![]() Rifaximin Treatment in Non-Constipation Irritable Bowel Syndrome William P. Forbes, PharmD Executive Vice President, R&D and Chief Development Officer Salix Pharmaceuticals, Inc. Exhibit 99.1 |
![]() 2 Forward-Looking Statement Statements presented in this overview that are not historical facts are forward-looking statements that involve risks and uncertainties that could cause actual results to differ materially from projected results. Factors that could cause actual results to differ materially include the risks and uncertainties of clinical trials and regulatory review, anticipated losses and our need to return to profitability, intellectual property risks specifically patent protection, competition from generic products and otherwise, market acceptance of approved products, and the need to acquire new products. These and other relevant risks are detailed in the Company’s Securities and Exchange Commission filings. |
![]() 3 DDW2010 Investor Event Agenda Introduction and Background Bill Forbes, Pharm.D. Executive Vice President, Research and Development and Chief Development Officer Salix Pharmaceuticals TARGET 1 & 2 - Efficacy and Safety of Rifaximin 550 mg TID in the Treatment of Patients with Non–Constipation IBS Mark Pimentel, MD, FRCP (C) Associate Professor of Medicine, Geffen School of Medicine at UCLA Director, GI Motility Program, Cedars–Sinai Medical Center Question and Answer Philip Schoenfeld, MD, MSED, MSc Associate Professor, Department of Internal Medicine Division of Gastroenterology, The University of Michigan Closing Remarks Carolyn J. Logan President & CEO, Salix Pharmaceuticals |
![]() 4 Rifaximin US Regulatory Overview Major Salix US Development Programs Travelers’ Diarrhea NDA 21-361 Approved May, 2004 XIFAXAN ® 200 mg tablets (TID) Hepatic Encephalopathy NDA 22-554 Approved March, 2010 XIFAXAN ® 550 mg tablets (BID) Irritable Bowel Syndrome NDA: June, 2010 550 mg tablets (TID) |
![]() 5 FDA Approved Drugs for IBS IBS-C in women Safety: mild diarrhea, nausea, dyspnea Chloride-channel activator Amitiza Lubiprostone IBS-C in women Marketing suspended Safety: Severe cardiovascular side effects Contraindicated in severe renal impairment 5-HT 4 agonist Zelnorm Tegaserod Severe IBS-D in women not responding to conventional therapy Restricted access through Prescribing Program Safety: ischemic colitis & severe constipation Increased risk of AEs associated with increased exposure in hepatic impairment Drug-Drug Interactions: CYP1A2 or CYP3A4 inhibitors 5-HT 3 antagonist Lotronex Alosetron Efficacy / Safety Highlights Pharmacology Drug Camilleri and Andresen (2009) |
![]() 6 FDA / Salix IBS Regulatory Meetings • Primary Endpoint for TARGET 1 & 2 – Adequate relief of IBS Symptoms (SGA) during wks 3 – 6 • Secondary Endpoints for TARGET 1 & 2 and Long-term Safety: – Daily assessments of IBS Symptoms over 12 weeks – Use of HE data for long-term continuous dosing safety End of Ph 2 (Dec 2007) Pre-NDA (Dec 2009) • Primary Endpoint – EOP2 Agreements will be the basis of NDA review • Exploratory analyses using proposed FDA endpoint – Responder in both abdominal pain intensity and stool form • Safety database is adequate in size and exposure for NDA review – 1103 IBS subjects – 348 HE subjects (mean exposure = 364 days) • Co-primary Endpoints for Phase 2b – Adequate relief of IBS Symptoms (SGA) & IBS related bloating Pre-IND (Oct 2005) |
