Download THERAVANCE INC (Form: 8-K, Received: 11/12

UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, DC 20549
FORM 8-K
Current Report Pursuant
to Section 13 or 15(d) of the
Securities Exchange Act of 1934
Date of Report (Date of earliest event Reported): November 12, 2013
THERAVANCE, INC.
(Exact Name of Registrant as Specified in its Charter)
Delaware
(State or Other Jurisdiction of
Incorporation)
000-30319
(Commission File Number)
94-3265960
(I.R.S. Employer Identification Number)
901 Gateway Boulevard
South San Francisco , California 94080
(650) 808-6000
(Addresses, including zip code, and telephone numbers, including area code, of principal executive offices)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of
the following provisions (see General Instruction A.2. below):

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Item 8.01 Other Events.
On November 12, 2013 at the 18 th Congress of the Asian Pacific Society of Respirology, Yokohama, Japan, GlaxoSmithKline plc (“GSK”)
presented a poster on a Phase 3 study of the once-daily treatment combination of fluticasone furoate “FF”, an inhaled corticosteroid, and
vilanterol “VI”, a long-acting beta 2 agonist, (FF/VI 200/25 mcg) in asthma patients of Asian ancestry. In September 2013, the Japanese
Ministry of Health, Labour and Welfare (MHLW) approved FF/VI for the treatment of bronchial asthma (in cases where concurrent use of
inhaled corticosteroid and long-acting inhaled beta 2 agonist is required). FF/VI is not indicated for the treatment of chronic obstructive
pulmonary disease (COPD) in Japan. The MHLW has approved two doses of FF/VI - 100/25 mcg and 200/25 mcg. Both strengths will be
administered once-daily using the ELLIPTA™, a new dry powder inhaler. RELVAR ® ELLIPTA™ is the trade name in Japan. FF/VI
remains in development elsewhere in the world for the maintenance treatment of asthma and COPD, with pending marketing authorization
applications in a number of countries. FF/VI for the treatment of COPD is approved in the United States and Canada. FF/VI is not indicated
for the relief of acute bronchospasm or the treatment of asthma in the United States or Canada. FF/VI is not approved or licensed anywhere
outside of the United States, Japan and Canada. FF/VI is in development under the LABA collaboration agreement between Glaxo Group
Limited and Theravance, Inc. The poster is filed as Exhibit 99.1 to this report and is incorporated herein by reference.
Item 9.01 Financial Statements and Exhibits.
(d)
Exhibits.
Exhibit
Exhibit 99.1
Description
Efficacy and safety of once-daily fluticasone furoate/vilanterol 200/25mcg compared with
twice-daily fluticasone propionate 500mcg in asthma patients of Asian ancestry
2
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf
by the undersigned hereunto duly authorized.
THERAVANCE, INC.
Date: November 12, 2013
By:
3
/s/ Michael W. Aguiar
Michael W. Aguiar
Chief Financial Officer
EXHIBIT INDEX
Exhibit No.
Description
99.1
Efficacy and safety of once-daily fluticasone furoate/vilanterol 200/25mcg compared with twice-daily fluticasone
propionate 500mcg in asthma patients of Asian ancestry
4
Exhibit 99.1
POSTER NO. PS108
Efficacy and safety of once-daily fluticasone furoate/vilanterol 200/25mcg compared with twice-daily fluticasone propionate 500mcg in
asthma patients of Asian ancestry
Jiangtao L(1), Crawford J(2), Jacques L(3), Stone S(3)
(1)Department of Respiratory Diseases, China-Japan Friendship Hospital, Beijing 100029, China
(2)Quantitative Sciences Division, GlaxoSmithKline, Uxbridge, UK
(3)Respiratory Medicines Development Centre, GlaxoSmithKline, Uxbridge, UK
INTRODUCTION

Fluticasone furoate (FF)/vilanterol (VI) is a novel once-daily ICS/long-acting beta 2 -agonist (LABA) combination therapy for the
treatment of asthma.

Fluticasone proprionate (FP) is an inhaled corticosteroid (ICS) taken twice daily via the DISKUS TM inhaler for the treatment of
asthma.

FF/VI delivered via the ELLIPTA TM dry powder inhaler, has demonstrated 24h effectiveness in asthma patients in global
studies(1),(2)


The 200/25mcg strength significantly improved lung function versus FP 500mcg twice daily over 24 weeks.(2)
Responses to pharmacotherapy can vary across ethnic groups,(3),(4) including in Asian patients.(4)
OBJECTIVES

To evaluate the efficacy and safety of once-daily FF/VI 200/25mcg administered in the evening, compared with twice-daily FP
500mcg administered in the morning and evening, in asthma patients of Asian ancestry.
METHODS

A randomised, double-blind, double-dummy, active-comparator, parallel-group, 12-week multicentre study.

Inclusion criteria: aged > 12 years; FEV 1 40–90% predicted; reversibility of > 12% and > 200mL within 10–40 minutes following
2–4 inhalations of salbutamol; treated with stable high-dose ICS or mid-dose ICS/LABA therapy for > 4 weeks prior to Screening.

Patients were randomised (1:1) to receive FF/VI 200/25mcg once daily via the ELLIPTA device (equivalent to a delivered dose of
FF/VI 184/22mcg) or FP 500mcg twice daily via the DISKUS inhaler for 12 weeks.

Primary endpoint: mean change from baseline in daily evening peak expiratory flow (PEF) averaged over the 12-week treatment
period.

