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):  May 20, 2013

THERAVANCE, INC.

(Exact Name of Registrant as Specified in its Charter)

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):

o            Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

o            Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

o            Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

o            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 May 20, 2013 at the American Thoracic Society International Conference in Philadelphia, Pennsylvania, GlaxoSmithKline plc (GSK) presented posters containing information from Phase 3b studies of the combination treatment fluticasone furoate/vilanterol (FF/VI) and a Phase 3 study of the combination treatment umeclidinium bromide (UMEC)/VI.  FF/VI, known in the United States as BREO™ ELLIPTA™ (100/25mcg), recently gained U.S. Food and Drug Administration approval as an inhaled long-term, once-daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.  It is also indicated to reduce exacerbations of COPD in patients with a history of exacerbations.  It is not indicated for the relief of acute bronchospasm or the treatment of asthma.  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.  It is not currently approved or licensed in the European Union or anywhere outside of the U.S.  UMEC, a long-acting muscarinic antagonist, combined with VI, a LABA, is a once-daily investigational medicine for the maintenance treatment of patients with COPD.  FF/VI and UMEC/VI are in development under the LABA collaboration agreement between GSK and Theravance, Inc.  The posters are filed as Exhibits 99.1 to 99.2 to this report and are incorporated herein by reference.

Item 9.01 Financial Statements and Exhibits.

(d)         Exhibits

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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.

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EXHIBIT INDEX

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Exhibit 99.1

POSTER NO. 806

Once-daily (OD) fluticasone furoate/vilanterol 100/25mcg (FF/VI) compared with twice-daily (BD) fluticasone propionate/salmeterol 250/50mcg (FSC) in patients with COPD

Dransfield M(1), Crim C(2), Feldman G(3), Korenblat P(4), LaForce C(5), Locantore N(2), Pistolesi M(6), Watkins M(2), Martinez F(7)

(1)University of Alabama, Birmingham, AL, USA; (2)GlaxoSmithKline, Research Triangle Park, NC, USA; (3)S. Carolina Pharmaceutical Research, SC, USA; (4)The Clinical Research Center, St Louis, MO, USA; (5)North Carolina Clinical Research, Raleigh, NC, USA; (6)University of Florence, Florence, Italy; (7)University of Michigan, Ann Arbor, MI, USA

INTRODUCTION

·        Currently available ICS/LABA combinations for moderate/severe COPD require twice-daily dosing.

·        FF and VI are, respectively, a novel ICS and LABA in development as a once-daily combination therapy (FF/VI) for COPD and asthma.

OBJECTIVES

·        To compare the efficacy and safety profiles of once-daily FF/VI 100/25mcg with twice-daily FSC (250/50mcg) in patients with moderate/severe COPD.

METHODS

·        Two randomized, double-blind, double-dummy, multi-center parallel-group studies (HZC109 [Study 1] and HZC352 [Study 2]), of 12 weeks duration, were identical in design, conduct and analysis.

·        Patients (>40 years of age, >10 pack-years smoking history, post-bronchodilator FEV1 <70%, FEV1/FVC ratio <0.70 at screening, no requirement of prior exacerbations) completed a 2-week placebo run-in and were randomized 1:1 to once-daily (morning) FF/VI 100/25 via the ELLIPTA™ two-strip dry powder inhaler, or twice-daily FSC 250/50 via DISKUS™.

·        Primary endpoint was change from baseline in weighted mean (wm) 0–24h FEV1 on Day 84. Secondary endpoint was time to onset on Day 1. Safety was assessed throughout the study.

·        Outcomes of the individual studies and pooled data are presented. A step-down statistical hierarchy was applied to analysis of the individual studies but not the pooled data. In Study 1 and Study 2, a statistically significant (p<0.05) treatment difference on the primary endpoint was required for statistical inference to be drawn on subsequent endpoints.

RESULTS

·        1030 patients (Study 1: 519; Study 2: 511) were randomized and received at least one dose of study medication (intent-to-treat [ITT] population). 950 completed the studies. On-treatment withdrawal rates were 8% in both treatment arms.

·        Patient demographics were well matched (Table 1).

Table 1. Patient demographics and screening characteristics

(pooled data, ITT population)

Values are mean (SD) unless otherwise stated

Efficacy: primary endpoint

·        Change from baseline in 0–24h wmFEV1 on Day 84 was significantly (p<0.001) greater with FF/VI than with FSC in Study 1 and in the pooled analysis, but not in Study 2 (Table 2).

·        An overall pattern of greater lung function over 24h on Day 84 was observed with FF/VI compared with FSC (Figure 1).

Table 2. Change from baseline 0–24h wmFEV1 (mL) after 12 weeks

(Study 1, Study 2 & pooled, ITT population)

Values are least squares mean (SD) unless otherwise stated

Figure 1. LS mean FEV1 change from baseline over 24h, Day 84

(pooled data, ITT population)

CI=confidence interval; LS=least squares

Efficacy: secondary endpoint

·        Median time to >100mL increase from baseline FEV1 was significantly faster with FF/VI (15–16min) than FSC (30min) in Study 1 (p=0.012) and in the pooled analysis (p=0.026) (Figure 2), but significance could not be inferred for Study 2 (FF/VI: 16min, FSC: 30min).

