of Inhaled Corticosteroids: Results From the EMAX Trial

 

Kerwin E, Vogelmeier C, Bjermer L, Maltais F, Watkins M, Tombs L, Naya I, Boucot I, Lipson D, Compton C, Jones P

 

B45 -  COPD: TREATMENT (Thematic Poster Session)
Date/time: Monday May 20, 2019 9:15 AM - 4:15 PM
Area D (Hall F, Level 2), KBHCCD
Poster viewing time 11:15am-1:00pm

 

A3320

P509

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

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 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 Nucala (mepolizumab)

Nucala 100mg is the market leading biologic treatment for patients with severe eosinophilic asthma. It is approved in the US, Europe and over 20 other markets and has been prescribed to over 30,000 patients in the US. It has been studied in over 3,000 patients in 16 clinical trials across a number of eosinophilic conditions.

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 and in paediatric patients aged six up to 17 years. For the EU Summary of Product Characteristics for Nucala, please visit: http://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

Herpes zoster infections have occurred in patients receiving NUCALA. 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

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.

ADVERSE REACTIONS: EGPA

In a 52-week clinical trial in patients with EGPA receiving 300 mg of NUCALA, no additional adverse reactions were identified to those reported in severe asthma clinical trials.

Systemic Reactions, including Hypersensitivity Reactions: Percentages of subjects who experienced systemic (allergic and nonallergic) reactions were 6% for subjects receiving 300 mg of NUCALA and 1% for placebo. Manifestations of systemic allergic reactions included rash, pruritus, flushing, fatigue, hypertension, warm sensation in trunk and neck, cold extremities, dyspnea, and stridor. The reported manifestation of systemic nonallergic reactions was angioedema. Two of the four (50%) systemic reactions in subjects receiving 300 mg of NUCALA were experienced on the day of dosing.

Injection site reactions (eg, pain, erythema, swelling) occurred in 15% of subjects treated with 300 mg of NUCALA versus 13% 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 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 in the US

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.

About BREO ELLIPTA 

In the US BREO ELLIPTA is indicated for the once-daily treatment of asthma in patients aged 18 years and older uncontrolled on a long-term control medication (e.g. an inhaled corticosteroid (ICS)) or whose disease warrants an ICS and long-acting beta2-adrenergic agonist (LABA).

BREO 100/25 is indicated for the long-term, once-daily for maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema, and for reducing COPD exacerbations in patients with a history of exacerbations. BREO 100/25 is the only strength indicated for COPD.

BREO is NOT indicated for the relief of acute bronchospasm.

Safety Information for BREO Ellipta*

CONTRAINDICATIONS

  • BREO is contraindicated for primary treatment of status asthmaticus or other acute episodes of chronic obstructive pulmonary disease (COPD) or asthma where intensive measures are required.
  • BREO is contraindicated in patients with severe hypersensitivity to milk proteins or demonstrated hypersensitivity to fluticasone furoate, vilanterol, or any of the excipients.

WARNINGS AND PRECAUTIONS

  • LABA monotherapy for asthma increases the risk of asthma-related death and the risk of asthma-related hospitalizations in pediatric and adolescent patients. These findings are considered a class effect of LABA monotherapy. When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone.
  • BREO should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD or asthma.
  • BREO is not a rescue medication and should not be used for the relief of acute bronchospasm or symptoms. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist.
  • BREO should not be used more often or at higher doses than recommended, or with another LABA (eg, salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs, like LABA.
  • Oropharyngeal candidiasis has occurred in patients treated with BREO. Advise patients to rinse the mouth with water without swallowing after inhalation.
  • An increase in the incidence of pneumonia has been observed in subjects with COPD receiving BREO. There was also an increased incidence of pneumonias resulting in hospitalization. In some incidences these pneumonia events were fatal.
    • In replicate 12-month studies of subjects with moderate to severe COPD who had experienced a COPD exacerbation in the previous year, there was a higher incidence of pneumonia reported in subjects receiving BREO 100/25 (6% [51 of 806 subjects]) and BREO 200/25 (7% [55 of 811 subjects]) than in subjects receiving vilanterol 25 mcg (3% [27 of 818 subjects]). There was fatal pneumonia in 1 subject receiving BREO 100/25 and in 7 subjects receiving BREO 200/25 (<1% for each treatment group).
  • In a mortality trial in subjects with moderate COPD and cardiovascular disease, the annualized incidence rate of pneumonia was 3.4 per 100 patient-years for BREO 100/25 vs 3.2 for placebo.
  • Physicians should remain vigilant for the possible development of pneumonia in patients with COPD, as signs and symptoms of pneumonia and COPD exacerbations overlap.
  • Use caution in patients who use corticosteroids as they are at risk for potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. A more serious or even fatal course of chickenpox or measles may occur in susceptible patients.
  • Particular care is needed for patients transferred from systemic corticosteroids to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer. Taper patients slowly from systemic corticosteroids if transferring to BREO.
  • Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage of inhaled corticosteroids in susceptible individuals. If such changes occur, discontinue BREO slowly.
  • Caution should be exercised when considering the coadministration of BREO with long-term ketoconazole and other known strong CYP3A4 inhibitors (eg, ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole) because increased systemic corticosteroid and cardiovascular adverse effects may occur.
  • If paradoxical bronchospasm occurs, discontinue BREO immediately and institute alternative therapy.
  • Hypersensitivity reactions such as anaphylaxis, angioedema, rash, and urticaria may occur after administration of BREO. Discontinue BREO if such reactions occur.
  • Vilanterol can produce clinically significant cardiovascular effects in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, and also cardiac arrhythmias, such as supraventricular tachycardia and extrasystoles. If such effects occur, BREO may need to be discontinued. BREO should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
  • In a mortality trial in subjects with moderate COPD and cardiovascular disease, the annualized incidence rate of cardiovascular adverse events was 2.5 per 100 patient-years for BREO 100/25 vs 2.7 for placebo.
  • Decreases in bone mineral density have been observed with long‐term administration of products containing inhaled corticosteroids. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (eg, anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care. Since patients with COPD often have multiple risk factors for reduced BMD, assessment of BMD is recommended prior to initiating BREO and periodically thereafter.
  • Glaucoma, increased intraocular pressure, and cataracts have been reported in patients with COPD or asthma following the long-term administration of inhaled corticosteroids. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use BREO long term.
  • Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines.
  • Increased blood glucose levels have been reported. Also, be alert to hypokalemia
  • Orally inhaled corticosteroids may reduce growth velocity in children and adolescents.