![]() 7 Comparative Rifaximin Exposure Rifaximin exposure in IBS – Similar to exposure in healthy subjects – More than 520-fold lower than rifampin exposure – More than 460-fold lower than norfloxacin exposure – More than 66-fold lower than neomycin exposure 0.1 1 10 100 1000 10000 0 1 2 3 4 5 6 7 8 Time (h) Rifampin 600 mg qd Norfloxacin 400 mg Neomycin 2 g Rifaximin 550 mg BID - HE Rifaximin 550 mg TID - healthy Rifaximin 550 mg TID - IBS |
![]() 8 Rifaximin Clinical Pharmacology Summary • Poorly absorbed (< 0.4%) – Low solubility and permeability (BCS 4) – P-glycoprotein efflux – > 99% excreted unchanged in feces – First-pass biliary clearance, minimal renal clearance – One known metabolite (~2.5% of parent) • No known safety signals – No inhibition of CYP450 – No clinically significant drug-drug interactions – Nonclinical studies indicate no QT risk • Clinical study will be conducted to confirm |
![]() 9 DDW2010 Investor Event Agenda Introduction and Background Bill Forbes, Pharm.D. Executive Vice President, Research and Development and Chief Development Officer Salix Pharmaceuticals TARGET 1 & 2 - Efficacy and Safety of Rifaximin 550 mg TID in the Treatment of Patients with Non–Constipation IBS Mark Pimentel, MD, FRCP (C) Associate Professor of Medicine, Geffen School of Medicine at UCLA Director, GI Motility Program, Cedars–Sinai Medical Center Question and Answer Philip Schoenfeld, MD, MSED, MSc Associate Professor, Department of Internal Medicine Division of Gastroenterology, The University of Michigan Closing Remarks Carolyn J. Logan President & CEO, Salix Pharmaceuticals |
![]() Rifaximin Treatment for 2 Weeks Provides Acute and Sustained Relief Over 12 Weeks of IBS Symptoms in Non-Constipated Irritable Bowel Syndrome: Results from 2 North American Phase 3 Trials, TARGET 1 & 2 M Pimentel, 1 A Lembo, 2 WD Chey, 3 S Zakko, 4 Y Ringel, 5 S Mareya, 6 J Yu, 6 A Shaw, 6 E Bortey, 6 WP Forbes 6 1 Cedars-Sinai Medical Center, Los Angeles, CA 2 Case Harvard Medical School, Boston, MA 3 University of Michigan Health System, Ann Arbor, MI 4 Connecticut Gastroenterology Institute, Bristol, CT 5 University of North Carolina at Chapel Hill, Chapel Hill, NC 6 Salix Pharmaceuticals, Inc., Morrisville, NC |
![]() 11 Disclosures • TARGET 1 and TARGET 2 were sponsored by Salix Pharmaceuticals, Inc. • Salix Pharmaceuticals is investigating rifaximin as a potential new treatment option for IBS • Rifaximin is not currently approved in the United States for the treatment of IBS • Dr. Pimentel was an investigator in the TARGET 2 study and has served as a consultant for Salix |
![]() 12 Irritable Bowel Syndrome (IBS) • IBS is a common chronic medical condition characterized by symptoms of abdominal pain, bloating, and altered bowel function in the absence of structural, inflammatory or biochemical abnormalities • For IBS patients – It impairs health-related quality of life, leading to increased health resource utilization and reduced work productivity • For Physicians – IBS is the most common condition diagnosed by gastroenterologists and the seventh most prevalent by all physicians – Therapeutic options are few and limited • Thus, there is an unmet need for effective, safe and well-tolerated therapies in IBS 1 Inadomi et. al., APT; 18 (7): 671-682, 2003. 1 |
