EX-99.1 2 a14-12968_2ex99d1.htm EX-99.1

Exhibit 99.1

 

Efficacy and safety of once-daily fluticasone furoate/vilanterol (FF/VI)

and FF over 12 weeks in patients with persistent asthma

 

Poster #407

 

Bernstein DI(1), Bateman ED(2), Woodcock A(3), Toler WT(4), Forth R(5), Jacques L(6), Nunn C(6), O’Byrne PM(7)

 

(1)College of Medicine, University of Cincinnati, Cincinnati, OH, USA; (2)Department of Medicine, University of Cape Town, Cape Town, South Africa; (3)Institute of Inflammation and Repair, University of Manchester, Manchester, UK; (4)Respiratory Medicines Development Center, GlaxoSmithKline, RTP, NC, USA; (5)Quantitative Sciences Division, GlaxoSmithKline, RTP, NC, USA; (6)Respiratory Medicines Development Centre, GlaxoSmithKline, London, UK; (7)Michael G DeGroote School of Medicine, Hamilton, ON, Canada

 

INTRODUCTION

 

·             Treatment guidelines for persistent asthma in patients not controlled with inhaled corticosteroid (ICS) therapy alone recommend an ICS with a long-acting beta2 agonist (LABA),(1) leading to improved lung function and asthma symptom control compared with ICS monotherapy.(2)

 

·             FF is an ICS in development as a once-daily (OD) monotherapy and available as a combination therapy with the LABA VI (FF/VI) for the treatment of COPD in the USA and for COPD and asthma in the EU and a number of other countries.(3),(4)

 

·             FF/VI 200/25mcg OD significantly improves lung function and symptomatic endpoints compared with FF alone,(5) while numeric benefits have been reported for FF/VI 100/25mcg compared with FF 100mcg.(6)

 

OBJECTIVES

 

·             To compare the efficacy and safety of OD FF/VI 100/25mcg with FF 100mcg in patients with moderate-to-severe, persistent bronchial asthma over 12 weeks.

 

·             To assess the relative efficacy of FF/VI 100/25mcg with FF/VI 200/25mcg in these patients (descriptive comparison only).

 

METHODS

 

·             Phase III, multicenter, randomized, double-blind, parallel-group study.

 

·             Patient inclusion criteria: >12 years of age; FEV1 40–80% predicted; demonstrated >12% and >200mL reversibility to albuterol; receiving ICS for >12 weeks pre-study and stable with a mid-to-high dose ICS or mid-dose ICS/LABA for 4 weeks pre-study.

 

·             Following a 4-week run-in without LABA, patients symptomatic or using rescue on >4 of the last 7 days of run-in were randomized 1:1:1 (stratified by baseline forced expiratory volume in one second [FEV1], <65% versus >65%) to FF 100mcg, FF/VI 100/25mcg or FF/VI 200/25mcg administered in the evening via the ELLIPTA™ dry powder inhaler OD for 12 weeks.

 

·             Primary and secondary endpoints were analyzed using ANCOVA (covariates of baseline, region, sex, age and treatment) with a step-down statistical hierarchy for FF 100mcg versus FF/VI 100/25mcg.

 

RESULTS

 

·             Of 2019 patients screened, 1039 were randomized and received at least one dose of study medication (intent-to-treat [ITT] population; Table 1), with 90% of patients completing the study.

 


 

Table 1. Baseline demographics (ITT population)

 

 

 

FF 100mcg

 

FF/VI 100/25mcg

 

FF/VI 200/25mcg

 

 

 

N=347

 

N=346

 

N=346

 

Age, years

 

44.7 (15.89)

 

45.9 (16.14)

 

46.6 (14.72)

 

Female sex, n (%)

 

199 (57)

 

205 (59)

 

224 (65)

 

Pre-bronchodilator FEV1, L

 

1.965 (0.5980)(a)

 

1.985 (0.5563)(a)

 

1.954 (0.5819)(b)

 

Percent predicted FEV1

 

61.13 (10.348)(a)

 

62.64 (10.148)(a)

 

62.12 (10.050)(b)

 

Percent reversibility

 

30.79 (19.153)(c)

 

29.10 (16.537)(a)

 

29.33 (15.701)(b)

 

Rescue-free 24-h periods, %

 

4.4 (12.07)

 

4.4 (12.58)

 

5.8 (16.00)

 

Symptom-free 24-h periods, %

 

4.8 (14.63)

 

3.8 (14.38)

 

4.6 (15.44)

 

 

Values are mean (SD) unless otherwise stated. (a)n=342; (b)n=344; (c)n=346

 

Efficacy endpoints

 

·             There were statistically significant improvements with FF/VI 100/25mcg versus FF 100mcg for the primary endpoint of weighted mean 0–24h FEV1 (Figs. 1–2) and the secondary and ‘other’ endpoints, except for AQLQ score (Fig. 1).

