Bevespi Aerosphere. Product Analysis. Bevespi Aerosphere. Product Analysis. Contact Us

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1 Bevespi Aerosphere Product Analysis Bevespi Aerosphere Product Analysis Ref Code: DMKC Publication Date: 08/04/2016 Author: Christina Vasiliou Contact Us Datamonitor America 52 Vanderbilt Ave, 7th Floor, New York, NY USA t: e: Datamonitor Europe 119 Farringdon Road, London, EC1R 3ER, United Kingdom t: e: Datamonitor Asia Pacific Level 7 / 120 Sussex Street, Sydney, NSW 2000, Australia t: e: apinfo@datamonitor.com Datamonitor Japan Da Vinci Ginza East 7th Floor, Ginza, Chuo-ku, Tokyo , Japan t: e: jpinfo@datamonitor.com

2 Reference: DMKC First published: 08/04/2016 About Datamonitor Healthcare Bringing you a clearer, richer and more responsive view of the pharma & healthcare market. Complete market coverage Our independent research and analysis provides extensive coverage of major disease areas, companies and strategic issues, giving you the perspective to identify opportunities and threats arising from shifting market dynamics and the insights to respond with faster, more effective decision-making. Unique expert capabilities With teams located across developed and emerging pharma markets, we are uniquely placed to understand local healthcare trends and provide accurate and reliable recommendations. By working closely with our partners at MedTrack, Citeline, SCRIP Intelligence and Informa Healthcare, our experts are able to share data and resources to produce the most authoritative and robust market intelligence. With over 700 clients across the pharma and biotech industries, we are relied upon to provide strategic guidance, not only through published analysis, but also tailored support solutions. Cutting-edge delivery Available through single reports or via subscription to our state-of-the art online intelligence service that features intuitive design and interactive capabilities, our analysis offers the definitive platform to enhance your product management, market assessment and strategic planning. Contact Us For more information about our products or to arrange a demo of the our online service, please contact: getcloser@datamonitorhealthcare.com Disclaimer All Rights Reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the publisher, Datamonitor Healthcare. The facts of this report are believed to be correct at the time of publication but cannot be guaranteed. Please note that the findings, conclusions and recommendations that Datamonitor Healthcare delivers will be based on information gathered in good faith from both primary and secondary sources, whose accuracy we are not always in a position to guarantee. As such, Datamonitor Healthcare can accept no liability whatsoever for actions taken based on any information that may subsequently prove to be incorrect. For more information about our products or to arrange a demonstration of the our online service, please contact: getcloser@datamonitorhealthcare.com 2

3 TABLE OF CONTENTS 4 PRODUCT PROFILES 4 Bevespi Aerosphere : Chronic obstructive pulmonary disease LIST OF FIGURES 11 Figure 1: Bevespi Aerosphere for COPD SWOT analysis 12 Figure 2: Datamonitor Healthcare's drug assessment summary of Bevespi Aerosphere for COPD 12 Figure 3: Datamonitor Healthcare s drug assessment summary of Bevespi Aerosphere for COPD LIST OF TABLES 4 Table 1: Bevespi Aerosphere drug profile 7 Table 2: Bevespi Aerosphere pivotal trial data in COPD 10 Table 3: Bevespi Aerosphere late-phase trial data in COPD 3

4 PRODUCT PROFILES Bevespi Aerosphere : Chronic obstructive pulmonary disease PRODUCT PROFILE Analyst Outlook While Bevespi Aerosphere (formoterol/glycopyrrolate; AstraZeneca) demonstrated statistically significant improvements in trough forced expiratory volume in one second (FEV1) compared to its individual components and placebo in its Phase III PINNACLE program, pulmonologists are unconvinced about its role in symptom improvement. Datamonitor Healthcare expects Bevespi Aerosphere to have significantly lower uptake compared to the most promising long-acting beta 2 agonist/long-acting muscarinic antagonist (LABA/LAMA) combinations, Ultibro (indacaterol/glycopyrronium bromide; Novartis/Pfizer) and Stiolto Respimat (olodaterol/tiotropium; Boehringer Ingelheim), despite AstraZeneca s experience in the respiratory market and strong marketing capabilities. Drug Overview Bevespi Aerosphere is a twice-daily fixed-dose combination of the LABA formoterol and the LAMA glycopyrrolate, delivered via a pressurized metered dose inhaler. 4