![]() 13 Rationale for Antibiotics in IBS • GI microbiota play a role in IBS – Increased fermentation / gas 1 – SIBO 2 – Mucosal irritation / minimal Inflammation 3 – Altered stool bacterial composition 4 • Antibiotic therapy improves – IBS symptoms 5,6 1 King, et al. Lancet 1998;352:1187-9. 2 Posserud, et al. Gut 2007;56:802-8. Pimentel. Am J Gastro 2010;105:718-21. 3 King TS, et al. Lancet 1998;352:1187–9. Floch MH.Dig Liver Dis 2002;34(Suppl 2):S54–7. Barbara G, et al. Gut 2002;51(Suppl 1):i41–4. 4 Kassinen, et al. Gastroenterol 2007;133:24-33. 5 Pimentel, et al. Am J Gastro 2003;98:412-9. Sharara, et al. Am J Gastro 2006;101:326-33. Pimentel, et al. Ann Int Med 2006;145:557-63. Lembo, et al. Gastro 2008;134:A550. 6 Pimentel, et al. Am J Gastro 2003;98:412-9. Lauritano et al. APT 2005 1;22(1):31-35 |
![]() 14 Rationale for Rifaximin in IBS • Gut targeted • Minimally absorbed • Favorable safety / tolerability • Broad spectrum in vitro antibacterial activity • Low risk of antibiotic resistance / drug interactions • Effective in eradicating SIBO 1 • Demonstrated efficacy in IBS based on previous studies 1 Rifaximin is not indicated by the FDA for treatment of SIBO. |
![]() 15 TARGET 1 AND TARGET 2 • Two large scale, identically designed, randomized, double-blind, placebo-controlled registered trials • To study rifaximin 550mg or placebo TID for 14 days in non-constipation IBS • Conducted in parallel in the U. S. and Canada – TARGET 1: 95 centers (FPI, 06/04/08; LPO,08/17/09) – TARGET 2: 84 centers (FPI, 06/26/08; LPO,08/11/09) – Site participation unique to either TARGET 1 or 2 |
![]() 16 Key Entry Criteria Inclusion • 18 yrs of age with a colonoscopy within the last 2 years • IBS confirmed by Rome II criteria • Do not have adequate relief of IBS symptoms and IBS symptom of bloating • Average daily symptom scores during screening – Abdominal pain / discomfort (2 4.5; 7-point Likert scale) – Bloating (2 4.5; 7-point Likert scale) – Stool consistency ( 3.5; 5-point scale) Exclusion • History consistent with constipation predominant IBS • History of IBD, diabetes, unstable thyroid disease, previous abdominal surgery, HIV, renal or hepatic disease • Current use of alosetron, tegaserod, lubiprostone, antipsychotics, antispasmodics, antidepressants (except stable dose TCA or SSR), warfarin, antidiarrheals, probiotics, narcotics; antibiotics within 14 days, rifaximin within 60 days |
![]() 17 IBS-Related Bloating Subject’s Global Assessment (SGA) IBS Weekly Outcome Measures Yes / No In regards to your IBS symptoms, compared to the way you felt before you started study medication, have you, in the past 7 days, had adequate relief of your IBS symptoms? Yes / No In regards to your IBS symptom of bloating, compared to the way you felt before you started study medication, have you, in the past 7 days, had adequate relief of your symptom of bloating? |
