Incruse Ellipta 55mcg (umeclidinium bromide) for the relief of symptoms in adult patients with Chronic Obstructive Pulmonary Disease (COPD):

Transcription

1 Incruse Ellipta 55mcg (umeclidinium bromide) for the relief of symptoms in adult patients with Chronic Obstructive Pulmonary Disease (COPD): An introduction for Clinical Commisioning Groups and Health Boards BRAND NAME GENERIC NAME LICENSED INDICATION THERAPEUTIC CLASS ANTICIPATED PLACE IN THERAPY DOSAGE Incruse Ellipta Umeclidinium bromide Maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD) Incruse Ellipta is a long acting muscarinic receptor antagonist (also referred to as an anticholinergic or LAMA). Where LAMAs are currently positioned within UK guidelines for the treatment of patients with COPD, either as monotherapy or triple therapy with an ICS/LABA Incruse Ellipta 55 micrograms inhalation powder (delivered dose). This corresponds to a pre-dispensed dose of Incruse 62.5 micrograms The recommended dose in adults (also the maximum dose) is one inhalation of Incruse Ellipta once daily at the same time of the day each day. ADMINISTRATION Inhaled via an Ellipta multi-dose dry powder inhaler COST The 30-day cost of Incruse Ellipta is REGULATORY STATUS Marketing Authorisation was received on 28th April 2014 Prescribing Information can be found at the end of this document.

2 Clinical efficacy 1-3 Incruse was evaluated in 904 adult patients who received umeclidinium bromide or placebo from two Phase III clinical studies with a clinical diagnosis of COPD; a 12-week study 2 and a 24-week study. 3 These were both randomised, double-blind, parallel group, placebo-controlled studies. Synopsis of Incruse studies 12-WEEK STUDY 2 24-WEEK STUDY 3 12-week treatment period (84 days) 69 subjects in the umeclidinium 55mcg once-daily treatment arm vs 68 subjects in the placebo arm Primary endpoint: Trough FEV 1 on day 85 Key secondary end-points: Weighted mean (wm) FEV h post-dose on days 1, 28 and 84, and serial FEV 1 at 1, 3, 6, 23 and 24 h post-dose on days 1 and week treatment period (168 days) 418 subjects in the umeclidinium 55mcg once-daily treatment arm vs 280 subjects in the placebo arm Primary Efficacy Endpoint: Trough FEV 1 on Day 169 Key secondary end-points: Weighted mean (wm) FEV h post-dose on days 168 and trough and 0-6 h wm FEV 1 at other visits, serial FEV 1 assessments Results Incruse has demonstrated statistically significant and clinically meaningful improvements in lung function compared with placebo after the first day of treatment which were maintained over the 12-week and 24-week treatment periods. 1 INCRUSE 12-WEEK STUDY 2 INCRUSE 24-WEEK STUDY 3 Trough FEV 1 on Day 85 with Umec 55mcg (n=69) Trough FEV 1 on Day 169 with Umec 55 mcg (n=418) Difference vs placebo (ml) 127 Difference vs placebo (ml) % CI (52,202) 95% CI (76,155) p-value <0.001 p-value <0.001 Figure 1 2 : Change from baseline in trough forced expiratory volume in 1 s (FEV 1 ). Adapted from Trivedi et al., Figure 2 3 : Change from baseline in trough forced expiratory volume in 1 s (FEV 1 ). Adapted from J.F. Donahue et al., Change in trough FEV1 from baseline (ml) Placebo Umec 55mcg LS mean (95% Cl) change from baseline (ml) Placebo Umec 55 mcg Time (days) Time (days) All data are presented as least square means with 95% confidence intervals.

