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): September 22, 2010
THERAVANCE, INC.
(Exact Name of Registrant as Specified in its Charter)
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Delaware (State or Other Jurisdiction of |
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000-30319 (Commission File Number) |
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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):
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.
Today at the European Respiratory Society Annual Congress in Barcelona, Spain, GlaxoSmithKline plc presented two oral presentations: Phase 2 study of RELOVAIR™, a once-daily combination medicine of fluticasone furoate (FF), the inhaled corticosteroid (ICS), and vilanterol trifenatate (VI), the long-acting beta2 agonist (LABA) in patients with chronic obstructive pulmonary disease (COPD) and Phase 2b study of VI in patients with asthma. RELOVAIR™ is being developed for the treatment of patients with COPD or asthma under the LABA collaboration between GSK and Theravance, Inc. The two presentations are filed as Exhibit 99.1 and Exhibit 99.2 to this report and are incorporated herein by reference.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
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Exhibit |
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Description |
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Exhibit 99.1 |
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Safety and efficacy of fluticasone furoate/vilanterol trifenatate (FF/VI) in COPD patients |
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Exhibit 99.2 |
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24h duration of the novel long-acting b2 agonist vilanterol trifenatate in uncontrolled asthma |
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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THERAVANCE, INC. |
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Date: September 22, 2010 |
By: |
/s/ Michael W. Aguiar |
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Michael W. Aguiar |
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Chief Financial Officer |
EXHIBIT INDEX
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Exhibit |
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Description |
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Exhibit 99.1 |
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Safety and efficacy of fluticasone furoate/vilanterol trifenatate (FF/VI) in COPD patients |
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Exhibit 99.2 |
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24h duration of the novel long-acting b2 agonist vilanterol trifenatate in uncontrolled asthma |
Exhibit 99.1
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Safety and efficacy of fluticasone furoate/vilanterol trifenatate (FF/VI) in COPD patients J Lötvall1, P Bakke2, L Bjermer3, S Steinshamn4, C Crim5, L Sanford6, C Scott-Wilson5, B Haumann6 1Krefting Research Centre, University of Gothenburg, Gothenberg, Sweden 2Department of Thoracic Medicine, University of Bergen and Haukeland University Hospital, Bergen, Norway 3Department of Respiratory Medicine and Allergology, Institute for Clinical Science, Lund, Sweden 4Lung Department, St. Olavs University Hospital of Trondheim, Trondheim, Norway 5Respiratory Medicine Development Centre, GlaxoSmithKline, RTP, USA 6Respiratory Medicine Development Centre, GlaxoSmithKline, London, UK |
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CONFLICT OF INTEREST DISCLOSURE Jan Lötvall has the following, real or perceived conflicts of interest: Served as a consultant to, and received lecture fees from, or been sponsored to attend congresses by: AstraZeneca GlaxoSmithKline Merck Sharpe and Dohme Novartis Oriel Therapeutics UCB Pharma |
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ACKNOWLEDGEMENTS Funded by GlaxoSmithKline Editorial support by Gardiner-Caldwell Communications, funded by GlaxoSmithKline Investigators and staff at the four study centres |
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Fluticasone furoate (FF) Novel ICS - 24h activity Vilanterol trifenatate (VI) Novel LABA - 24h activity 25mcg optimal dose FF and VI (FF/VI) Developed as once-daily combination treatment for COPD and asthma Current ICS/LABA therapies are indicated twice-daily ICS/LABA therapies can be further improved Background FF and VI combination |