![]() 18 4 = loose 5 = watery 1 = very hard 2 = hard 3 = formed On a scale of 1-5, what was the overall stool form of your bowel movements today? 0 = not at all 1 = hardly 2 = somewhat 3 = moderately 4 = a good deal 5 = a great deal 6 = a very great deal In regards to all your symptoms of IBS; on a scale of 0-6, how bothersome were your symptoms of IBS today? In regards to your specific IBS symptom of bloating; on a scale of 0-6, how bothersome was your IBS-related bloating today? In regards to your specific IBS symptom of abdominal pain and discomfort; on a scale of 0-6, how bothersome was your IBS-related abdominal pain and discomfort today? How many bowel movements did you have today? (whole number) Have you felt or experienced a sense of urgency today with any of your bowel movements? Yes / No Daily Outcome Measures |
![]() 19 SGA-IBS weekly 77 63 49 35 21 84 70 56 42 28 14 7 1 Day -13 IBS bloating weekly IBS symptoms daily QOL AEs & conmeds Vital signs Laboratory tests PEs Diary Eligibility Period No study medication Primary Evaluation Period Randomize 1:1 EOS Rfx 550 mg or placebo TID 10-Week Post-Treatment Phase 14-Day DB Treatment Screening Phase Study Design TARGET 1 and TARGET 2 |
![]() 20 Definition of Responder This was determined in 3 ways: 1. Based on Weekly Question – Subject’s Global Assessment of IBS – IBS-Bloating 2. Based on Daily Questions (SGA-IBS, IBS-Bloating, Abdominal Pain) – Weekly responder: rated symptoms (7-point scale) as either • 0 (not at all) or 1 (hardly) 50% of days in a given week; OR • 0 (not at all), 1 (hardly) or 2 (somewhat) 100% of days in a given week 3. Based on New FDA Draft Guidance Endpoint – Using daily question for weekly response: both abdominal pain and stool consistency • 30% decrease in mean abdominal pain score from baseline and a weekly mean stool consistency score of < 4 (5 point scale) in a given week Subjects were responders in a given month if they had a positive response during 2 out of 4 weeks |
![]() 21 Primary and Key Secondary Endpoints Primary Endpoint – Adequate relief for SGA-IBS during the primary evaluation period (weeks 3 - 6) Key Secondary Endpoint – Adequate relief of IBS bloating during the primary evaluation period (weeks 3 - 6) |
![]() 22 Patient Disposition Intent-to-Treat Population Intent-to-Treat: N = 1258 TARGET 2 n = 635 TARGET 1 n = 623 Discontinuation: n=26 (8.4%) •Adverse event: n=8 •Patient request: n=8 •Lost to FU: n=8 •Other: n=2 Placebo n = 314 Placebo n = 320 Discontinuation: n=22 (7.0%) •Adverse event: n=7 •Patient request: n=8 •Lost to FU: n=7 •Other: n=0 Discontinuation: n=15 (4.7%) •Adverse event: n=0 •Patient request: n=6 •Lost to FU: n=6 •Other: n=3 Discontinuation: n=19 (5.9%) •Adverse event: n=2 •Patient request: n=8 •Lost to FU: n=6 •Other: n=3 Rifaximin n = 309 Rifaximin n = 315 |
![]() 23 Demographics Intent-to-Treat Population 302 (94) 282 (90) 280 (89) 281 (91) White Race, n (%) 18 (6) 33 (10) 34 (11) 28 (9) Non-White 286 (91) 29 (9) 227 (72) 88 (28) 30 (10) 285 (90) 46 (14) Rifaximin (n=315) 292 (93) 22 (7) 222 (71) 92 (29) 38 (12) 276 (88) 46 (15) Placebo (n=314) 291 (91) 297 (96) Not Hispanic or Latino 12 (4) 235 (76) 74 (24) 34 (11) 275 (89) 46 (15) Rifaximin (n=309) Female Male Hispanic or Latino 65 years < 65 years 29 (9) Ethnicity, n (%) 225 (70) 95 (30) Sex, n (%) 37 (12) 283 (88) Age group, n (%) 46 (15) Mean age, y (SD) Placebo (n=320) Characteristic TARGET 1 TARGET 2 No difference was seen between groups or studies |
