LONDON, UK I February 23, 2017 I GlaxoSmithKline plc (LSE/NYSE:GSK) and Innoviva, Inc. (NASDAQ: INVA) today announced positive headline results from a non-inferiority lung function study, which demonstrated that patients with well-controlled asthma were able to switch to the once-daily Relvar® Ellipta® (fluticasone furoate/vilanterol, FF/VI) 100/25, an inhaled corticosteroid (ICS)/long-acting beta2 agonist (LABA) combination, from the twice-daily Seretide® Accuhaler® (fluticasone propionate /salmeterol, FP/SAL) 250/50, without compromising their lung function.
Patients randomised to FF/VI taken once-daily maintained lung function comparable with those randomised to the twice-daily FP/SAL [difference +19mL (95% CI: -11mL, +49mL], meeting the study’s primary endpoint, based on the lower bound (-11ml) of the 95% confidence interval falling above the non-inferiority margin of -100mL.
A third treatment arm with fluticasone propionate (FP), ICS monotherapy, was included to detect a lung function difference between treatments. Results demonstrated statistically significant differences in favour of the ICS/LABA combinations to FP (p<0.001).
The incidences of on-treatment serious adverse events (SAEs) and adverse events (AEs) of special interest were consistent with the known safety profile of FF/VI, established in asthma patients from other studies.
Eric Dube, SVP and Global Head of Respiratory Franchise, GSK said: At GSK we are constantly searching for ways in which we can help patients better manage their asthma. In this positive study we have demonstrated non-inferiority for once-daily Relvar versus twice-daily Seretide on lung function. This gives us confidence that for patients who struggle taking a twice-daily treatment regimen, there may be a once-daily treatment option available, providing greater physician choice to help patients.”
Mike Aguiar, CEO of Innoviva, Inc., added: “We believe the results of this study are important for patients and physicians. They provide additional evidence that patients with persistent asthma, who are currently treated with a twice-daily ICS/LABA, in this case Seretide, can experience a similar level of benefit in lung function when treated with Relvar Ellipta, which only needs to be taken once a day.”
The study design was agreed with European regulatory authorities. GSK now intends to submit this data to the European Medicines Agency (EMA).
Results from the study will be shared in future publications and presentations.
Study Design
Following a 4-week open-label treatment period with FP/SAL 250/50 twice-daily, patients with well controlled asthma were randomised to receive either FF/VI 100/25 once-daily, FP/SAL 250/50 twice-daily or FP 250 twice-daily in a double-blind, double-dummy manner for 24 weeks at multiple centres in 12 countries.
The primary objective of the study was to demonstrate non-inferiority of Relvar Ellipta 100/25 once-daily with Seretide Accuhaler 250/50 twice-daily in adult and adolescent subjects 12 years of age and older with persistent bronchial asthma, well controlled on twice-daily ICS/LABA. The endpoint for the study was the change from baseline in clinic visit evening FEV1 (pre-brochodilator and pre-dose) at the end of the 24-week treatment period.
To demonstrate the non inferiority of FF/VI vs FP/SAL the lower limit of the 95% confidence interval for the mean difference in change from baseline for evening FEV1 needed to be greater than the pre defined margin of -100mL. This was to rule out the possibility that FF/VI was more than -100mL inferior to FP/SAL.
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.
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 Relvar Ellipta (fluticasone furoate + vilanterol)
Relvar Ellipta is a once-daily dual combination treatment comprising fluticasone furoate, an inhaled corticosteroid and vilanterol, a long-acting beta2-agonist, in a single inhaler, the Ellipta®.
Relvar Ellipta is indicated in Europe in the regular treatment of patients aged 12 and over with asthma, where use of a combination product (long-acting ß2–agonist, LABA, and inhaled corticosteroid, ICS) is appropriate: Patients not adequately controlled on both ICS and ‘as-needed’ short-acting ß2-agonist (SABA).
Full EU prescribing information is available at: EU Prescribing Information for Relvar Ellipta.
Important safety information for Relvar Ellipta in Europe
FF/VI is contraindicated in patients with hypersensitivity to either fluticasone furoate, vilanterol, or any of the excipients.
FF/VI should not be used to treat acute asthma symptoms or an acute exacerbation in COPD, for which a short-acting bronchodilator is required. Increasing use of short-acting bronchodilators to relieve symptoms indicates deterioration of control and patients should be reviewed by a physician.
Patients should not stop therapy with FF/VI in asthma or COPD, without physician supervision since symptoms may recur after discontinuation.
Asthma-related adverse events and exacerbations may occur during treatment with FF/VI. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation of treatment with FF/VI.
Paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. This should be treated immediately with a short-acting inhaled bronchodilator. FF/VI should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary.
