Press Release: Theravance Announces Positive Results From Phase 2 Clinical Trial
Theravance Announces Positive Results From Phase 2 Clinical Study in Chronic Constipation With Investigational Compound TD-5108 All Three Doses Studied Achieved Primary Endpoint SOUTH SAN FRANCISCO, CA - Theravance, Inc. today announced positive results from its 400-patient ACCORD Phase 2 clinical study in chronic constipation with TD-5108, an investigational compound for the treatment of chronic constipation and other disorders related to reduced gastrointestinal (GI) motility. In the study, all three doses of TD-5108 achieved statistical significance in the primary endpoint and key secondary endpoints. At the two lowest doses, TD-5108 was well tolerated with a low incidence of adverse events. All three doses of TD-5108 (15 mg, 30 mg, and 50 mg), given once daily, achieved the primary endpoint of an increased number of spontaneous bowel movements (SBM) per week over baseline compared with placebo. The average weekly increases over the four-week period in SBM from baseline for patients treated with TD-5108 were 3.6 for the 15 mg treatment group (p < 0.0001 versus placebo), 3.3 for the 30 mg group (p < 0.0001 versus placebo), and 3.5 for the 50 mg group (p < 0.0001 versus placebo). The average weekly increase in SBM from baseline for patients on placebo was 1.4. The increase from baseline in SBM for each TD-5108 treatment group was also statistically significant compared with placebo for each week. Over the four-week treatment period, 60% of the patients in the 15 mg treatment group, 42% of the 30 mg group, and 61% of the 50 mg group were classified as responders (patients who experienced at least three SBM for each of the four weeks), compared with 22% of patients on placebo; these results were statistically significant for all three groups. Compared with placebo, there was a statistically significant reduction in time to first SBM and a statistically significant increase in the percentage of patients who experienced an SBM within the first 24 hours for all groups treated with TD-5108. Overall, the most common adverse events included headache, diarrhea, nausea and vomiting. The incidence of these adverse events was greatest at the highest dose of TD-5108. There were no serious adverse events in the study. "There is a substantial unmet medical need for a medicine to treat patients with chronic constipation and other motility disorders of the GI tract," said Michael Kitt, MD, Senior Vice President of Development at Theravance. "We are very pleased with the quality and consistency of data in this large Phase 2 study which show increases in GI motility and adequate relief from chronic constipation in patients receiving TD-5108. I am especially excited that at the lower two doses TD-5108 showed a profound effect on GI motility with an excellent tolerability profile. We look forward to meeting with the FDA to discuss the development path for TD-5108." "Theravance has achieved another significant milestone with these Phase 2 results in our GI Motility Dysfunction program," said Rick Winningham, Chief Executive Officer. "We went from initiation of the first TD-5108 Phase 1 clinical study to completion of a 400-patient Phase 2 clinical study in only eighteen months. These positive proof-of-concept results validate the potential of our internally discovered and developed compounds to provide better treatment options that make a difference in people's lives." About ACCORD ACCORD (A randomized, plaCebo COntRolled, double-blind study of TD-5108) was a 28-day multi-center, randomized, double-blind, placebo-controlled study conducted in the United States comparing safety, efficacy, and tolerability of three doses of TD-5108 to placebo in patients with chronic constipation. A total of 400 patients were enrolled in this study on a 1:1:1:1 randomization to receive one of three doses of TD-5108 (15 mg, 30 mg, or 50 mg) or placebo, administered once daily. The mean baseline SBM was equal to or less than 1.3 per week for all groups. About TD-5108 TD-5108 was discovered by Theravance through the application of its multivalent drug design in a research program dedicated to finding new treatments for GI motility disorders. TD-5108 is a potent, highly selective agonist with high intrinsic activity at the 5-HT4 receptor. Relative to other 5-HT receptor types, TD-5108 is > 500-fold selective for binding to the human 5-HT4 receptor. Theravance anticipates that the high degree of selectivity of TD-5108 provides the potential for it to be a better and safer medicine for the treatment of patients with severe constipation and possibly constipation predominant irritable bowel syndrome. The goal of the GI Motility Dysfunction program is to develop an efficacious and well tolerated product with once-a-day oral dosing and few food restrictions. GSK Option Pursuant to the Company's 2004 Strategic Alliance with GlaxoSmithKline