![]() 24 Baseline IBS Characteristics Intent-to-Treat Population Percentage of days with sense of urgency, mean (SD) Average daily bowel movements, mean (SD) Average daily scores, mean (SD) Duration of IBS symptoms, yr (SD) Characteristic 3.0 (1.5) 3.0 (1.6) 3.0 (1.4) 2.9 (1.3) 82.2 (22.5) 81.3 (22.8) 82.9 (22.3) 81.8 (22.3) 3.9 (0.3) 3.9 (0.3) 3.9 (0.3) 3.9 (0.3) Stool consistency 3.3 (0.7) 3.2 (0.7) 3.3 (0.7) 3.3 (0.8) Bloating 3.3 (0.7) 3.3 (0.7) 3.2 (0.7) 3.3 (0.7) Ab pain & discomfort 3.4 (0.7) 3.4 (0.7) 3.4 (0.7) 3.4 (0.7) IBS symptoms 10.8 (10.2) Rifaximin (n=315) 11.4 (11.9) Placebo (n=314) 11.9 (10.5) Rifaximin (n=309) 11.8 (10.4) Placebo (n=320) TARGET 1 TARGET 2 No difference was seen between groups or studies |
![]() 25 Primary Endpoint SGA IBS 41 41 41 32 32 31 0 10 20 30 40 50 TARGET 1 TARGET 2 Combined Data p = 0.0125 p = 0.0263 p = 0.0008 Responder: Patient responding ‘yes’ to adequate relief of SGA-IBS weekly question for 2 of the 4 weeks during weeks 3 - 6 Rifaximin Placebo |
![]() 26 40 41 40 29 32 30 0 10 20 30 40 50 TARGET 1 TARGET 2 Combined Data p = 0.0045 p = 0.0167 p = 0.0002 Key Secondary Endpoint IBS Bloating Responder: Patients who responded ‘yes’ to adequate relief of IBS-bloating weekly question for 2 of the 4 weeks during weeks 3 - 6 Rifaximin Placebo |
![]() ![]() ![]() 27 Consistency Across Endpoints Weeks 3 Through 6 IBS Bloating Weekly SGA-IBS Weekly Efficacy Outcome 0.0002 (1.23,1.96) 1.56 Combined 0.0167 (1.08,2.06) 1.49 TARGET 2 0.0045 (1.16,2.27) 1.62 TARGET 1 0.0008 (1.18,1.88) 1.49 Combined 0.0263 (1.05,2.01) 1.45 TARGET 2 0.0125 (1.10,2.12) 1.53 TARGET 1 p- value (95% CI) Odds Ratio Study IBS Bloating Weekly SGA-IBS Weekly Efficacy Outcome 0.0002 (1.23,1.96) 1.56 Combined 0.0167 (1.08,2.06) 1.49 TARGET 2 0.0045 (1.16,2.27) 1.62 TARGET 1 0.0008 (1.18,1.88) 1.49 Combined 0.0263 (1.05,2.01) 1.45 TARGET 2 0.0125 (1.10,2.12) 1.53 TARGET 1 p- value (95% CI) Odds Ratio Study Key Secondary Primary Odds Ratio and 95% CI 0.0 0.5 1.0 1.5 2.0 2.5 Favors Placebo Favors Rifaximin 0.0009 (1.17,1.84) 1.47 Combined 0.0077 (1.12,2.13) 1.55 TARGET 2 0.0401 (1.02,1.92) 1.40 TARGET 1 Ab Pain & Stool Daily (FDA) Stool Consist. Daily (FDA) Ab Pain Daily (FDA) <0.0001 (1.31,2.14) 1.67 Combined 0.0096 (1.12,2.21) 1.57 TARGET 2 0.0015 (1.25,2.59) 1.80 TARGET 1 0.0009 (1.17,1.83) 1.46 Combined 0.0194 (1.06,2.00) 1.46 TARGET 2 0.0157 (1.08,2.03) 1.48 TARGET 1 0.0009 (1.17,1.84) 1.47 Combined 0.0077 (1.12,2.13) 1.55 TARGET 2 0.0401 (1.02,1.92) 1.40 TARGET 1 Ab Pain & Stool Daily (FDA) Stool Consist. Daily (FDA) Ab Pain Daily (FDA) <0.0001 (1.31,2.14) 1.67 Combined 0.0096 (1.12,2.21) 1.57 TARGET 2 0.0015 (1.25,2.59) 1.80 TARGET 1 0.0009 (1.17,1.83) 1.46 Combined 0.0194 (1.06,2.00) 1.46 TARGET 2 0.0157 (1.08,2.03) 1.48 TARGET 1 FDA Proposed IBS Ab Pain Daily IBS Bloating Daily SGA-IBS Daily 0.0028 (1.13,1.78) 1.42 Combined 0.0232 (1.05,2.03) 1.46 TARGET 2 0.0255 (1.05,2.02) 1.45 TARGET 1 0.0004 (1.21,1.92) 1.52 Combined 0.0008 (1.26,2.44) 1.76 TARGET 2 0.0486 (1.01,1.97) 1.41 TARGET 1 <0.0001 (1.28,2.04) 1.61 Combined 0.0072 (1.13,2.24) 1.59 TARGET 2 0.0009 (1.26,2.47) 1.76 TARGET 1 IBS Ab Pain Daily IBS Bloating Daily SGA-IBS Daily 0.0028 (1.13,1.78) 1.42 Combined 0.0232 (1.05,2.03) 1.46 TARGET 2 0.0255 (1.05,2.02) 1.45 TARGET 1 0.0004 (1.21,1.92) 1.52 Combined 0.0008 (1.26,2.44) 1.76 TARGET 2 0.0486 (1.01,1.97) 1.41 TARGET 1 <0.0001 (1.28,2.04) 1.61 Combined 0.0072 (1.13,2.24) 1.59 TARGET 2 0.0009 (1.26,2.47) 1.76 TARGET 1 Other Secondary |
