/formoterol fumarate 12 g compared to Aclidinium bromide 400 g in - PowerPoint PPT Presentation

Assessing the cost-effectiveness of using Aclidinium bromide 400 µg /formoterol fumarate 12 µg compared to Aclidinium bromide 400 µg in the management of moderate to severe chronic obstructive pulmonary disease Ramos M, Haughney J, Henry N, Lindner L, Lamotte M IMS Health CE4 ISPOR Milan 2015 Monday, 9 November 2015 0

Disclosure on conflict of interest • IMS Health, the employer MR, NH and ML received consulting fees from Almirall/AstraZeneca for the development of the model and the preparation of this presentation. • JH received consulting fees for advising on the building of the model and information on the treatment of COPD in Scotland. • LL is a full time employee of AstraZeneca. Assessing the cost-effectiveness of using aclidinium 400µg / formoterol 12µg compared to aclidinium 400µg 1 in the management of COPD

Background • Aclidinium bromide/formoterol fumarate combines two effective inhaled bronchodilators with complementary mechanisms of action • Aclidinium bromide 400µg (a long-acting muscarinic antagonist - LAMA) • Formoterol fumarate 12µg (a long-acting beta-adrenergic agonist - LABA) • 2 phase III studies ACLIFORM and AUGMENT demonstrated that aclidinium/formoterol compared to aclidinium alone • Lung function capacity: increase in peak FEV1 values vs. placebo • aclidinium/formoterol: 293.2mL • aclidinium alone: 175.0mL • COPD-related symptoms FEV1 - mean baseline forced expiratory volume in one second Assessing the cost-effectiveness of using aclidinium 400µg / formoterol 12µg compared to aclidinium 400µg 2 in the management of COPD

Objective • To assess the cost-effectiveness of aclidinium/formoterol, against the LAMA, aclidinium alone in the management of COPD patients • Setting: Scotland Assessing the cost-effectiveness of using aclidinium 400µg / formoterol 12µg compared to aclidinium 400µg 3 in the management of COPD

The key design elements of this cost-effectiveness analysis Type of model A state-transition (Markov) developed in MS Excel Time horizon 5 years Cycle length 1 month Perspective NHS Scotland Comparator Aclidinium Patients COPD patients in moderate or severe health states Health states Severity levels defined by GOLD 2010 criteria Utility, resource use, cost and risk of exacerbation are health state specific COPD event Exacerbation • Mild - treated in community care • Severe - treated in hospital Pneumonia (rates differ by treatment option). Clinical data Published literature including pooled analysis on ACLIFORM and AUGMENT Cost data Year 2014 Published literature and local sources Costs and effects – 3.5% Discounting Outcome Cost per quality of life gained (QALY) GOLD-Global Initiative for Chronic Obstructive Lung Disease Assessing the cost-effectiveness of using aclidinium 400µg / formoterol 12µg compared to aclidinium 400µg in the 4 management of COPD

Markov Engine: Determining patient’s initial lung function capacity per health state • Initial distribution of patients by health state  59% moderate and 41% severe (ACLIFORM and AUGMENT) • To estimate the average FEV 1 of a mean patient of both ACLIFORM and AUGMENT trials, the Langhammer A. et. al. 2001 equations were used      2 FEV 1 exp( 9 . 091 2 . 004 ln( Height ) 0 . 000163 Age 0 . 007237 Age ) female  average age of patients (ACLIFORM and  2 . 476 liters AUGMENT)     2 FEV 1 exp( 10 . 556 2 . 342 ln( Height ) 0 . 0000685 Age ) males  average height of individuals in Scotland (Health  3 . 539 liters Survey for England, 2009) To estimate it per health state , the midpoint between the limits of the GOLD criteria was used as multiplicator to determine the severity level (in green/next slide) Post- bronchodilator FEV1 % of predicted normal value of the limits, midpoint of Estimated baseline FEV1 by gender and GOLD criteria health state (in Liters) COPD health states Minimum Maximum Midpoint Female Male Moderate 50% 80% 65.0% 1.61 2.30 Severe 30% 50% 40.0% 0.99 1.42 Very severe 0% 30% 15.0% 0.37 0.53 FEV1 - mean baseline forced expiratory volume in one second GOLD-Global Initiative for Chronic Obstructive Lung Disease Assessing the cost-effectiveness of using aclidinium 400µg / formoterol 12µg compared to aclidinium 400µg 5 in the management of COPD