Secondary endpoints (Weeks 1–12, unless stated)
 Change from baseline in % rescue-free 24h periods
 Mean change from baseline in morning PEF (averaged over Weeks 1–12)
 Change from baseline in % symptom-free 24h periods


Change from baseline in AQLQ+12 Total score (measured at Week 12).
A step-down statistical hierarchy was applied to account for multiplicity across endpoints. Testing of each endpoint was dependent on
the achievement of significance at the 5% level for the previous endpoint, in the following order

Evening PEF > % rescue-free 24h periods > morning PEF > % symptom-free 24h periods > AQLQ score.

Safety endpoints included incidence of adverse events (AEs), vital signs, electrocardiogram and laboratory evaluations.
RESULTS
Table 1. Demographic and baseline characteristics
(ITT population)
Age (years)
Male, n (%)
Duration of asthma
(years)
Lung function parameters
FEV 1 (L)
% predicted FEV 1
% reversibility FEV 1
at screening
FF/VI 200/25
OD
N=155
FP 500
BD
N=154
Total
N=309
46.9 (12.93)
59 (38)
12.39
(12.857)
48.8 (13.41)
68 (44)
13.44
(13.551)
47.9 (13.19)
127 (41)
12.91
(13.196)
1.78 (0.493)
67.51
(13.249)
27.31
(14.570)
1.77 (0.552)
67.55
(13.432)
26.98
(14.262)
1.77 (0.523)
67.53
(13.319)
27.14
(14.395)
Data are mean (SD) unless otherwise stated; OD=once daily; BD=twice daily
RESULTS
Efficacy

FF/VI and FP improved evening PEF compared with baseline
( Figure 1 )



Change from baseline with FF/VI was 39.1L/min (standard error=3.01) and with FP was 10.5L/min (3.03)
The effect was statistically significantly better (p<0.001) with FF/VI compared with FP (28.5L/min; 95% confidence interval [CI]:
20.1, 36.9).
Improvements in % rescue-free 24h periods were similar for FF/VI and FP

The equivalent number of rescue-free days per week was 2.3 with FF/VI and 2.2 with FP

The adjusted treatment difference (1.0%; 95% CI: —7.3, 9.2) was not statistically significant (p=0.821) ( Figure 2 ).

Due to the statistical hierarchy, significance for remaining endpoints could not be inferred.

There were numerical improvements in the remaining secondary endpoints for FF/VI compared with FP ( Figure 2 ).
RESULTS
Safety

Incidence of AEs, treatment-related AEs and serious AEs was low and similar for FF/VI and FP ( Table 2 ).

There were no fatal AEs.

The only treatment-related SAE was asthma (FP 500mcg).

Pneumonia was reported by two patients (both with FF/VI 200/25mcg); neither required hospitalisation.

There were no clinically significant changes in vital signs, electrocardiogram parameters or clinical laboratory evaluations.
Table 2. Summary of adverse events (ITT population)
All AEs
On-treatment
On-treatment, treatment-related
On-treatment leading to withdrawal
Post-treatment
SeriousAEs
On-treatment
On-treatment, treatment-related
Most frequent (a) on-treatment AEs
Upper respiratory tract infection
Nasopharyngitis
Rhinitis allergic
Oropharyngeal pain
FF/VI 200/25
OD
N=155
FP 500
BD
N=154
40 (26)
5 (3)
2 (1)
0
41 (27)
5 (3)
2 (1)
1 (<1)
1 (<1)
0
2 (1)
1 (<1)
13 (8)
6 (4)
5 (3)
4 (3)
18 (12)
6 (4)
2 (1)
1 (<1)
(a)Occurring in > 3% of patients in either treatment group
CONCLUSIONS

FF/VI 200/25mcg once daily demonstrated clinically and statistically significant improvements in evening PEF compared with FP
500mcg twice daily in Asian asthma patients uncontrolled on high-dose ICS or mid-dose ICS/LABA.

There were numerical improvements across the secondary endpoints with FF/VI 200/25mcg versus FP 500mcg.

The safety profile of FF/VI 200/25mcg was broadly similar to that of FP 500mcg.

The results are generally consistent with a previously published global study that compared FF/VI 200/25mcg with FP 500mcg.(2)
REFERENCES
(1)
(2)
(3)
(4)
Woodcock A, et al. Chest 2013;144:1222–9.
O’Byrne PM, et al. Eur Respir J 2013;Oct 17:ePub ahead of print.
Bjornsson TD,et al. J Clin Pharmacol 2003;43:943–67.
Huang SM, et al. Clin Pharmacol Ther 2008;84:287–94.
ACKNOWLEDGMENTS

The presenting author, Dr Jiangtao Lin has received speaker’s honoraria from AstraZeneca, GlaxoSmithKline and MSD, and has been
a member of global advisory boards for Boehringer Ingelheim.

The study was funded by GlaxoSmithKline (GSK study code HZA113714 (clinicaltrials.gov registration number: NCT01498653).

Editorial support (in the form of writing assistance, assembling tables and figures, collating author comments, grammatical editing and
referencing) was provided by Laura Maguire, MChem at Gardiner-Caldwell Communications (Macclesfield, UK) and was funded by
GlaxoSmithKline.
DISKUS™ and ELLIPTA™ are trade marks of the GlaxoSmithKline group of companies
Presented at the 18 th Congress of the Asian Pacific Society of Respirology, Yokohama, Japan, 11–14 November 2013