3 Incruse Ellipta demonstrated clinically meaningful improvements 4 in breathlessness (TDI focal score) compared to placebo over 12 weeks (1.0 unit, p=ns) 2 and 24 weeks (1.0 unit, p<0.001) 3, although the improvement seen in the 12 week study was not statistically significant. Incruse also demonstrated an improvement in health-related quality of life measured using the St. George s Respiratory Questionnaire (SGRQ); (12 week study: units, p<0.001; 24 week study: units, p=ns*). 1-3 In the 24 week study, Incruse lowered the risk of a COPD exacerbation compared with placebo (8.9% vs 13.7%; hazard ratio 0.6). 3 * This study was not specifically designed to evaluate the effects of treatments on COPD exacerbations. * A step-down statistical testing procedure was used in this study and this comparison was below a comparison that did not achieve statistical significance. Therefore, statistical significance on this comparison cannot be inferred. Incruse Ellipta in combination with Relvar Ellipta (vilanterol/fluticasone furoate) 92/22 mcg has demonstrated statistically significant and clinically meaningful improvements in lung function compared with placebo in combination with Relvar Ellipta 92/22 mcg 5,6 In two similar Phase III studies, adding Incruse Ellipta to Relvar Ellipta 92/22mcg demonstrated (compared to placebo in combination with Relvar Ellipta 92/22mcg): statistically significant improvements in lung function (trough FEV 1 ) in both studies at week 12 (124mL, p<0.001; 122mL, p<0.001) 5,6 statistically significant reduction in rescue salbutamol use in both studies over 12 weeks (0.4 puffs per day, p<0.001; 0.3 puffs per day, p=0.003) 5,6 improvements in health-related quality of life scores (as measured by SGRQ) at week 12 (-0.82 units, p=ns; units, p=0.011) 5,6, although the reduction seen in one of the studies was not statistically significant Relvar Ellipta is licensed for the symptomatic treatment of adults with COPD with a FEV 1 <70% predicted normal (post-bronchodilator) and an exacerbation history despite regular bronchodilator therapy 11 Safety profile of Incruse Ellipta 1 The safety profile of Incruse was evaluated from 1663 patients with COPD who received doses of 55 micrograms or greater for up to one year. This includes 576 patients who received the recommended dose of 55 micrograms once daily. The most frequently reported adverse reactions with Incruse were nasopharyngitis and upper respiratory tract infection. SYSTEM ORGAN CLASS ADVERSE REACTIONS FREQUENCY Infections and infestations Nasopharyngitis Upper respiratory tract infection Urinary tract infection Sinusitis Pharyngitis Infections and infestations Headache Cardiac disorders Tachycardia Atrial fibrillation Rhythm idioventricular Supraventricular tachycardia Supraventricular extrasystoles Respiratory, thoracic and mediastinal disorders Cough Gastrointestinal disorders Constipation Dry mouth Skin and subcutaneous tissue disorders Rash

4 Safety profile of Relvar Ellipta in COPD In the COPD clinical development programme a total of 6,237 subjects were included in an integrated assessment of adverse reactions. The most commonly reported adverse reactions with fluticasone furoate and vilanterol were headache and nasopharyngitis. 11 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 commonly observed in patients with COPD The risk of pneumonia in COPD with Relvar 92/22 mcg is similar to that reported for other ICS/LABAs within independent Cochrane meta-analysis. 11,12,13 - Pneumonia occurred in 6% of patients on Relvar Ellipta 92/22 mcg compared with 3% of patients receiving vilanterol 22 mcg alone The number of pneumonia events per 1000 patient years was 85.7 with Relvar Ellipta 92/22 mcg and 42.3 with vilanterol 22 mcg. 11 Ellipta inhaler 1 Incruse is delivered in the Ellipta inhaler. Straightforward to use 7 and is preferred vs. HandiHaler with regard to the number of steps to use, time taken to use and overall preference for the inhaler. 8 Patients reported high levels of satisfaction with and a very positive experience of using the Ellipta inhaler. 7 Drivers of patient preference when using the Ellipta inhaler have shown to be: ease of handling; size; portability and storage; the shape of the mouthpiece and seal made with the lips on inhalation; and the size and visibility of the dose counter. 7 Cost LAMA 30-DAY COST 9 LAMA & ICS/LABA 30-DAY COST 9 Incruse Ellipta 55 mcg Seebri Breezhaler (glycopyrronium bromide) 50 mcg Eklira Genuair (aclidinium bromide) 322 mcg Spiriva Handihaler (tiotropium bromide) 18 mcg Spiriva Respimat (tiotropium bromide) 2.5 mcg Incruse Ellipta 55 mcg & Relvar Ellipta (vilanterol/ fluticasone furoate) 92/22 mcg Spiriva * Handihaler 18mcg & Seretide ** Accuhaler 500/50 mcg *most prescribed LAMA 10 **most prescribed ICS/LABA GSK s respiratory portfolio and the role of Incruse GSK have developed a portfolio of respiratory medicines to help meet the needs of patients and healthcare professionals. Incruse Ellipta is an effective 2,3 once-daily LAMA 1 which completes our current COPD portfolio of inhaled medicines. Incruse Ellipta is an option for delivering single bronchodilation for breathless patients needing a LAMA. Combining Incruse with Relvar as part of triple therapy provides patients with the first once-daily triple-therapy combination 1,11, delivered through the same straightforward and patient-preferred Ellipta inhaler 4,5, (one Incruse Ellipta inhaler and one Relvar Ellipta inhaler), with potential cost-savings for the NHS 9.