5 Table 1: Bevespi Aerosphere drug profile Molecule formoterol/glycopyrrolate Mechanism of action LABA/LAMA Originator Pearl Therapeutics Marketing company AstraZeneca Approved indication Long-term, maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema Formulation Pressurized metered dose inhaler Pricing strategy In line with the annual treatment cost of twice-daily Duaklir Genuair Dosing frequency Twice daily First approval date for COPD April 2016 (US) 2015 company-reported sales n/a Alternative names PT003 COPD = chronic obstructive pulmonary disease; LABA = long-acting beta 2 agonist; LAMA = long-acting muscarinic antagonist Source: Biomedtracker; Pharmaprojects DEVELOPMENT OVERVIEW In June 2013, AstraZeneca announced its acquisition of Pearl Therapeutics, giving the company access to Bevespi Aerosphere as well as other inhaler and formulation technology that provides a platform for future combination therapies. As part of the agreement, AstraZeneca had to make an initial payment of $560m to Pearl Therapeutics upon completion of the acquisition, while up to $450m was agreed to be paid if certain development and regulatory milestones are met. AstraZeneca will also pay up to $140m if pre-agreed cumulative sales thresholds are exceeded (AstraZeneca, 2013). In March 2015, AstraZeneca announced topline results from its two pivotal 24-week Phase III studies, PINNACLE 1 and PINNACLE 2, which assessed Bevespi Aerosphere s efficacy and safety in subjects with moderate to very severe chronic obstructive pulmonary disease (COPD). In both studies, Bevespi Aerosphere met the primary endpoint of achieving statistically significant improvements in trough 5

6 FEV1 compared to its individual components, glycopyrrolate (PT001) and formoterol fumarate (PT005), as well as placebo. Bevespi Aerosphere s individual components also demonstrated significant improvements in trough FEV1 compared to placebo. Based on these results, AstraZeneca submitted a New Drug Application for Bevespi Aerosphere for the treatment of COPD. The FDA accepted AstraZeneca s NDA in Q3 2015, and approved the drug for use in COPD in April 2016 (AstraZeneca, 2015a; AstraZeneca, 2015b; AstraZeneca, 2016). AstraZeneca plans to file for approval in Europe and Japan in H and 2017, respectively (Biomedtracker, 2016). Pivotal trial data Bevespi Aerosphere s pivotal Phase III studies are summarized in the table below. 6

7 Table 2: Bevespi Aerosphere pivotal trial data in COPD Trial Sample size Target patients Study design Treatment arms Results PINNACLE 1 2,103 Patients with 24-week, Arm 1: Adjusted mean peak change from baseline in FEV1 within two hours post-dose: glycopyrrolate/formoterol demonstrated moderate to very randomized, glycopyrrolate/form a nominally significant improvement versus placebo (mean difference of 288mL; p<0.0001), PT005 (81mL; p<0.0001), (NCT ) severe COPD double-blind, oterol (14.4/9.6μg) PT001 (123mL; p<0.0001), and open-label tiotropium (97mL; p<0.0001) over 24 weeks chronic-dosing, (Phase III) placebo-controlled, parallel-group, Symptom control as measured by change from baseline in average daily rescue Ventolin (salbutamol) use over 24 weeks: symptom control improvement was nominally significant for glycopyrrolate/formoterol compared with placebo (-1.08 multicenter study Arm 2: glycopyrrolate (14.4μg) puffs/day; p<0.0001) and compared with open-label tiotropium (-0.34 puffs/day; p=0.0126), with a difference of puffs/day versus PT001 (p=0.0619) and puffs/day versus PT005 (p=0.9683) over 24 weeks Arm 3: formoterol (9.6μg) Arm 4: open-label tiotropium DPI (18.0μg) taken as one capsule daily (active comparator) Arm 5: placebo 7