Figure 2. Cumulative % of patients achieving >100mL increase

from baseline FEV1, Day 1 (pooled data, ITT population)

Table 3. Summary of on-treatment AEs by treatment group

(pooled data, ITT population)

AEs occurring in >3% of patients in either treatment group shown

AE=adverse event, SAE=serious adverse event

Safety

·        AE frequency was similar between treatment groups (Table 3).

·        No abnormalities of clinical concern were observed in either study for laboratory values, including urinary cortisol, or ECG readings.

·        A statistically significant treatment difference (FF/VI - FSC) in 0–4h weighted mean pulse rate (95% CI) of –1.9bpm (–3.3, –0.5) was observed at Week 12 in Study 1; this difference was not considered to be clinically significant. No difference in weighted mean pulse rate was observed between FF/VI and FSC in Study 2.

CONCLUSIONS

·        Pooled analysis of these two replicate studies found once-daily FF/VI 100/25 to produce a greater improvement in 24h lung function than twice-daily FSC 250/50 after 12 weeks of treatment.

·        FF/VI confers a more rapid improvement in lung function than FSC in the first hour of dosing on Day 1.

·        No baseline factors that may explain the differential outcomes of Study 1 and Study 2 were apparent.

·        No substantial safety concerns were identified in relation to FF/VI. Both treatments were well tolerated overall with similar safety profiles.

ACKNOWLEDGMENTS

·        The presenting author, Mark Dransfield, declares the following real or perceived conflicts of interest during the last 3 years in relation to this presentation: has served as a consultant for Boehringer Ingelheim (BI), GlaxoSmithKline (GSK) and Ikaria. He has received grant funding from the NHLBI for COPD-related research and contracted research funding from Aeris, AstraZeneca, BI, Boston Scientific, Centocor, Forrest, GSK, Ikaria, MedImmune, Otsuka and Pfizer.

·        This research was funded by GlaxoSmithKline. GSK study codes (clinicaltrials.gov): HZC113109 (NCT01323634); HZC112352 (NCT01323621).

·        Editorial support (in the form of writing assistance, assembling tables and figures, collating author comments, grammatical editing and referencing) was provided by Ian Grieve, 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, Philadelphia, PA, USA, 17–22 May 2013

Exhibit 99.2

Poster No. 39941

Efficacy and safety of once-daily umeclidinium/vilanterol 125/25mcg in patients with COPD

Celli, B(1), Crater, G(2), Kilbride, S(3), Mehta, R(2), Tabberer, M(3), Kalberg, C.J.(2), Church, A(2)

(1)Brigham and Women’s Hospital, Boston, MA, USA (2)GlaxoSmithKline, Research Triangle Park, NC, USA (3)GlaxoSmithKline, Stockley Park, Uxbridge, UK

INTRODUCTION

·        Current guidelines recommend treatment with one or more long-acting bronchodilators for patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD).(1),(2)

·        Umeclidinium (UMEC)/vilanterol (VI) is a novel long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) combination bronchodilator in development for the maintenance treatment of COPD.

OBJECTIVES

·        To evaluate the efficacy and safety of once-daily UMEC/VI 125/25 mcg compared with its components (UMEC and VI) and placebo in patients with COPD.

METHODS

Study design and treatment

·        Multicenter, randomized, double-blind, placebo-controlled, parallel-group study (ClinicalTrials.gov: NCT01313637; protocol number: DB2113361).

·        Key eligibility criteria:  >40 years of age; clinically established history of COPD; current or former cigarette smokers with >10-pack-year smoking history; post-albuterol forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) <0.7 and predicted FEV1 <70%; and a mMRC dyspnea scale score >2.

·        Following a 7 to 14 day run-in, patients were randomized 3:3:3:2 to 24 weeks treatment with UMEC/VI 125/25mcg, UMEC 125mcg, VI 25mcg or placebo once-daily via the ELLIPTATM dry powder inhaler. Concurrent use of inhaled corticosteroids (ICS) and rescue albuterol was allowed.

·        All patients were required to provide written informed consent prior to study participation. The study was conducted in accordance with the declaration of Helsinki, Good Clinical Practice guidelines, and IRB approval was obtained.

Endpoints

·        Primary efficacy: trough FEV1 on Day 169 defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on treatment Day 168.

·        Additional efficacy included: 0–6h post-dose weighted mean (WM) FEV1; transition dyspnea index (TDI) focal score; St George’s Respiratory Questionnaire (SGRQ) score; rescue albuterol use; and time to first COPD exacerbation.

·        Safety: adverse events (AEs); vital signs; 12-lead ECG and 24-h Holter electrocardiography (ECG); and clinical chemistry and hematology.

·        Plasma pharmacokinetics (PK) were analyzed using population PK methodology.