5 References: 1. Incruse Ellipta Summary of Product Characteristics; accessed January Roopa Trivedi, Nathalie Richard, Rashmi Mehta, Alison Church. Umeclidinium in patients with COPD: a randomised, placebo-controlled study. European Respiratory Journal 2014; 43: J. F. Donohue, M. R. Maleki-Yazdi, S. Kilbride, R. Mehta, C. Kalberg, A. Church. Efficacy and safety of once-daily umeclidinium/vilanterol 62.5/25 mcg in COPD. Respiratory Medicine 2014; 107: Mahler DA, Witek TJ, Jr. The MCID of the transition dyspnea index is a total score of one unit. COPD 2005; 2(1): Data on file UK/INC/0009/ Data on file UK/INC/0015/ Hendrik Svedsater, Peter Dale, Karl Garrill, Richard Walker, Mark W Woepse. Qualitative assessment of attributes and ease of use of the ELLIPTA dry powder inhaler for delivery of maintenance therapy for asthma and COPD. BMC Pulmonary Medicine 2013; 13(72). 8. J H Riley, M M Tabberer, N Richard, A C Donald, A Church, S S Harris. Use of a new dry powder inhaler to deliver umeclidinium/vilanterol in the treatment of COPD: Annual Congress of the European Respiratory Society (ERS) 2013; poster P emims; LAMA and ICS/LABA prices; accessed January CSD Patient Data, Cegedim Strategic Data Ltd, MAT May Relvar Ellipta 92/22mcg Summary of Product Characteristics; accessed January Kew et al. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease. Cochrane Database Syst.Rev. 2014; 3:CD Nannini et al. Combined corticosteroid and long-acting beta 2 -agonist in one inhaler versus long-acting beta 2 -agonists for chronic obstructive pulmonary disease. Cochrane Database Syst.Rev.2012; 9:CD Dransfield MT et al. A once-daily inhaled coricosteroid, long-acting beta 2 -agonist combination, fluticasone furoate (FF)/vilanterol (VI), for the prevention of COPD exacerbations. Lancet Resp Med 2013; 1(3): Prescribing information Incruse Ellipta (umeclidinium bromide) (Please consult the full Summary of Product Characteristics (SmPC) before prescribing) Incruse Ellipta 55 (umeclidinium) inhalation powder. Each single inhalation provides a delivered dose (the dose leaving the mouthpiece of the inhaler) of 55 micrograms umeclidinium (equivalent to 65 micrograms of umeclidinium bromide). This corresponds to a pre-dispensed dose of 62.5 micrograms umeclidinium equivalent to 74.2 micrograms umeclidinium bromide. Indications: COPD: Maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD). Dosage and administration: Inhalation only. COPD: One inhalation once daily of Incruse Ellipta at the same time of the day each day. Contraindications: Hypersensitivity to the active substances or to any of the excipients (lactose monohydrate and magnesium stearate). Precautions: Incruse Ellipta should not be used in patients with asthma. Treatment with Incruse Ellipta should be discontinued in the event of paradoxical bronchospasm and alternative therapy initiated if necessary. Cardiovascular effects may be seen after the administration of muscarinic receptor antagonists, therefore Incruse Ellipta should be used with caution in patients with severe cardiovascular disorders, particularly cardiac arrhythmias. Incruse Ellipta should be used with caution in patients with urinary retention or narrow angle glaucoma. No dosage adjustment is required in renal or mild to moderate hepatic impairment. Acute symptoms: Incruse Ellipta is not indicated for acute episodes of bronchospasm. Warn patients to seek medical advice if short-acting inhaled bronchodilator use increases, a re-evaluation of the patient and of the COPD treatment regimen should be undertaken. Interactions with other medicinal products: Coadministration of umeclidinium bromide with other long-acting muscarinic antagonists or medicinal products containing this active substance has not been studied and therefore, is not recommended. Fertility, pregnancy, and breast-feeding: No available human invivo data. Balance risks against benefits. Side effects: : nasopharyngitis, upper respiratory tract infection, headache, urinary tract infection sinusitis, tachycardia and cough. : pharyngitis, atrial fibrillation, rhythm idioventricular, supraventricular tachycardia, supraventricular extrasystoles, rash, dry mouth and constipation. Legal category: POM. Presentation and Basic NHS cost: Incruse Ellipta. 1 inhaler x 30 doses. Incruse Ellipta Marketing authorisation (MA) nos. 55mcg 1x30 doses [EU/1/14/922/002]; MA holder: Glaxo Group Ltd, 980 Great West Road, Brentford, Middlesex TW8 9GS, UK. Last date of revision: December UK/RESP/0122/14(2). Incruse and Ellipta are registered trademarks of the GlaxoSmithKline group of companies. All rights reserved. Adverse events should be reported. Reporting forms and information can be found at Adverse events should also be reported to GlaxoSmithKline on Prescribing information Relvar Ellipta (fluticasone furoate/vilanterol [as trifenatate]) (Please consult the full Summary of Product Characteristics (SmPC) before prescribing) Relvar Ellipta (fluticasone furoate/vilanterol [as trifenatate]) inhalation powder. Each single