8 Table 2: Bevespi Aerosphere pivotal trial data in COPD Trial Sample size Target patients Study design Treatment arms Results PINNACLE 2 1,618 Patients with 24-week, Arm 1: Adjusted mean peak change from baseline in FEV1 within two hours post-dose: glycopyrrolate/formoterol demonstrated moderate to very randomized, glycopyrrolate/form a statistically significant improvement compared with placebo (278mL; p<0.0001), PT005 (76mL; p<0.0001), and PT001 (NCT ) severe COPD double-blind, oterol (14.4/9.6μg) (129mL; p<0.0001) over 24 weeks parallel-group, (Phase III) multicenter, Symptom control as measured by change from baseline in average daily rescue Ventolin (salbutamol) use over 24 weeks: chronic-dosing, symptom control was statistically significantly improved for glycopyrrolate/formoterol compared with placebo (-1.04 placebo-controlled Arm 2: puffs/day; p<0.0001), and PT001 (-0.57 puffs/day; p<0.0001), with a nominally significant difference of puffs/day study glycopyrrolate versus PT005 (p=0.0274) over 24 weeks. (14.4μg) Arm 3: formoterol (9.6μg) Arm 4: placebo BID = twice daily; COPD = chronic obstructive pulmonary disease; DPI = dry powder inhaler; FEV1 = forced expiratory volume in one second 8

9 Table 2: Bevespi Aerosphere pivotal trial data in COPD Source: Biomedtracker; Trialtrove; ClinicalTrials.gov 9

10 Other late-phase trials Other late-phase trial data for Bevespi Aerosphere in COPD are summarized in the table below. Table 3: Bevespi Aerosphere late-phase trial data in COPD Trial Sample size Target Study design Treatment Results patients arms PINNACLE Patients with 28-week, Arm 1: For changes from baseline in trough FEV1 and peak moderate to very multicenter, glycopyrrolate/fo FEV1 within two hours post-dose across 52 weeks of (NCT ) severe COPD randomized, rmoterol treatment, glycopyrrolate/formoterol demonstrated double-blind, (14.4/9.6μg) significant improvement versus formoterol (65 and (Phase III) parallel-group, 88ml, respectively), glycopyrrolate (57 and 129ml, active- respectively), and tiotropium (25ml and 93ml, controlled, safety respectively). extension study Arm 2: glycopyrrolate Glycopyrrolate/formoterol also demonstrated (14.4μg) significant improvements versus glycopyrrolate (p<0.0001) and open-label tiotropium (p=0.0002) for average daily use of rescue medication, and numerical improvement versus formoterol Arm 3: (p=0.0750). formoterol (9.6μg) Arm 4: openlabel tiotropium DPI (18.0μg) taken as one capsule daily (active comparator) BID = twice daily; COPD = chronic obstructive pulmonary disease; DPI = dry powder inhaler; FEV1 = forced expiratory volume in one second Source: Trialtrove; ClinicalTrials.gov; Hanania et al.,

11 SWOT ANALYSIS Figure 1: Bevespi Aerosphere for COPD SWOT analysis Source: Datamonitor Healthcare CLINICAL AND COMMERCIAL ATTRACTIVENESS The figures below show Datamonitor Healthcare s drug assessment summary of Bevespi Aerosphere in relation to the comparator drug Spiriva (tiotropium; Boehringer Ingelheim) and all of the other key 11

