Commissioning Support Glycopyrronium bromide ®▼ (Seebri Breezhaler )

For maintenance treatment of COPD

Commissioning guidance: Commissioners may wish to bear the following in mind when considering the commissioning of glycopyrronium bromide:  Based on the published evidence, glycopyrronium bromide appears to be of similar efficacy to tiotropium but longer term data are lacking.  Based on current prices, glycopyrronium bromide is less expensive than tiotropium.  Glycopyrronium bromide could be considered as an option when initiating treatment for a new patient.  There is insufficient evidence to support a switch in prescribing from tiotropium to glycopyrronium bromide in patients already receiving treatment for chronic obstructive pulmonary disease (COPD).  The patent for tiotropium is expected to expire in 2015.  Commissioners may also wish to consider the prescribing of glycopyrronium and tiotropium within the context of the development of an overall care pathway for COPD treatment in the West Midlands.

Prescribing guidance: Category A (Q3) BNF: 3.1.2 Glycopyrronium bromide is suitable for prescribing in primary care for the maintenance treatment of chronic

obstructive pulmonary disease (COPD).

Q3 rating: The evidence for the efficacy of glycopyrronium bromide was Q2 Q1 considered to be relatively strong. Two randomised controlled trials found higher place higher place that it was more effective than placebo in improving lung function, weaker evidence stronger evidence breathlessness and lowering exacerbations. In the GLOW 1 trial, there were significantly fewer hospitalisations due to an exacerbation of COPD than in placebo-treated patients. After 52 weeks’ treatment, there was no Q4 Q3 statistically significant difference in FEV1 values for glycopyrronium in lower place lower place comparison with an open-label tiotropium reference arm. It has a lower weaker evidence stronger evidence

place in therapy because longer term evidence for efficacy (over 52 Placein therapy in primary care weeks) is not yet available. Strength of evidence for efficacy The Q rating relates to the drug’s position on the effectiveness indicator grid. The strength of the evidence is determined by the quality and quantity of studies that show significant efficacy of the drug compared with placebo or alternative therapy. Its place in therapy in primary care takes into account safety and practical aspects of using the drug in primary care, alternative options, relevant NICE guidance, and the need for secondary care input.

Description of technology emergency hospital admissions in the West 4 Glycopyrronium bromide is an inhaled long-acting Midlands. muscarinic receptor antagonist (LAMA). It is licensed Clinical evidence for efficacy and safety as a maintenance bronchodilator treatment to relieve 1 Three phase 3, randomised controlled trials (RCTs) symptoms in adult patients with COPD. The with similar inclusion and exclusion criteria evaluated recommended dose is the inhalation of one capsule once-daily glycopyrronium bromide (50 mcg) in 1,996 per day from a low resistance single dose dry powder patients with moderate to severe COPD. The GLOW inhaler (Breezhaler; delivered dose of glycopyrronium 5 6 1 1 and GLOW 2 trials were double-blind, placebo- 44 µg). controlled trials that evaluated glycopyrronium over 26 Background and 52 weeks respectively, and measured lung function (trough FEV [Forced Expiratory Volume in COPD is an inflammatory disease characterised by 1 one second]), breathlessness (TDI focal score pulmonary airflow obstruction that is usually [Transition Dyspnoea Index]) and quality of life progressive and not fully reversible. COPD is a (SGRQ [St George’s Respiratory Questionnaire]). common cause of long-term disability and death that The GLOW 2 trial also included an open-label presents a major burden to healthcare services. tiotropium (18 mcg once daily) treatment arm.6 There are estimated to be over 3 million people with 7 2 GLOW 3 was a short, 21-day placebo-controlled COPD in the UK. Quality and outcomes framework crossover trial that evaluated the efficacy of (QOF) data for 2011/12 show that the diagnosed glycopyrronium (50 mcg once daily) in improving prevalence of COPD in the West Midlands is 1.7% 3 exercise tolerance in patients with moderate to severe (99,000 patients). Between April 2010 and March COPD. 2011, COPD was the primary diagnosis in 31,795

