8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 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 3, 2010

SALIX PHARMACEUTICALS, LTD.

(Exact name of registrant as specified in its charter)

Delaware

(State or other jurisdiction of incorporation)

000-23265	94-3267443
(Commission File Number)	(IRS Employer ID Number)

1700 Perimeter Park Drive, Morrisville, North Carolina 27560

(Address of principal executive offices)                                         (Zip Code)

Registrant’s telephone number, including area code (919) 862-1000

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:

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

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

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

¨ 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 3, 2010, William P. Forbes, PharmD, of Salix Pharmaceuticals, Ltd., conducted a meeting at the Digestive Disease Week 2010 conference, beginning at 9:00 p.m. Central Time. A webcast of the meeting is posted on the Company’s website at www.Salix.com. The slides included in Dr. Forbes’ presentation are attached hereto as Exhibit 99.1 and are incorporated herein in their entirety by reference.

The information in this Form 8-K (including Exhibit 99.1) shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933 or the Exchange Act, except as expressly set forth by specific reference in such a filing.

Item 9.01. Financial Statements and Exhibits.

(d) Exhibits

Exhibit No.	Description
99.1	Slides presented at a meeting held during the Digestive Disease Week 2010 Conference on May 3, 2010.

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 thereunto duly authorized.

	SALIX PHARMACEUTICALS, LTD.
Date: May 4, 2010
	/s/  ADAM C. DERBYSHIRE
	Adam C. Derbyshire
	Executive Vice President and Chief Financial Officer

EX-99.1

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