Cardiovascular effects, such as cardiac arrhythmias e.g. supraventricular tachycardia and extrasystoles may be seen with sympathomimetic medicinal products including FF/VI. Therefore fluticasone furoate/vilanterol should be used with caution in patients with severe cardiovascular disease.
For patients with moderate to severe hepatic impairment, the 92/22 mcg dose should be used and patients should be monitored for systemic corticosteroid-related adverse reactions. FF/VI 184/22 mcg is not indicated for patients with COPD. There is no additional benefit of the 184/22 mcg dose compared to the 92/22 mcg dose and there is a potential increased risk of pneumonia and systemic corticosteroid-related adverse reactions.
An increase in the incidence of pneumonia has been observed in subjects with COPD receiving FF/VI. There was also an increased incidence of pneumonias resulting in hospitalisation. In some instances these pneumonia events were fatal.
The incidence of pneumonia in patients with asthma was common at the higher dose. In a previous study of FF/VI in asthma the incidence of pneumonia in patients with asthma taking FF/VI 184/22 mcg was numerically higher compared with those receiving FF/VI 92/22 mcg or placebo.
Hyperglycaemia: There have been reports of increases in blood glucose levels in diabetic patients and this should be considered when prescribing to patients with a history of diabetes mellitus.
Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods. These effects are much less likely to occur than with oral corticosteroids. Possible systemic effects include Cushing’s syndrome, Cushingoid features, adrenal suppression, decrease in bone mineral density, growth retardation in children and adolescents, cataract and glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children).
FF/VI should be administered with caution in patients with pulmonary tuberculosis or in patients with chronic or untreated infections. Data from large asthma and COPD clinical trials were used to determine the frequency of adverse reactions associated with FF/VI.
Very common adverse reactions (occurring in >1/10 patients) with FF/VI were headache and nasopharyngitis. Common adverse reactions (occurring in >1/100 to <1/10 patients) were pneumonia, upper respiratory tract infection, bronchitis, influenza, candidiasis of mouth and throat, oropharyngeal pain, sinusitis, pharyngitis, rhinitis, cough, dysphonia, abdominal pain, arthralgia, back pain, fractures, and pyrexia and muscle spasms..Extrasystoles were observed as an uncommon adverse reaction (occurring in >1/1,000 to <1/100 patients). Rare adverse reactions (occurring in >1/10,000 to < 1/1,000) were hypersensitivity reactions (including anaphylaxis, angioedema, rash and urticaria), anxiety, tremor, palpitations, tachycardia and paradoxical bronchospasm. With the exception of pneumonia and fractures, the safety profile was similar in patients with asthma and COPD. During clinical studies, pneumonia and fractures were more frequently observed in patients with COPD.
Relvar Ellipta is known as Breo Ellipta in the United States. Breo Ellipta is licensed in the US for:
- The once-daily treatment of asthma in patients aged 18 years and older.
Long-acting beta2-adrenergic agonists (LABA), such as vilanterol, one of the active ingredients in Breo Ellipta, increase the risk of asthma-related death. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients. Therefore, when treating patients with asthma, physicians should only prescribe Breo Ellipta for patients not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid, or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue Breo Ellipta) if possible without loss of asthma control and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use BREO ELLIPTA for patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids.
- Breo Ellipta is NOT indicated for the relief of acute bronchospasm.
Full US prescribing information, including BOXED WARNING and Medication Guide is available at us.gsk.com or US Prescribing Information for Breo Ellipta.
About Seretide Accuhaler (fluticasone propionate + salmeterol)
Seretide Accuhaler is a twice-daily dual combination treatment comprising fluticasone propionate /salmeterol, in the Accuhaler inhaler.
Seretide Accuhaler is indicated in Europe in the regular treatment of patients aged 4 and over with asthma, where use of a combination product (long-acting ß2–agonist, LABA, and inhaled corticosteroid, ICS) is appropriate: Patients not adequately controlled on both ICS and ‘as-needed’ short-acting ß2-agonist (SABA); Patients already adequately controlled on both ICS and LABA.
For the UK Summary of Product Characteristics (SmPC), please visit: https://www.medicines.org.uk/emc/medicine/2317/SPC/Seretide+100,+250,+500+Accuhaler
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. For further information please visit www.gsk.com.
RELVAR®, BREO®, ELLIPTA®,SERETIDE®, ACCUHALER®, ADVAIR®, DISKUS® are trademarks of the GlaxoSmithKline group of companies.
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®. In addition, Innoviva retains a 15 percent economic interest in future payments made by GSK for earlier-stage programs partnered with Theravance Biopharma, Inc., including the closed triple combination therapy for COPD. For more information, please visit Innoviva’s website at www.inva.com.
