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): October 23, 2012
THERAVANCE, INC.
(Exact Name of Registrant as Specified in its Charter)
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Delaware |
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000-30319 |
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94-3265960 |
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(State or Other Jurisdiction of |
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(Commission File Number) |
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(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 7.01 Regulation FD Disclosure.
The information contained in this Item 7.01 and in the accompanying exhibit shall not be deemed filed for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or incorporated by reference in any filing under the Exchange Act or the Securities Act of 1933, as amended, except as shall be expressly set forth by specific reference in such filing.
On October 23, 2012 at the United European Gastroenterology Week, Amsterdam, Netherlands, Theravance, Inc. presented data from the Phase 2b Study 0084 with TD-1211 in patients with opioid-induced constipation (OIC). These Phase 2b data were also presented on October 23, 2012, at the American College of Gastroenterology’s 77th Annual Scientific Meeting, Las Vegas, Nevada. TD-1211 is an investigational once-daily, orally administered, peripherally selective, multivalent inhibitor of the mu opioid receptor designed with a goal of alleviating gastrointestinal side effects of opioid therapy without affecting analgesia. A copy of the slide presentation is furnished as Exhibit 99.1 to this report and is 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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Slide Presentation Titled “TD-1211 Demonstrates Improvement in Bowel Movement Frequency and Bristol Stool Scores in a Phase 2b Study of Patients with Opioid-Induced Constipation (OIC)” |
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: October 23, 2012 |
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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Slide Presentation Titled “TD-1211 Demonstrates Improvement in Bowel Movement Frequency and Bristol Stool Scores in a Phase 2b Study of Patients with Opioid-Induced Constipation (OIC)” |
Exhibit 99.1
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TD-1211 Demonstrates Improvement in Bowel Movement Frequency and Bristol Stool Scores in a Phase 2b Study of Patients with Opioid-Induced Constipation (OIC) Daniel Canafax, PharmD VP, Clinical Research Theravance, Inc. Ross Vickery, PhD,1 Yu-Ping Li, PhD,1 Ullrich Schwertschlag, MD, PhD,1 Neil Singla, MD,2 Lynn Webster, MD,3 Daniel Canafax, PharmD1 1 Theravance, Inc., So. San Francisco, CA; 2 Lotus Clinical Research, Pasadena, CA; 3 Lifetree Clinical Research, Salt Lake City, UT |
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Disclosures . Dr. Canafax is an employee of Theravance, Inc. . Theravance, Inc., is investigating TD-1211 as a potential new treatment option for OIC |
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TD-1211 for Opioid-Induced Constipation . Theravance-discovered, multivalent, µ-opioid receptor neutral antagonist . Peripherally selective . Designed to normalize bowel movement frequency and quality . Once daily oral dosing |
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Phase 2b Study 0084 Design . Randomized, double-blind, placebo-controlled study . TD-1211 doses: 5, 10, 15 mg, or placebo, once daily . Study duration: 5-weeks treatment . Initiation with 5 mg TD-1211 or placebo once daily for 4 days . Non-cancer pain patients with chronic OIC . <5 SBMs during a 2-week baseline period, and . >1 additional symptom of constipation for >25% of bowel movements . Chronic opioid use . Total daily dose of >30 mg morphine equivalent units . Stable opioid regimen >14 days . Protocol-permitted rescue laxative SBM = spontaneous bowel movement |
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Patient Demographics . Baseline characteristics similar across all treatment groups MEU = morphine equivalent unit Patients randomized 217 Mean age, yrs (range) 49 (21–65) % female 59% Mean duration of OIC, years ± SD 6.0 ± 5.6 Mean baseline SBMs/week 1.1–1.2 Mean opioid dose, MEU (range) 145 (30–1740) Most common reason for chronic opioid use Back pain, 43% |
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Primary Endpoint - Change From Baseline in Average Weekly CSBMs Over Weeks 2 to 5 of Treatment LS means difference = least squares mean difference from placebo; Efficacy Analysis (EA) population LS mean difference = 0.97 p=0.0413 LS mean difference = 1.61 p=0.0010 LS mean difference = 1.79 p=0.0003 0 1 2 3 4 5 6 7 Placebo TD-1211 5 mg TD-1211 10 mg TD-1211 15 mg 0.2 (n=52) 0.1 (n=53) 0.3 (n=49) 0.2 (n=47) 1.0 (n=50) 1.6 (n=46) 3.0 (n=47) 2.7 (n=45) Mean Weekly Average CSBMs + SD Bsl Wk2-5 Complete Spontaneous Bowel Movements (CSBMs) Bsl Wk2-5 Bsl Wk2-5 Bsl Wk2-5 |