inhalation of fluticasone furoate (FF) 100 micrograms (mcg) and vilanterol (VI) 25mcg provides a delivered dose of 92mcg FF and 22mcg VI. Each single inhalation of FF 200mcg and VI 25mcg provides a delivered dose of 184mcg of FF and 22mcg of VI. Indications: Asthma: Regular treatment of asthma in patients 12 years and older not adequately controlled on inhaled corticosteroids and as needed short-acting inhaled β 2 -agonists, where a long-acting β 2 -agonist and inhaled corticosteroid combination is appropriate. COPD: Symptomatic treatment of adults with COPD with a FEV 1 <70% predicted normal (post-bronchodilator) and an exacerbation history despite regular bronchodilator therapy. Dosage and administration: Inhalation only. Asthma: Adults and adolescents 12 years: one inhalation once daily of: Relvar 92/22mcg for patients who require a low to mid dose of inhaled corticosteroid in combination with a long-acting β 2 -agonist. If patients are inadequately controlled then the dose can be increased to one inhalation once daily Relvar 184/22mcg. Relvar 184/22mcg can also be considered for patients who require a higher dose of inhaled corticosteroid in combination with a long-acting β 2 -agonist. Regularly review patients and reduce dose to lowest that maintains effective symptom control. COPD: one inhalation once daily of Relvar 92/22mcg. Contraindications: Hypersensitivity to the active substances or to any of the excipients (lactose monohydrate & magnesium stearate). Precautions: Pulmonary tuberculosis, severe cardiovascular disorders, chronic or untreated infections, diabetes mellitus. Paradoxical bronchospasm substitute alternative therapy if necessary. In patients with hepatic with moderate to severe impairment 92/22mcg dose should be used. Acute symptoms: Not for acute symptoms, use short-acting inhaled bronchodilator. Warn patients to seek medical advice if short-acting inhaled bronchodilator use increases. Therapy should not be abruptly stopped without physician supervision due to risk of symptom recurrence. Asthma-related adverse events and exacerbations may occur during treatment. Patients should continue treatment but seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation of Relvar. Systemic effects: Systemic effects of inhaled corticosteroids may occur, particularly at high doses for long periods, but much less likely 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, glaucoma. More rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). Increased incidence of pneumonia has been observed in patients with COPD receiving Relvar. Risk factors for pneumonia include: current smokers, patients with a history of prior pneumonia, patients with a body mass index <25 kg/m 2 and patients with a FEV 1 <50% predicted. If pneumonia occurs with Relvar treatment should be re-evaluated. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take Relvar. Interactions with other medicinal products: Interaction studies have only been performed in adults. Avoid β-blockers. Caution is advised when co-administering with strong CYP 3A4 inhibitors (e.g. ketoconazole, ritonavir). Concomitant administration of other sympathomimetic medicinal products may potentiate the adverse reactions of FF/VI. Relvar should not be used in conjunction with other long-acting β 2 -adrenergic agonists or medicinal products containing long-acting β 2 -adrenergic agonists. Pregnancy and breast-feeding: Experience limited. Balance risks against benefits. Side effects: Very ( 1/10): Headache, nasopharyngitis. ( 1/100 to <1/10): Candidiasis of the mouth and throat, dysphonia, pneumonia, bronchitis, upper respiratory tract infection, influenza, oropharyngeal pain, sinusitis, pharyngitis, rhinitis, cough, abdominal pain, arthralgia, back pain, fractures, pyrexia. ( 1/1,000 to <1/100): Extrasystoles. Rare ( 1/10,000 to <1/1,000); Hypersensitivity reactions including anaphylaxis, angioedema, rash, and urticaria. Legal category: POM. Presentation and Basic NHS cost: Relvar Ellipta. 1 inhaler x 30 doses. Relvar Ellipta 92/ Relvar Ellipta 184/ Marketing authorisation (MA) nos. 92/22mcg 1x30 doses [EU/1/13/886/002]; 184/22mcg 1x30 doses [EU/1/13/886/005]. MA holder: Glaxo Group Ltd, 980 Great West Road, Brentford, Middlesex TW8 9GS, UK. Last date of revision: December UK/RESP/0332/14. Relvar and Ellipta are registered trademarks of the GlaxoSmithKline group of companies. All rights reserved. Relvar Ellipta was developed in collaboration with Theravance, Inc. Adverse events should be reported. Reporting forms and information can be found at Adverse events should also be reported to GlaxoSmithKline on Seretide and Accuhaler are registered trademarks of the GlaxoSmithKline group of companies. Seebri and Breezhaler are registered trademarks of Novartis Pharmaceuticals. Eklira and Genuair are registered trademarks of Almirall. Spiriva, Handihaler and Respimat are registered trademarks of Boehringer Ingelheim Pharma. RELVAR ELLIPTA was developed in collaboration with 2014 GSK group of companies. All Rights Reserved.