SOURCE: GlaxoSmithKline
Post Views: 102
LONDON, UK I February 23, 2017 I GlaxoSmithKline plc (LSE/NYSE:GSK) and Innoviva, Inc. (NASDAQ: INVA) today announced positive headline results from a non-inferiority lung function study, which demonstrated that patients with well-controlled asthma were able to switch to the once-daily Relvar® Ellipta® (fluticasone furoate/vilanterol, FF/VI) 100/25, an inhaled corticosteroid (ICS)/long-acting beta2 agonist (LABA) combination, from the twice-daily Seretide® Accuhaler® (fluticasone propionate /salmeterol, FP/SAL) 250/50, without compromising their lung function.
Patients randomised to FF/VI taken once-daily maintained lung function comparable with those randomised to the twice-daily FP/SAL [difference +19mL (95% CI: -11mL, +49mL], meeting the study’s primary endpoint, based on the lower bound (-11ml) of the 95% confidence interval falling above the non-inferiority margin of -100mL.
A third treatment arm with fluticasone propionate (FP), ICS monotherapy, was included to detect a lung function difference between treatments. Results demonstrated statistically significant differences in favour of the ICS/LABA combinations to FP (p<0.001).
The incidences of on-treatment serious adverse events (SAEs) and adverse events (AEs) of special interest were consistent with the known safety profile of FF/VI, established in asthma patients from other studies.
Eric Dube, SVP and Global Head of Respiratory Franchise, GSK said: At GSK we are constantly searching for ways in which we can help patients better manage their asthma. In this positive study we have demonstrated non-inferiority for once-daily Relvar versus twice-daily Seretide on lung function. This gives us confidence that for patients who struggle taking a twice-daily treatment regimen, there may be a once-daily treatment option available, providing greater physician choice to help patients.”
Mike Aguiar, CEO of Innoviva, Inc., added: “We believe the results of this study are important for patients and physicians. They provide additional evidence that patients with persistent asthma, who are currently treated with a twice-daily ICS/LABA, in this case Seretide, can experience a similar level of benefit in lung function when treated with Relvar Ellipta, which only needs to be taken once a day.”
The study design was agreed with European regulatory authorities. GSK now intends to submit this data to the European Medicines Agency (EMA).
Results from the study will be shared in future publications and presentations.
Study Design
Following a 4-week open-label treatment period with FP/SAL 250/50 twice-daily, patients with well controlled asthma were randomised to receive either FF/VI 100/25 once-daily, FP/SAL 250/50 twice-daily or FP 250 twice-daily in a double-blind, double-dummy manner for 24 weeks at multiple centres in 12 countries.
The primary objective of the study was to demonstrate non-inferiority of Relvar Ellipta 100/25 once-daily with Seretide Accuhaler 250/50 twice-daily in adult and adolescent subjects 12 years of age and older with persistent bronchial asthma, well controlled on twice-daily ICS/LABA. The endpoint for the study was the change from baseline in clinic visit evening FEV1 (pre-brochodilator and pre-dose) at the end of the 24-week treatment period.
To demonstrate the non inferiority of FF/VI vs FP/SAL the lower limit of the 95% confidence interval for the mean difference in change from baseline for evening FEV1 needed to be greater than the pre defined margin of -100mL. This was to rule out the possibility that FF/VI was more than -100mL inferior to FP/SAL.
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.
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 Relvar Ellipta (fluticasone furoate + vilanterol)
Relvar Ellipta is a once-daily dual combination treatment comprising fluticasone furoate, an inhaled corticosteroid and vilanterol, a long-acting beta2-agonist, in a single inhaler, the Ellipta®.
Relvar Ellipta is indicated in Europe in the regular treatment of patients aged 12 and over with asthma, where use of a combination product (long-acting ß2–agonist, LABA, and inhaled corticosteroid, ICS) is appropriate: Patients not adequately controlled on both ICS and ‘as-needed’ short-acting ß2-agonist (SABA).
Full EU prescribing information is available at: EU Prescribing Information for Relvar Ellipta.
Important safety information for Relvar Ellipta in Europe
FF/VI is contraindicated in patients with hypersensitivity to either fluticasone furoate, vilanterol, or any of the excipients.
FF/VI should not be used to treat acute asthma symptoms or an acute exacerbation in COPD, for which a short-acting bronchodilator is required. Increasing use of short-acting bronchodilators to relieve symptoms indicates deterioration of control and patients should be reviewed by a physician.
Patients should not stop therapy with FF/VI in asthma or COPD, without physician supervision since symptoms may recur after discontinuation.
Asthma-related adverse events and exacerbations may occur during treatment with FF/VI. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation of treatment with FF/VI.
Paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. This should be treated immediately with a short-acting inhaled bronchodilator. FF/VI should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary.