 

·             There were numerical improvements for all efficacy endpoints with FF/VI 200/25mcg versus FF/VI 100/25mcg (Fig. 3).

 

Figure 1. Adjusted treatment differences and ratios for efficacy
endpoints: FF/VI 100/25mcg versus FF 100mcg (ITT population)

 

 

ACT = Asthma Control Test™; AQLQ = Asthma Quality of Life Questionnaire; CI = confidence interval; PEF = peak expiratory flow; wm = weighted mean

 


 

Figure 2. Adjusted mean change from baseline of individual
serial FEV1 assessments at Week 12 (ITT population)

 

 

LS = least squares

 

Figure 3. Adjusted treatment differences and ratios for efficacy
endpoints: FF/VI 200/25mcg versus 100/25mcg (ITT population)

 

 

Safety (Table 2)

 

·             Incidence of AEs and serious AEs (SAEs) were similar across treatments; there were no post-treatment SAEs and no fatal AEs.

 


 

Table 2. Summary of AE incidence and most commonly
reported on-treatment AEs (ITT population)

 

 

 

FF

 

FF/VI

 

FF/VI

 

 

 

100mcg

 

100/25mcg

 

200/25mcg

 

n (%)

 

N=347

 

N=346

 

N=346

 

AEs

 

 

 

 

 

 

 

Any on-treatment

 

127 (37)

 

127 (37)

 

123 (36)

 

Drug-related(a),(b)

 

11 (3)

 

7 (2)

 

8 (2)

 

Leading to permanent discontinuation or withdrawal(b)

 

4 (1)

 

3 (1)

 

3 (<1)

 

Serious AEs

 

 

 

 

 

 

 

Any on-treatment

 

3 (<1)(c)

 

4 (1)(d)

 

1 (<1)(e)

 

Drug-related(a),(b)

 

1 (<1)

 

0

 

0

 

Most common (>3%) on-treatment AEs in any treatment group

 

 

 

 

 

 

 

Headache

 

32 (9)

 

29 (8)

 

29 (8)

 

Nasopharyngitis

 

26 (7)

 

22 (6)

 

25 (7)

 

Upper respiratory tract infection

 

12 (3)

 

8 (2)

 

7 (2)

 

Influenza

 

4 (1)

 

10 (3)

 

9 (3)

 

 

(a)investigator’s judgement of causality; (b)includes on-treatment and post-treatment AEs;

(c)2 pneumonia, 1 borderline mucinous ovarian tumour; (d)biliary colic, acute pancreatitis, thermal burn, occipital neuralgia; (e)abortion threatened

 

CONCLUSIONS

 

·             There were statistically significant improvements in lung function and symptoms with FF/VI 100/25mcg versus FF 100mcg after 12 weeks of treatment in patients with moderate-to-severe persistent bronchial asthma.

 

·             Numerical improvements were seen for FF/VI 200/25mcg versus FF/VI 100/25mcg across all endpoints with patients on FF/VI 200/25mcg being 55% more likely to be well controlled than those on FF/VI 100/25mcg.

 

·             No new safety concerns were identified for any of the study treatments.

 

REFERENCES

 

(1)         Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention 2012. http://www.ginasthma.com/Guidelines/guidelines-resources.html (accessed 3/20/2014).

(2)         Ducharme FM, et al. Cochrane Database Syst Rev 2010;10:CD005533.

(3)         Breo Ellipta Medication Guide. Food and Drug Administration. www.fda.gov/downloads/drugs/drugsafety/ucm352347.pdf (accessed 4/08/2014).

(4)         EPAR Summary For The Public. European Medicines Agency. www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/ 002673/WC500157636.pdf (accessed 4/08/2014).

(5)         O’Byrne PM, et al. Eur Respir J 2014;43:773–82.

(6)         Bleecker ER, et al. J Allergy Clin Immunol Pract 2014; ePub ahead of print (25 April 2014).

 

ACKNOWLEDGEMENTS

 

·             The presenting author, WT Toler, is an employee of and holds stock in GlaxoSmithKline.

·             This study was funded by GlaxoSmithKline (HZA116863, NCT01686633).

·             Editorial support (in the form of writing assistance, assembling tables and figures, collating author comments, grammatical editing and referencing) was provided by David Cutler, PhD at Gardiner-Caldwell Communications (Macclesfield, UK) and was funded by GlaxoSmithKline.

 

ELLIPTA™ is a trade mark of GlaxoSmithKline

 

 

 

Presented at the American Thoracic Society Annual Congress, San Diego, CA, USA, 16–21 May 2014