plc (GSK), GSK has an option to license TD-5108 for further development and commercialization under pre-agreed terms. For additional information regarding this agreement, please refer to SEC filings on the investor relations portion of Theravance's website at www.theravance.com. About Gastrointestinal Motility Dysfunction and Chronic Constipation Gastrointestinal motility dysfunction, a major contributing factor to many disorders of the GI tract, refers to the abnormal rate and coordination of food moving out of the stomach and through the rest of the digestive tract. Reduced GI motility can cause symptoms of bloating, nausea, pain and constipation and can adversely affect quality of life. Disorders of reduced motility include chronic constipation, constipation predominant irritable bowel syndrome, functional dyspepsia, and delayed gastric emptying. The prevalence of chronic constipation is estimated to be about 5% of the adult population in the United States. Conference Call and Webcast Information The Company has scheduled a conference call to discuss this announcement beginning at 8:00 a.m. Eastern Daylight Time on June 26, 2007. To participate in the live call by telephone, please dial 800-289-0572 from the U.S., or 913-981-5543 for international callers. Those interested in listening to the conference call live via the internet may do so by visiting the company's web site at www.theravance.com. To listen to the live call, please go to the web site 15 minutes prior to its start to register, download, and install any necessary audio software. A replay of the conference call will be available on the Company's web site for 30 days through July 26, 2007. An audio replay will be available through 11:59 p.m. Eastern Daylight Time on July 10, 2007 by dialing 888-203-1112 from the U.S., or 719-457-0820 for international callers, and entering confirmation code 6215644 . About Theravance Theravance is a biopharmaceutical company with a pipeline of internally discovered product candidates. Theravance is focused on the discovery, development and commercialization of small molecule medicines across a number of therapeutic areas including respiratory disease, bacterial infections and gastrointestinal motility dysfunction. Of the five programs in development, three are in late stage -- its telavancin program focusing on treating serious Gram-positive bacterial infections with Astellas Pharma Inc., its GI Motility Dysfunction program, and the Beyond Advair collaboration with GlaxoSmithKline. By leveraging its proprietary insight of multivalency to drug discovery focused on validated targets, Theravance is pursuing a next generation drug discovery strategy designed to discover superior medicines in large markets. For more information, please visit the company's web site at www.theravance.com. THERAVANCEÂ®, the Theravance logo, and MEDICINES THAT MAKE A DIFFERENCEÂ® are registered trademarks of Theravance, Inc. This press release contains and the conference call will contain certain "forward-looking" statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives and future events. Theravance intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Exchange Act and the Private Securities Litigation Reform Act of 1995. Examples of such statements include statements relating to the goals, timing and expected results of clinical and preclinical studies and regulatory review, statements regarding the potential benefits and mechanisms of action of drug candidates, the enabling capabilities of Theravance's approach to drug discovery and its proprietary insights, statements concerning expectations for product candidates through development and commercialization and projections of revenue and other financial items. These statements are based on the current estimates and assumptions of the management of Theravance as of the date of this press release and conference call are subject to risks, uncertainties, changes in circumstances, assumptions and other factors that may cause the actual results of Theravance to be materially different from those reflected in its forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include, among others, risks related to delays or difficulties in commencing or completing clinical and preclinical studies, the potential that results of clinical or preclinical studies indicate product candidates are unsafe, ineffective, inferior or not superior, delays or failure to achieve regulatory approvals, and risks of collaborating with third parties to develop and commercialize products. These and other risks are described in greater detail under the heading "Risk Factors" contained in Item 1A of Theravance's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on May 8, 2007 and the risks discussed in our other filings with the SEC. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Theravance assumes no obligation to update its forward-looking statements.