Cardiovascular effects, such as cardiac arrhythmias e.g. supraventricular tachycardia and extrasystoles may be seen with sympathomimetic medicinal products including FF/VI. Therefore fluticasone furoate/vilanterol should be used with caution in patients with severe cardiovascular disease.
For patients with moderate to severe hepatic impairment, the 92/22 mcg dose should be used and patients should be monitored for systemic corticosteroid-related adverse reactions. FF/VI 184/22 mcg is not indicated for patients with COPD. There is no additional benefit of the 184/22 mcg dose compared to the 92/22 mcg dose and there is a potential increased risk of pneumonia and systemic corticosteroid-related adverse reactions.
An increase in the incidence of pneumonia has been observed in subjects with COPD receiving FF/VI. There was also an increased incidence of pneumonias resulting in hospitalisation. In some instances these pneumonia events were fatal.
The incidence of pneumonia in patients with asthma was common at the higher dose. In a previous study of FF/VI in asthma the incidence of pneumonia in patients with asthma taking FF/VI 184/22 mcg was numerically higher compared with those receiving FF/VI 92/22 mcg or placebo.
Hyperglycaemia: There have been reports of increases in blood glucose levels in diabetic patients and this should be considered when prescribing to patients with a history of diabetes mellitus.
Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods. These effects are much less likely to occur than with oral corticosteroids. Possible systemic effects include Cushing’s syndrome, Cushingoid features, adrenal suppression, decrease in bone mineral density, growth retardation in children and adolescents, cataract and glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children).
FF/VI should be administered with caution in patients with pulmonary tuberculosis or in patients with chronic or untreated infections. Data from large asthma and COPD clinical trials were used to determine the frequency of adverse reactions associated with FF/VI.
Very common adverse reactions (occurring in >1/10 patients) with FF/VI were headache and nasopharyngitis. Common adverse reactions (occurring in >1/100 to <1/10 patients) were pneumonia, upper respiratory tract infection, bronchitis, influenza, candidiasis of mouth and throat, oropharyngeal pain, sinusitis, pharyngitis, rhinitis, cough, dysphonia, abdominal pain, arthralgia, back pain, fractures, and pyrexia and muscle spasms..Extrasystoles were observed as an uncommon adverse reaction (occurring in >1/1,000 to <1/100 patients). Rare adverse reactions (occurring in >1/10,000 to < 1/1,000) were hypersensitivity reactions (including anaphylaxis, angioedema, rash and urticaria), anxiety, tremor, palpitations, tachycardia and paradoxical bronchospasm. With the exception of pneumonia and fractures, the safety profile was similar in patients with asthma and COPD. During clinical studies, pneumonia and fractures were more frequently observed in patients with COPD.
Relvar Ellipta is known as Breo Ellipta in the United States. Breo Ellipta is licensed in the US for:
- The once-daily treatment of asthma in patients aged 18 years and older.
Long-acting beta2-adrenergic agonists (LABA), such as vilanterol, one of the active ingredients in Breo Ellipta, increase the risk of asthma-related death. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients. Therefore, when treating patients with asthma, physicians should only prescribe Breo Ellipta for patients not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid, or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue Breo Ellipta) if possible without loss of asthma control and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use BREO ELLIPTA for patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids.
- Breo Ellipta is NOT indicated for the relief of acute bronchospasm.
Full US prescribing information, including BOXED WARNING and Medication Guide is available at us.gsk.com or US Prescribing Information for Breo Ellipta.
About Seretide Accuhaler (fluticasone propionate + salmeterol)
Seretide Accuhaler is a twice-daily dual combination treatment comprising fluticasone propionate /salmeterol, in the Accuhaler inhaler.
Seretide Accuhaler is indicated in Europe in the regular treatment of patients aged 4 and over with asthma, where use of a combination product (long-acting ß2–agonist, LABA, and inhaled corticosteroid, ICS) is appropriate: Patients not adequately controlled on both ICS and ‘as-needed’ short-acting ß2-agonist (SABA); Patients already adequately controlled on both ICS and LABA.
For the UK Summary of Product Characteristics (SmPC), please visit: https://www.medicines.org.uk/emc/medicine/2317/SPC/Seretide+100,+250,+500+Accuhaler
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. For further information please visit www.gsk.com.
RELVAR®, BREO®, ELLIPTA®,SERETIDE®, ACCUHALER®, ADVAIR®, DISKUS® are trademarks of the GlaxoSmithKline group of companies.
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®. In addition, Innoviva retains a 15 percent economic interest in future payments made by GSK for earlier-stage programs partnered with Theravance Biopharma, Inc., including the closed triple combination therapy for COPD. For more information, please visit Innoviva’s website at www.inva.com.
SOURCE: GlaxoSmithKline
Post Views: 102