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Change From Baseline in Weekly CSBMs During Week 5 of Treatment LS means difference = least squares mean difference from placebo; EA population . Durable response observed through Week 5 0 1 2 3 4 5 6 7 0.2 (n=52) 0.1 (n=53) 0.3 (n=49) 0.2 (n=47) 0.9 (n=50) 1.5 (n=47) 2.5 (n=47) 2.9 (n=46) Mean Number of CSBMs+ SD Complete Spontaneous Bowel Movements (CSBMs) p=0.0637 LS mean difference = 1.36 p=0.0095 LS mean difference = 2.04 p=0.0001 LS mean difference = 0.95 Placebo TD-1211 5 mg TD-1211 10 mg TD-1211 15 mg Bsl Wk2-5 Bsl Wk2-5 Bsl Wk2-5 Bsl Wk2-5 |
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Change From Baseline in Average Weekly SBMs Over Weeks 2 to 5 of Treatment LS means difference = least squares mean difference from placebo; EA population LS mean difference = 0.88 p=0.0739 LS mean difference = 1.46 p=0.0038 LS mean difference = 1.83 p=0.0003 Spontaneous Bowel Movements (SBMs) 0 1 2 3 4 5 6 7 8 Placebo TD-1211 5 mg TD-1211 10 mg TD-1211 15 mg 1.2 (n=52) 1.2 (n=53) 1.1 (n=49) 1.2 (n=47) 3.1 (n=50) 3.9 (n=46) 4.5 (n=47) 4.9 (n=45) Mean Weekly Average SBMs + SD Bsl Wk2-5 Bsl Wk2-5 Bsl Wk2-5 Bsl Wk2-5 |
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Pre-Specified Responder Analysis 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Placebo TD-1211 5 mg TD-1211 10 mg TD-1211 15 mg 39% (n=52) 59% p=0.0401 (n=53) 61% p=0.0222 (n=49) 70% p=0.0016 (n=47) Responders (%) EA population Responder definition: >3 SBMs per week and an increase of at least 1 SBM per week from baseline for >3 weeks over Weeks 2 to 5 |
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Patient’s Global Impression of Change in Constipation 0% 20% 40% 60% 80% 100% Placebo (47) TD-1211 5 mg (40) TD-1211 10 mg (38) TD-1211 15 mg (41) 9% 23% 29% 46% 13% 33% 24% 20% 32% 30% 21% 22% 47% 15% 26% 12% % Patients Reporting PGIC Score Treatment Group (n) PGIC Score (7-Point Scale) <4: No change or worse 5: A little better 6: Better 7: Much better p=0.0017 p=0.0033 p=0.0001 End of Treatment response to: “Since the end of the 2-week qualification period and before the first dose of study medication, how would you describe the change in your constipation?” |
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Time to First Bowel Movement Placebo n=52 TD-1211 Combined n=149 Number of patients with at least one SBM within: 4 hours 5 (10) 56 (38) 8 hours 9 (17) 77 (52) 16 hours 17 (33) 87 (58) 24 hours 30 (58) 99 (66) 48 hours 39 (75) 124 (83) Patients, n (%) SBMs = spontaneous bowel movements. EA population |
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Bristol Stool Scale Scores for SBMs at End of Treatment (Week 5) 0% 20% 40% 60% 80% 100% Placebo (45) TD-1211 5mg (44) TD-1211 10mg (41) TD-1211 15mg (40) 47% 30% 20% 15% 51% 57% 56% 75% 2% 14% 24% 10% Patients (%) with Average Bristol Stool Score at Wk 5 Treatment Group (n) Loose Stool (>5) Normal (>2 to <5) Hard, Dry (<2) . Patients with average BSS scores at baseline among treatment groups: 54-67% hard, dry and 29-43% normal BSS = Bristol Stool Scale; SBMs = spontaneous bowel movements |
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Overall TEAEs Similar Between TD-1211 and Placebo, with GI TEAEs Predominant Safety Population Placebo n=54 TD-1211 Dose Group All TD-1211 n=161 5 mg n=56 10 mg n=53 15 mg n=52 Any TEAE 24 (44) 22 (39) 29 (55) 22 (42) 73 (45) GI disorders (occurring in 42 patients) 11 (20) 13 (23) 15 (28) 14 (27) 42 (26) Abdominal pain 6 (11) 7 (13) 6 (11) 8 (15) 21 (13) Abdominal pain upper 1 (2) 2 (4) 3 (6) 2 (4) 7 (4) Diarrhea 0 4 (7) 6 (11) 4 (8) 14 (9) Flatulence 3 (6) 1 (2) 2 (4) 1 (2) 4 (3) Nausea 2 (4) 4 (7) 8 (15) 3 (6) 15 (9) Vomiting 1 (2) 4 (7) 1 (2) 0 5 (3) Patients, n (%) . A majority of treatment-related GI adverse events were associated with initiation of treatment, resolved within a few days, and were mild or moderate TEAEs = treatment-emergent adverse event; GI = gastrointestinal |
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Average Daily Pain Scores (0-10 scale) Per Week EA population. Weeks 6 +7 = follow-up period |
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Summary of Study 0084 . TD-1211 was generally well tolerated . No clinically significant laboratory, ECG, or vital sign abnormalities . No treatment-related SAEs . No evidence of CNS penetration, interference with analgesia, or central withdrawal . Majority of patients reported their constipation was better or much better on treatment . Clinically meaningful response to treatment |