![]() 28 Daily SGA IBS Symptoms Change from Baseline at Wks 1 through 12 Change from Baseline in Average Daily Score of IBS Symptoms by Week - ITT Population (Combined Data) -1.10 -1.00 -0.90 -0.80 -0.70 -0.60 -0.50 -0.40 -0.30 -0.20 0 1 2 3 4 5 6 7 8 9 10 11 12 Week Rifaximin Placebo p-value < 0.050 Mean baseline = 3.39 2wk treatment 10wk post- treatment |
![]() 29 Rifaximin Placebo p-value < 0.050 2wk treatment 10wk post- treatment Change From Baseline in Daily IBS Symptom of Bloating by Week - ITT Population (Combined Data)) -1.10 -1.00 -0.90 -0.80 -0.70 -0.60 -0.50 -0.40 -0.30 -0.20 0 1 2 3 4 5 6 7 8 9 10 11 12 Week Mean baseline = 3.27 Daily IBS Bloating Change from Baseline at Wks 1 through 12 |
![]() 30 Rifaximin Placebo p-value < 0.050 2wk treatment 10wk post- treatment Change From Baseline in Daily IBS Symptom of Abdominal Pain & Discomfort by Week - ITT Population (Combined Data) -1.10 -1.00 -0.90 -0.80 -0.70 -0.60 -0.50 -0.40 -0.30 0 1 2 3 4 5 6 7 8 9 10 11 12 Week Daily IBS Abdominal Pain Change from Baseline at Wks 1 through 12 Mean baseline = 3.26 |
![]() 31 Consistency Across Endpoints Entire 3 Months Favors Placebo Favors Rifaximin Odds Ratio and 95% CI 0.0014 (1.14, 1.72) 1.40 Combined 0.0141 (1.08, 1.92) 1.44 TARGET 2 0.0396 (1.01, 1.83) 1.36 TARGET 1 Ab Pain & Stool Daily (FDA) IBS Bloating Weekly p-value (95% CI) Odds Ratio Study Efficacy Outcome <0.0001 (1.27, 1.97) 1.58 Combined 0.0114 (1.09, 2.00) 1.48 TARGET 2 Stool Consist. Daily (FDA) 0.0009 (1.24, 2.33) 1.70 TARGET 1 0.0058 (1.09, 1.64) 1.33 Combined 0.0298 (1.03, 1.83) 1.37 TARGET 2 0.0725 (0.98, 1.75) 1.31 TARGET 1 Ab Pain Daily (FDA) 0.0118 (1.06, 1.61) 1.31 Combined 0.0435 (1.01, 1.81) 1.35 TARGET 2 IBS Ab Pain Daily 0.0495 (1.00, 1.83) 1.35 TARGET 1 <0.0001 (1.24, 1.89) 1.53 Combined 0.0008 (1.24, 2.25) 1.67 TARGET 2 0.0103 (1.10, 2.04) 1.50 TARGET 1 IBS Bloating Daily 0.0003 (1.20, 1.83) 1.48 Combined 0.0127 (1.09, 1.99) 1.47 TARGET 2 SGA-IBS Daily 0.0025 (1.18, 2.18) 1.60 TARGET 1 0.0011 (1.15, 1.75) 1.42 Combined 0.0031 (1.16, 2.09) 1.56 TARGET 2 0.1042 (0.95, 1.73) 1.28 TARGET 1 0.0007 (1.17, 1.77) 1.44 Combined 0.0053 (1.13, 2.03) 1.52 TARGET 2 SGA-IBS Weekly 0.0477 (1.00, 1.82) 1.35 TARGET 1 0.0014 (1.14, 1.72) 1.40 Combined 0.0141 (1.08, 1.92) 1.44 TARGET 2 0.0396 (1.01, 1.83) 1.36 TARGET 1 Ab Pain & Stool Daily (FDA) IBS Bloating Weekly p-value (95% CI) Odds Ratio Study Efficacy Outcome <0.0001 (1.27, 1.97) 1.58 Combined 0.0114 (1.09, 2.00) 1.48 TARGET 2 Stool Consist. Daily (FDA) 0.0009 (1.24, 2.33) 1.70 TARGET 1 0.0058 (1.09, 1.64) 1.33 Combined 0.0298 (1.03, 1.83) 1.37 TARGET 2 0.0725 (0.98, 1.75) 1.31 TARGET 1 Ab Pain Daily (FDA) 0.0118 (1.06, 1.61) 1.31 Combined 0.0435 (1.01, 1.81) 1.35 TARGET 2 IBS Ab Pain Daily 0.0495 (1.00, 1.83) 1.35 TARGET 1 <0.0001 (1.24, 1.89) 1.53 Combined 0.0008 (1.24, 2.25) 1.67 TARGET 2 0.0103 (1.10, 2.04) 1.50 TARGET 1 IBS Bloating Daily 0.0003 (1.20, 1.83) 1.48 Combined 0.0127 (1.09, 1.99) 1.47 TARGET 2 SGA-IBS Daily 0.0025 (1.18, 2.18) 1.60 TARGET 1 0.0011 (1.15, 1.75) 1.42 Combined 0.0031 (1.16, 2.09) 1.56 TARGET 2 0.1042 (0.95, 1.73) 1.28 TARGET 1 0.0007 (1.17, 1.77) 1.44 Combined 0.0053 (1.13, 2.03) 1.52 TARGET 2 SGA-IBS Weekly 0.0477 (1.00, 1.82) 1.35 TARGET 1 Key Secondary Primary Other Secondary FDA Proposed 0.0 0.5 1.0 1.5 2.0 2.5 |