November 2012 Page 1 of 2 In the GLOW 1 and 2 trials, morning and evening daily glycopyrronium-treated patients compared with clinical symptoms and rescue medication use were placebo-treated patients (1.7% vs. 4.2%, ARD = recorded in an electronic patient diary. Exacerbations 2.5%, NNT = 40; p = 0.024). were also recorded. In all three trials, concomitant Exercise endurance: In the GLOW 3 trial,7 after 21 medications (inhaled corticosteroids [ICS], intranasal days’ treatment, the mean exercise endurance was corticosteroids, or H1 antagonists) were permitted in 506 seconds in glycopyrronium-treated patients patients who had been stabilised on a recommended (8.5 minutes) compared with 417 seconds (7 minutes) and constant dose prior to study entry. in placebo-treated patients (~ 21% difference, FEV1 (lung function): After 12 weeks’ treatment, in p < 0.001). the GLOW 1 and 2 trials, trough (pre-dose) FEV 1 Adverse events values were higher with glycopyrronium treatment than placebo (treatment differences of 108 mL and According to the EMA assessment report for 97 mL for GLOW 1 and 2 respectively, p < 0.001).5,6 glycopyrronium,8 there were about 2,300 patients In GLOW 2, the FEV1 for the tiotropium reference arm exposed to glycopyrronium for a total of about 773 was also higher than placebo (treatment difference patient-years. The most frequently reported adverse 83 mL, p < 0.001). In the GLOW 2 trial, there was no event was worsening of COPD, which was reported in significant difference in trough FEV1 between 27 to 43% of placebo-treated patients, 20 to 36% of glycopyrronium and tiotropium for the primary glycopyrronium-treated patients and in 34% of outcome at week 12, or at study end at week 52.6 tiotropium-treated patients. Other frequently reported Breathlessness (TDI focal score): In GLOW 1 and adverse events were upper respiratory tract infection (URTI), nasopharyngitis, cough, bacterial URTI, and 2, after 26 weeks’ treatment, glycopyrronium had 5,6,8 improved TDI focal scores significantly more than headache. These events were all reported to be of placebo. In the GLOW 1 trial, the treatment difference lesser frequency in the glycopyrronium group than in of 1.04 points for glycopyrronium vs. placebo was placebo-treated patients. Adverse events associated clinically significant (minimally clinically important with anticholinergic treatment were dry mouth, difference [MCID] ≥ 1 point). The treatment constipation and blurred vision. differences vs. placebo in the GLOW 2 trial were not Considerations for cost impact clinically significant (0.81 and 0.94 for glycopyrronium and tiotropium respectively). Sixty-one percent and  At current prices, the cost of a year’s treatment 55% of glycopyrronium-treated patients in GLOW 1 with glycopyrronium bromide once daily inhalation and 2 respectively achieved the MCID, compared with is £335. 48% and 44% of placebo-treated patients, and 53% of References tiotropium-treated patients (in GLOW 2). 1. Novartis Pharmaceuticals UK Ltd. Seebri Breezhaler Quality of life (SGRQ): In both trials, patients Inhalation Powder, Hard capsules 44 mcg. EMC. 2012. receiving glycopyrronium treatment had significantly http://www.medicines.org.uk/EMC/medicine/27138/SPC/Se lower (better) SGRQ scores than placebo (p = 0.004). ebri+Breezhaler+Inhalation+Powder%2c+Hard+Capsules+4 Mean treatment differences for glycopyrronium 4mcg/ compared with placebo did not reach the threshold for 2. Roflumilast for severe COPD? DTB 2011;49:45-8. 3. The Quality and Outcomes Framework 2011/12. NHS clinical significance (MCID ≥ 4 point reduction). In Information Centre. 2012. http://www.ic.nhs.uk/statistics- GLOW 1, 56.8% in the glycopyrronium group and-data-collections/audits-and-performance/the-quality- achieved the MCID vs. 46.3% in the placebo group. and-outcomes-framework In GLOW 2, 54.3% in the glycopyrronium group 4. Hospital episode statistics data. HESonline. 2012. achieved the MCID, compared with 59.4% in the http://www.hesonline.nhs.uk/Ease/servlet/ContentServer?sit tiotropium group and 50.8% of patients in the placebo eID=1937 5. D'Urzo A et al. Efficacy and safety of once-daily NVA237 in group (p = not reported). patients with moderate-to-severe COPD: the GLOW1 trial. Exacerbations: During the 26-week GLOW 1 trial, Respir Res 2011;12:156. 17.5% of glycopyrronium-treated patients had one or 6. Kerwin E et al. Efficacy and safety of NVA237 versus more moderate to severe exacerbations, compared placebo and tiotropium in patients with moderate-to-severe COPD over 52 weeks: The GLOW2 study. Eur Respir J with 24% of placebo-treated patients (p = not 2012. reported). In the 52-week GLOW 2 trial, the European 7. Beeh KM et al. Once-daily NVA237 improves exercise 8 Medicines Agency (EMA) assessment report showed tolerance from the first dose in patients with COPD: the that 33% and 30% of glycopyrronium and tiotropium- GLOW3 trial. Int J Chron Obstruct Pulmon Dis 2012;7:503- treated patients, respectively, had a moderate to 13. severe exacerbation, compared with 40% of placebo- 8. Seebri Breezhaler. EMA. 2012. http://www.ema. europa.eu/ema/index.jsp?curl=pages/medicines/human/me treated patients (p = not reported). dicines/002430/smops/Positive/human_smop_000390.jsp& In the GLOW 1 trial there were significantly fewer mid=WC0b01ac058001d127&jsenabled=true hospitalisations due to an exacerbation of COPD in

Launch date: November 2012 Manufacturer: Novartis WARNING: This sheet should be read in conjunction with the Summary of Product Characteristics This guidance is based upon the published information available in English at the time the drug was considered. It remains open to review in the event of significant new evidence emerging. MTRAC can be contacted at Medicines Management, School of Pharmacy, Keele University, Keele, Staffordshire ST5 5BG Tel: 01782 734131 Fax: 01782 713586 Email: [email protected] Web: www.mtrac.co.uk NICE GUIDANCE ON GLYCOPYRRONIUM WAS NOT AVAILABLE AT TIME OF PUBLICATION OF THIS COMMISSIONING SUPPORT SHEET Date: November 2012 ©Midlands Therapeutics Review & Advisory Committee