ADVERSE REACTIONS

  • In a 12-week trial, adverse reactions (≥2% incidence and more common than placebo) reported in subjects taking BREO 100/25 (and placebo) were: nasopharyngitis, 10% (7%); headache, 5% (4%); oropharyngeal pain, 2% (1%); oral candidiasis, 2% (0%); and dysphonia, 2% (0%). In a separate 12-week trial, adverse reactions (≥2% incidence) reported in subjects taking BREO 200/25 (or BREO 100/25) were: headache, 8% (8%); nasopharyngitis, 7% (6%); influenza, 3% (3%); upper respiratory tract infection, 2% (2%); oropharyngeal pain, 2% (2%); sinusitis, 2% (1%); bronchitis, 2% (<1%); and cough, 1% (2%).
  • Additional adverse reactions (≥2% incidence) reported in subjects taking BREO 200/25 in a 24-week trial included viral respiratory tract infection, pharyngitis, pyrexia, and arthralgia; and with BREO 100/25 or 200/25 in a 12-month trial included pyrexia, back pain, extrasystoles, upper abdominal pain, respiratory tract infection, allergic rhinitis, pharyngitis, rhinitis, arthralgia, supraventricular extrasystoles, ventricular extrasystoles, acute sinusitis, and pneumonia.
  • In a 24- to 76-week trial of subjects with ≥1 asthma exacerbations in the past year, asthma-related hospitalizations occurred in 1% of subjects taking BREO 100/25. No asthma-related deaths or intubations were observed.

ADVERSE REACTIONS: BREO 100/25 FOR COPD

  • In subjects with COPD, the most common adverse reactions (≥3% and more common than placebo) reported in two 6‐month clinical trials with BREO 100/25 (and placebo) were nasopharyngitis, 9% (8%); upper respiratory tract infection, 7% (3%); headache, 7% (5%); and oral candidiasis, 5% (2%).
  • In addition to the events reported in the 6-month studies, adverse reactions occurring in ≥3% of the subjects treated with BREO 100/25 in two 1‐year COPD studies included back pain, pneumonia, bronchitis, sinusitis, cough, oropharyngeal pain, arthralgia, influenza, pharyngitis, and pyrexia.
  • In addition to the events reported in the 6-month studies, in a mortality trial (median treatment duration of 1.5 years) in subjects with moderate COPD and cardiovascular disease, adverse reactions occurring in ≥3% of the subjects treated with BREO 100/25 and more common than placebo included pneumonia, back pain, hypertension, and influenza.

DRUG INTERACTIONS

  • Caution should be exercised when considering the coadministration of BREO with long‐term ketoconazole and other known strong CYP3A4 inhibitors. See prior Warning and Precaution regarding CYP3A4 inhibitors.
  • BREO 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 they may potentiate the effect of vilanterol on the cardiovascular system.
  • 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 or asthma.
  • Use with caution in patients taking non–potassium-sparing diuretics, as ECG changes and/or hypokalemia associated with these diuretics may worsen with concomitant beta-agonists.

USE IN SPECIFIC POPULATIONS

  • BREO is not indicated for children and adolescents; the safety and efficacy in patients aged ≤17 years have not been established.
  • Use BREO with caution in patients with moderate or severe hepatic impairment. Fluticasone furoate systemic exposure increased by up to 3-fold in subjects with hepatic impairment. Monitor for corticosteroid-related side effects.

Full US Prescribing Information, including Medication Guide will be available soon at: us.gsk.com. Prior to the updated label being posted online, a copy of the label may be requested from one of the GSK Media or Investor Relations contacts listed in the “GSK Enquiries” section at the end of this document.

BREO ELLIPTA is known as RELVAR ELLIPTA in Europe where it is indicated for the regular treatment of patients aged 12 and over with asthma, where use of a combination product (long-acting beta2-agonist, LABA, and inhaled corticosteroid, ICS) is appropriate: Patients not adequately controlled on both ICS and 'as-needed' short-acting beta2- agonist (SABA).

Full EU prescribing information is available at:  EU Prescribing Information for Relvar 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.