![]() 32 Inter-Item Correlation of Convergent Validity Results Regardless of Treatment Assignment 0.43 0.90 0.71 0.55 0.77 0.58 Daily Ab Pain (FDA) --- 0.58 0.41 0.37 0.49 0.41 Daily Stool Form (FDA) --- 0.66 0.54 0.72 0.60 Daily Ab Pain & Stool (FDA) --- 0.62 0.83 0.55 Daily Bloating --- 0.58 0.78 Weekly Bloating --- 0.62 Daily SGA IBS Daily Stool Form (FDA) Daily Ab Pain & Stool (FDA) Daily Bloating Weekly Bloating Daily SGA IBS Weekly SGA IBS Spearman’s rank correlation of 0.4 indicates convergent validity and a correlation of < 0.3 indicates divergent validity |
![]() 33 Rifaximin Safety Profile n (%) n (%) 0 6 (1.0) 2 (0.3) 178 (28.5) Rifaximin (n=624) 0 Deaths 6 (0.9) AEs resulting in discontinuation SAEs Any AEs 8 (0.8) 188 (29.7) Placebo (n=634) • Common AEs: headache (rifaximin 4%, placebo 4%), abdominal pain (3%, 3%), nausea (3%, 2%), nasopharyngitis (1%, 3%) and upper respiratory tract infection (1%, 2%) • Most AEs were mild or moderate in intensity • No AEs of C. difficile associated diarrhea or ischemic colitis Combined Data from TARGET 1 and TARGET 2 |
![]() 34 Conclusions TREATMENT EFFICACY • Rifaximin 550 mg TID for 14 days produced a significant improvement in non-constipation IBS in TARGET 1 and TARGET 2 for the following endpoints: – Primary- SGA-IBS – Key and other secondary endpoints- IBS-related bloating, abdominal pain, stool consistency – New FDA proposed endpoint- Abdominal pain and stool consistency DURABLE RELIEF • Response to rifaximin was sustained for up to 3 months SAFETY • No differences in reported adverse events were observed between rifaximin and placebo |
![]() 35 DDW2010 Investor Event Agenda Introduction and Background Bill Forbes, Pharm.D. Executive Vice President, Research and Development and Chief Development Officer Salix Pharmaceuticals TARGET 1 & 2 - Efficacy and Safety of Rifaximin 550 mg TID in the Treatment of Patients with Non–Constipation IBS Mark Pimentel, MD, FRCP (C) Associate Professor of Medicine, Geffen School of Medicine at UCLA Director, GI Motility Program, Cedars–Sinai Medical Center Question and Answer Philip Schoenfeld, MD, MSED, MSc Associate Professor, Department of Internal Medicine Division of Gastroenterology, The University of Michigan Closing Remarks Carolyn J. Logan President & CEO, Salix Pharmaceuticals |
![]() 36 DDW2010 Investor Event Agenda Introduction and Background Bill Forbes, Pharm.D. Executive Vice President, Research and Development and Chief Development Officer Salix Pharmaceuticals TARGET 1 & 2 - Efficacy and Safety of Rifaximin 550 mg TID in the Treatment of Patients with Non–Constipation IBS Mark Pimentel, MD, FRCP (C) Associate Professor of Medicine, Geffen School of Medicine at UCLA Director, GI Motility Program, Cedars–Sinai Medical Center Question and Answer Philip Schoenfeld, MD, MSED, MSc Associate Professor, Department of Internal Medicine Division of Gastroenterology, The University of Michigan Closing Remarks Carolyn J. Logan President & CEO, Salix Pharmaceuticals |