12 marketed and pipeline drugs profiled. Please see the Appendix for an explanation of Datamonitor Healthcare s drug assessment methodology. Figure 2: Datamonitor Healthcare's drug assessment summary of Bevespi Aerosphere for COPD Source: Datamonitor Healthcare 12

13 Figure 3: Datamonitor Healthcare s drug assessment summary of Bevespi Aerosphere for COPD Source: Datamonitor Healthcare Bevespi Aerosphere s clinical attractiveness suffers in comparison to that of its key competitors, despite its ambitious clinical trial program While Pearl Therapeutics now owned by AstraZeneca designed a strong clinical trial program for Bevespi Aerosphere, the drug s clinical performance to date has not been impressive. In its Phase III PINNACLE program, Bevespi Aerosphere was trialed against its individual components, glycopyrrolate (PT001) and formoterol fumarate (PT005), as well as the current gold-standard LAMA, Spiriva, and a placebo. Bevespi Aerosphere met the primary endpoint of achieving statistically significant improvements in trough FEV1 compared to its individual components and placebo in its PINNACLE 1 and PINNACLE 2 Phase III studies; however, it has not demonstrated any clear efficacy advantages over Spiriva to date (AstraZeneca, 2015b). Interviewed key opinion leaders are unconvinced about its role in symptom improvement, and note that its efficacy appears to be inferior to that of its key competitors, as well as AstraZeneca s other twice-daily LABA/LAMA combination, Duaklir Genuair (aclidinium/formoterol). PT003 is a twice-daily combination. It is based on a platform that seems to be universally usable for all kinds of drugs and that is the reason why AstraZeneca bought Pearl Therapeutics in 2013 [ ] The data that they presented so far regarding the LABA/LAMA on this Pearl [Therapeutics] platform are not perfect. I mean they are, from my perspective, not very convincing. I think if you do not have convincing data regarding symptom improvement you have a very hard time to get doctors to use your drug. So far they do not have good data regarding symptom improvement and if it stays that 13

14 way, I think they will have a hard time to gain a considerable market share, particularly as they already have another LABA/LAMA [Duaklir Genuair] in their own portfolio that has quite good data on symptom improvement. I guess in the US they might benefit from bringing this [PT003] to market before Duaklir. But things are getting very difficult for all these companies with LABA/LAMAs, especially when you have combinations out there like Ultibro and Stiolto that are already doing well. EU key opinion leader Datamonitor Healthcare believes Bevespi Aerosphere will struggle to capture significant share in the increasingly saturated COPD market, and forecasts the drug to be outperformed by the most promising LABA/LAMA combinations, Ultibro and Stiolto Respimat. Bibliography AstraZeneca (2013) AstraZeneca to acquire Pearl Therapeutics to strengthen respiratory portfolio. Available from: [Accessed 15 September 2016]. AstraZeneca (2015a) Year-To-Date and Q Results. Available from: releases/2015/q3/ %20results%20announcement%20q3%202015%20- %20%20Final%20copy.pdf [Accessed 15 September 2016]. AstraZeneca (2015b) AstraZeneca announces positive Phase III top-line results for PT003 from PINNACLE 1 and PINNACLE 2 studies in COPD. Available from: centre/press-releases/2015/astrazeneca-pt003-results-chronic-obstructive-pulmonary-disease html [Accessed 15 September 2016]. AstraZeneca (2016) Bevespi Aerosphere approved by the US FDA for patients with COPD. Available from: [Accessed 15 September 2016]. Hanania NA, Tashkin DP, Kerwin E, Donohue J, Denenberg M, O Donnel D, Quinn D, Siddiqui S, Orevillo C, Maes A, Reisner C (2016) Safety And Efficacy Of A Novel LAMA/LABA Co-Suspension Technology Glycopyrrolate/Formoterol Fixed-Dose Combination Delivered By MDI: Results Of A One-Year Extension Study In Patients With COPD (PINNACLE-3). Presented at the 2016 American Thoracic Society International Conference, San Francisco, California, May 2016; Abstract A