RESULTS

Patient demographics and baseline characteristics

·        A total of 2114 patients were enrolled; 1489 were included in the intention-to-treat (ITT) population (i.e., randomized and received at least one dose of study medication).

·        Patient demographics and baseline characteristics were similar across treatment groups (Table 1). ICS use was similar across active treatment groups (44–47%) and placebo (50%).

TABLE 1. PATIENT DEMOGRAPHICS AND BASELINE CHARACTERISTICS

Values are reported as mean (standard deviation) unless otherwise stated.

(a) Defined as current medical history of angina, myocardial infarction, stroke, diabetes, hypertension, or hyperlipidemia.

(b) Reversible was an increase in FEV1 of >12% and >200 mL following administration of 4 puffs of albuterol.

Efficacy: Trough FEV1

·        Treatment with UMEC/VI 125/25 resulted in statistically significant improvements in trough FEV1 at Day 169 vs. VI, UMEC 125 and placebo (p<0.001, Table 2). Comparisons at all other visits were statistically significant (p<0.001, Figure 1). All comparisons of UMEC 125 and VI vs. placebo were statistically significant (p<0.001).

FIGURE 1. TROUGH FEV1 (ITT POPULATION)

Efficacy: additional endpoints

·        Greater improvements in 0–6h post-dose WM FEV1 were shown for UMEC/VI 125/25 vs. VI, UMEC 125 and placebo (p<0.001 for all comparisons at all visits, Figure 2 and Table 2). Both UMEC 125 and VI consistently improved 0–6h post-dose WM FEV1 vs. placebo (p<0.001, Table 2).

·        Greater improvements in TDI focal score, SGRQ score, and rescue albuterol use were shown with UMEC/VI 125/25 compared with placebo (Table 2).

·        The incidence of COPD exacerbations was lower with UMEC/VI 125/25 (6%), UMEC 125 (8%) and VI (8%) compared with placebo (14%). Analysis of time to first exacerbation showed that patients on UMEC/VI 125/25 had a lower risk of exacerbation vs. placebo (hazard ratio: 0.4; 95% CI: 0.2, 0.6 [p<0.001]; corresponding to a risk reduction of 60%).

TABLE 2: EFFICACY ENDPOINT COMPARISONS

(ITT POPULATION)

(a)         Values are differences in least squares mean (95% CI); OR, odds ratio (based on proportion of responders according to outcome measure. *p<0.001 vs placebo, † p<0.005 vs placebo, ‡ p<0.05 vs monotherapy. To account for multiplicity across treatment comparisons and endpoints, a step-down closed testing procedure was used.

Safety and pharmacokinetics

·        Headache and nasopharyngitis were the most common AEs reported (Table 3).. The incidence of dry mouth was low (UMEC/VI 125/25 [2%] and <1% for UMEC 125, VI, and placebo).

·        The incidence of SAEs was similar across treatment groups (5–6%). The most common SAE was COPD (<1–3%).

·        Six deaths were reported (2 events of metastatic cancer in the UMEC 125 and VI groups; arteriosclerosis and pneumonia in placebo group; metastatic pancreatic carcinoma in UMEC 125 group; acute myocardial infarction in VI group).

·        No clinically meaningful treatment-related changes in vital signs, ECG, or clinical laboratory parameters were observed for active treatments compared with placebo.

·        There were no differences in the systemic exposure of UMEC 125 or VI when administered in combination or as monotherapy. In addition, patient demographics did not influence PK parameters of either compound.

FIGURE 2: 0–6h POST-DOSE WM FEV1 (ITT POPULATION)

TABLE 3: OVERVIEW OF ADVERSE EVENTS

(ITT POPULATION)

CONCLUSIONS

·        Once-daily dosing with UMEC/VI 125/25 improved lung function compared with the UMEC and VI monotherapies, and placebo in patients with COPD. Other assessments supported the efficacy of UMEC/VI 125/25.

·        Safety and tolerability profiles of UMEC/VI 125/25 were similar to the monotherapies and placebo.

·        This study supports the use of UMEC/VI 125/25 as a long-term maintenance treatment in COPD.

REFERENCES

(1)         GOLD 2013. Available at: http://www.Goldcopd.org/ Last accessed March 2013.

(2)         Celli BR, Macnee W. Eur Respir J 2004; 23:932-946.

ACKNOWLEDGEMENTS

·        B.C. has participated in advisory boards for GlaxoSmithKline, Boehringer Ingelheim, Almirall, AstraZeneca, Aeris, DeepBreeze, Takeda, Novartis. GC, SK, RM, MT, CK and AC are employees of GlaxoSmithKline and hold stocks/shares in GlaxoSmithKline.

·        This study was sponsored by GlaxoSmithKline (ClinicalTrials.gov: NCT01313637; protocol number: DB2113361).

·        Editorial support was provided by David Griffiths, PhD (in the form of writing assistance, assembling tables and figures, collating author comments, grammatical editing and referencing), from Fishawack Scientific Communications Ltd, funded by GlaxoSmithKline.

Presented at the Annual Congress of the American Thoracic Society (ATS), Philadelphia, PA, USA, May 17–22, 2013