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COPD Safety Tolerability Efficacy Co-primary endpoints Change in heart rate (HR 0–4h) Adverse events Secondary endpoints Change in trough FEV1 on Days 2, 15 and 29 Serial FEV1 on Days 1 and 28 Time to 100mL increase in FEV1 on Day 1 Objectives and endpoints, FF/VI once daily |
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Screening 7 days FF/VI (400/25mcg) OD (morning) Placebo OD (morning) Follow-up 4 weeks 1 week Treatment Study design 40-80 years of age at Visit 1 Clinical history of COPD (ATS/ERS) Current or prior smoking history of 10 pack years Post-salbutamol FEV1/FVC ratio of 0.70 Post-salbutamol FEV1 between 40 and 80% predicted at Visit 1 |
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60 randomised patients 40 patients – FF/VI (400/25mcg) OD 20 patients – placebo 5 patients withdrew 3 adverse events (2 placebo) 1 protocol deviation (placebo) 1 lost to follow-up (placebo) Intention To Treat (ITT): |
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Similar between groups: Mean age 63.6 years 33% female Smoking history 37% current smokers; 63% former smokers Mean pack years = 33.8 Screening lung function Mean FEV1 %: 59% Mean FEV1/FVC: 54% Mean reversibility FEV1: 15.6% (231mL) Demographics and lung function |
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Time course of FEV1: Day 1 0 30 60 120 240 0.35 0.30 0.25 0.20 0.15 0.10 0.05 0.0 –0.05 –0.10 Minutes after inhalation FF/VI (400/25mcg) OD Placebo OD FEV1 mean change from baseline (L) 65% > 100ml at 5 minutes |
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Time course of FEV1: Day 28 Minutes after inhalation 0.35 0.30 0.25 0.20 0.15 0.10 0.05 0.0 –0.05 –0.10 0 30 60 120 240 FF/VI (400/25mcg) OD Placebo OD FEV1 mean change from baseline (L) |
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trough FEV1 0.35 0.30 0.25 0.20 0.15 0.10 0.05 0.0 2 15 29 Day FF/VI (400/25mcg) OD Placebo OD FEV1 mean change from baseline (L) |
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Adjusted mean change from baseline in weighted mean FEV1 1 28 0.35 0.30 0.25 0.20 0.15 0.10 0.05 0.0 –0.05 Day FF/VI (400/25mcg) OD Placebo OD FEV1 mean change from baseline (L) |
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n (%) Placebo (N=20) FF/VI (400/25mcg) OD (N=40) Any event 10 (50) 27 (68) Nasopharyngitis 3 (15) 7 (18) Headache 1 (5) 6 (15) Oral candidiasis 0 (0) 3 (8) Dizziness 1 (5) 2 (5) Chest Pain 1 (5) 1 (3) Dysphonia 0 (0) 2 (5) Common adverse events (>1 patient) |
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Adjusted mean change from baseline in weighted mean heart rate 6 4 2 0 –2 –4 –6 –8 –10 –12 Mean change from baseline (bpm) 1 14 28 FF/VI (400/25mcg) OD Placebo OD Day |
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Adjusted mean change from baseline in maximum heart rate 6 4 2 0 –2 –4 –6 –8 –10 –12 Mean change from baseline (bpm) 1 14 28 FF/VI (400/25mcg) OD Placebo OD Day |
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Adjusted mean change from baseline in weighted mean diastolic BP 2 0 –2 –4 –6 –8 –10 –12 –14 Mean change from baseline (mmHg) 1 14 28 FF/VI (400/25mcg) OD Placebo OD Day |
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Adjusted mean change from baseline in weighted mean QTcF 20 15 10 5 0 –5 –10 –15 Mean change from baseline (msec) 1 14 28 FF/VI (400/25mcg) OD Placebo OD Day |
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Adjusted mean change from baseline in maximum QTcF 20 15 10 5 0 –5 –10 –15 Mean change from baseline (msec) 1 14 28 FF/VI (400/25mcg) OD Placebo OD Day |
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FF/VI demonstrated a clear improvement in 24h trough and serial FEV1 FF/VI was well tolerated over the 28-day treatment period FF/VI showed no adverse impact on HR or other vital signs FF/VI demonstrated no clinically relevant impact on QTc Summary |
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FF/VI is well tolerated and induces improvements in lung function in patients with COPD FF/VI may function as a once-daily combination therapy in COPD Conclusions |
Exhibit 99.2