Markov engine: simulating the progression of lung function capacity over time and the impact of the different therapies Key driver of the model: initial improvement in FEV1 due to treatment effect followed by decline over time • In the first 24 weeks: a linear improvement of FEV 1 due to treatment effect  Transitions will be from: .  moderate to mild .  severe to moderate . . . .  very severe to severe . . • After 24 weeks: only the natural evolution of COPD is . Time difference considered . .  lung function capacity declines by 41 ml per year (Tashkin . et al. 2008)  Transitions will be from:  mild to moderate  moderate to severe  severe to very severe • The most efficacious treatments will have a higher initial increase in FEV 1 and a delayed progression compared to less effective treatments • The best therapy will require more time to reach the next health state FEV1 - mean baseline forced expiratory volume in one second Assessing the cost-effectiveness of using aclidinium 400µg / formoterol 12µg compared to aclidinium 400µg 6 in the management of COPD

Initial increase in FEV1 in the two treatment arms • ACLIFORM and AUGMENT (= pooled analysis) • FDC 400/12µg statistically significantly improved lung function and breathlessness over 24 weeks compared with monotherapies  Lung function improvement was given by the increase of mean baseline forced expiratory volume in one second (FEV1) at 24 weeks and taken in the morning one-hour post-dose (as peak value) Mean difference in peak FEV1 by treatment at 24 24 weeks 4 weeks weeks (in ml) Type of bronchodilator Mean 95 CI Mean 95%CI LAMA+ LABA Aclidinium/formoterol 293.20 (265.00;321,00) 53.1 (48.0;58.2) LAMA alone Aclidinium 175.00 (147.00;203.00) 31.7 (26.6;36.8) OWSA: CI; PSA: Normal distributions. FEV1 - mean baseline forced expiratory volume in one second Assessing the cost-effectiveness of using aclidinium 400µg / formoterol 12µg compared to aclidinium 400µg 7 in the management of COPD

Clinical data on adverse events • Risk of pneumonia was taken from pooled analysis (ACLIFORM and AUGMENT)  No statistical significant difference was observed between the treatment arms  The same weighted average was applied in both arms (0.0097=21/2158 cases per year/0.0008 per month). OWSA: 30% variability; PSA: Beta distribution • Risk of an exacerbation (Karabis et al. 2014 Oostenbrink et al. 2005) Mean (SD) Mild Moderate Severe Very severe Prob. of having an exacerbation 19% (1.5%) 19% (1.5%) 24% (1.8%) 30% (2.3%) Proportion of exacerbations treated in hospital 68.40% (5.2%) 68.40% (5.2%) 62.50%(4.8%) 66.70% (5.1%) OWSA: 15% variability; PSA: Beta distribution • Risk of dying (Boutou A. K. et.al. 2013)  Kaplan – Meier survival curves of four population groups categorized by GOLD stages  A linear extrapolation was used to obtain the probability of dying per month Mild Moderate Severe Very severe Probability of death per cycle per health state 0.00508 0.00596 0.00665 0.00812 Assessing the cost-effectiveness of using aclidinium 400µg / formoterol 12µg compared to aclidinium 400µg 8 in the management of COPD

Cost & utility data • Drug acquisition costs ( British National Formulary , 2014) Treatment Price/pack # Dose DDD Cost/DDD Cost/month Aclidinium £28.60 60 2 £0.95 £29.02 Aclidinium/formoterol £32.50 60 2 £1.08 £32.97 • Management cost and resource use per health state (Personal Social Services Research Unit, 2013; National Schedule of Reference Cost, 2012/13 ; British National Formulary . 2014; Oostenbrink et al. 2005) • Event costs (Samyshkin et al. 2014) Cost of managing COPD Utility  exacerbation treated in community Health state (Mean=SD) Mean (CI)  exacerbation treated in hospital Mild £7.53 0.787 (0.771;0.802)  pneumonia treated in hospital Moderate £22.41 Severe £55.16 0.750 (0.731;0.768) Very Severe 0.647 (0.598;0.695) £164.75 • Year 2014 • Utilities per health state (Rutten-van Mölken et al. 2006) Cost Utility reduction COPD event (Mean=SD) Mean (SD) Exacerbation treated in • Utility reductions for exacerbation and £1,423 0.85 (0.077) hospital care pneumonia (Oostenbrink et al. 2005) Exacerbation treated in £68 community care 0.5 (0.051) Treating pneumonia £2,267 Cost: OWSA-30% variability, PSA-Gama distribution and Briggs assumption; Utility: OWSA-CI, PSA-Beta distributions; Utility reduction OWSA-20% variability, PSA-Normal distribution Assessing the cost-effectiveness of using aclidinium 400µg / formoterol 12µg compared to aclidinium 400µg 9 in the management of COPD