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24h duration of the novel long-acting 2 agonist vilanterol trifenatate in uncontrolled asthma Lötvall J1, Bateman ED2, Bleecker ER3, Busse W4, Woodcock A5, Follows R6, Lim J6, Stone S6, Jacques L6, Haumann B6 1Krefting Research Centre, University of Gothenburg, Gothenburg, Sweden 2Department of Medicine, University of Cape Town, Cape Town, South Africa 3Translational Sciences, Wake Forest University Health Sciences, Winston-Salem, NC, USA 4Department of Medicine, University of Wisconsin, Madison, WI, USA 5School of Translational Medicine, University of Manchester, Manchester, UK 6Respiratory Medicine Development Centre, GlaxoSmithKline, London, UK |
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Conflict of interest disclosure Jan Lötvall has the following, real or perceived conflicts of interest: Served as a consultant to, and received lecture fees from, or been sponsored to attend congresses by: AstraZeneca GlaxoSmithKline Merck Sharpe and Dohme Novartis Oriel Therapeutics UCB Pharma |
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Acknowledgements Funded by GlaxoSmithKline Editorial support by Gardiner-Caldwell Communications, funded by GlaxoSmithKline Study management: Suus Baggen (GlaxoSmithKline) Investigators and staff 88 centres |
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Background Adding a LABA to ICS improves asthma control Current ICS/LABA therapies are indicated twice-daily ICS/LABA therapies can be further improved Adherence may improve with once daily treatment Vilanterol trifenatate (VI) Novel, inhaled LABA Inherent 24h activity Clinical efficacy not previously presented In development as combination therapy Asthma COPD |
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Study objectives To evaluate VI in asthma Dose response Clinical efficacy Safety Five doses of VI / Placebo Dosing in evening Persistent asthma Regular treatment ICS |
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Study design Multicentre, randomised, double-blind, placebo-controlled, parallel-group, dose-ranging study Endpoints primary: trough FEV1 Day 28 secondary: Mean 24h FEV1 Symptom-free days Safety and tolerability |
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VI 12.5mcg VI 6.25mcg VI 3mcg VI 25mcg Follow-up PLACEBO VI 50mcg –2 weeks 1 week 28 days of treatment R Run-in 12 years of age at Visit 1 History of persistent asthma FEV1 reversibility 12% and 200 mL Maintenance ICS Pre-bronchodilator FEV1 between 40 and 90% predicted at Visit 1 |
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Patient demographics Across treatment groups Mean age 40-44 years; 50–60% female Screening lung function Mean pre-bronchodilator FEV1: 2.1–2.3L (65–68%) Mean reversibility: 24–27% |
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Time course of FEV1: Day 1 (difference from placebo) Change in FEV1 (mL) Time (hours) 300 250 200 150 100 50 0 VI 25mcg VI 6.25mcg VI 12.5mcg VI 50mcg VI 3mcg 0 2 4 6 8 10 12 14 16 18 20 22 24 |
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Proportion of patients with FEV1 200mL & 12%: Day 1 Time (hours) % 70 60 50 40 30 20 0 2 4 6 8 10 12 14 16 18 20 22 24 VI 25mcg VI 6.25mcg VI 12.5mcg VI 50mcg placebo VI 3mcg |
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Proportion of patients with FEV1 200mL & 12%: Day 28 VI 25mcg VI 6.25mcg VI 12.5mcg VI 50mcg 70 60 50 40 30 20 0 2 4 6 8 10 12 14 16 18 20 22 24 % Time (hours) placebo VI 3mcg |
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Change in baseline trough FEV1 day 28 300 3mcg 6.25mcg 12.5mcg 25mcg 50mcg 200 100 0 -100 VI dose Difference from placebo and 95% CI (mL) |
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Percentage of symptom-free 24h periods 40 3mcg 6.25mcg 12.5mcg 25mcg 50mcg 35 30 25 20 15 10 5 0 -5 VI dose Difference from placebo and 95% CI (mL) |
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LABA-class associated AEs Headache (all groups) 7–12% VI, 8% placebo Tremor: 2 patients (6.25mcg) Glucose tolerance (1 patient 12.5mcg) Blood glucose levels: 1 patient (50mcg VI; unrelated to treatment) No AEs of low potassium reported No dose-dependent increases in AEs No serious AEs reported in any group No effect observed on QTcf |
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Conclusions In patients receiving maintenance ICS, VI: FEV1 duration of 24h at dose 12.5mcg Beneficial therapeutic ratio at 12.5mcg - 50mcg Optimal dose: 25mcg Is well tolerated Developed as a once-daily ICS/LABA combination therapy for asthma/COPD |
