Salix Pharmaceuticals Reports Concurrence with FDA on Content and Format of the Pending Rifaximin NDA in the Treatment of Non-Constipation Irritable Bowel Syndrome
Previously Agreed Upon Endpoints for Phase 3 Trials TARGET 1 and TARGET 2 Confirmed
NDA Submission Continues to be on Track for First Half 2010
RALEIGH, NC, December 10, 2009 – Salix Pharmaceuticals, Ltd. (NASDAQ:SLXP) today
reported that the Company held a pre-NDA meeting on December
8, 2009 with the FDA to discuss the Company's proposed new drug application (NDA) for rifaximin in the treatment of patients with non-constipation
irritable bowel syndrome (non-C IBS).
The purpose of the meeting was to discuss the completion of the Company's non-C IBS Development Program, the results of two Phase 3 trials, TARGET
1 and TARGET 2, and to reach agreement on the content and format of the Company's pending NDA.
"We are pleased with the results of our discussions with the FDA regarding our completed Phase 3 trials and our proposed NDA for rifaximin in the treatment
of non-C IBS," stated Bill Forbes, Pharm.D., Senior Vice President Research and Development and Chief Development Officer, Salix. "During
our meeting, we were able to review the prior agreements reached with the Gastrointestinal Division. As expected, the agreements, including the protocol-specified
primary and key secondary endpoints used in TARGET 1 and TARGET 2 as the basis of the review for marketing approval of rifaximin
in non-C IBS, were confirmed. It has been known that the FDA's Division of Gastroenterology Products (DGP), along with assistance from the
Study Endpoint and Labeling Development (SEALD) Team, have been developing a new guidance for the use of endpoints in IBS clinical trials. The Phase
3 trials were designed, in consultation with the Division, to investigate the utility of rifaximin in non-C IBS by assessing adequate relief
of IBS symptoms, adequate relief of IBS-related bloating and other endpoints such as abdominal pain and stool consistency. We are pleased
that a clear regulatory pathway for the review and potential approval of rifaximin in non-C IBS has been provided. We continue to target submission
of the NDA during the first half of 2010."
About TARGET 1 and TARGET 2
TARGET 1 and TARGET 2 (T-Targeted, non-systemic; A-Antibiotic; R-Rifaximin; G-Gut-selective; E-Evaluation of;
T-Treatment for non-C IBS) were designed to assess the clinical efficacy and safety of a 550 mg TID dosing regimen of rifaximin (1650 mg/day)
compared with placebo in a broad population comprised of males and females 18 years of age and older who have been diagnosed with non-constipation
IBS, e.g., diarrhea-predominant IBS or alternating IBS. The primary efficacy endpoint of TARGET 1 and TARGET 2 is the proportion of subjects who achieve adequate relief of IBS symptoms for at least 2 weeks during the first 4 weeks of the 10-week follow-up phase. The
two 600-subject trials were conducted simultaneously in approximately 180 study centers throughout the United States and Canada. Subjects received
rifaximin or placebo (1:1 randomization) for 14 days and then were followed for 10 weeks for study duration of 12 weeks.
About IBS
Among one of the most common chronic conditions, irritable bowel syndrome (IBS) affects approximately 15% of adults in the United States. IBS includes
altered bowel habits with abdominal pain and discomfort. Among other contributors, recent science has shown that alterations in gut flora / bacteria
have been identified as a potentially important contributor to the pathophysiology of IBS. Small intestinal bacterial overgrowth, a condition associated
with excessive numbers of bacteria in the small intestine, may underlie some of the gastrointestinal symptoms associated with IBS. The Company
now estimates the U.S. commercial opportunity represented by the non-constipation IBS market to be approximately $7 billion in peak year.
About XIFAXAN® (rifaximin)
Rifaximin is a gut-selective antibiotic with negligible systemic absorption (<0.4%) and broad-spectrum activity in vitro against both gram-positive
and gram-negative pathogens. Rifaximin has a similar tolerability profile to that of placebo.
Rifaximin tablets 200 mg, which Salix markets in the United States under the trade name XIFAXAN® (rifaximin) tablets 200 mg, currently is
approved for the treatment of patients, 12 years of age or older, with travelers' diarrhea (TD) caused by non-invasive strains of Escherichia
coli. XIFAXAN (rifaximin) is a gut-selective antibiotic with negligible systemic absorption (<0.4%) and broad-spectrum activity
in vitro against both gram-positive and gram-negative pathogens. Rifaximin has a similar tolerability profile to that of placebo and has
activity against the most common TD pathogens. XIFAXAN should not be used in patients with diarrhea complicated by fever or blood in the stool or
diarrhea due to pathogens other than Escherichia coli. XIFAXAN should be discontinued if diarrhea symptoms get worse or persist more than 24-48
hours and alternative antibiotic therapy should be considered. In clinical trials, XIFAXAN was generally well tolerated. The most common side
effects (vs. placebo) were flatulence 11.3% (versus 19.7%), headache 9.7% (versus 9.2%), abdominal pain 7.2% (versus 10.1 %) and rectal tenesmus 7.2%
(versus 8.8%).
Rifaximin has been used in Italy for 24 years and is approved in 33 countries. Salix acquired rights to market rifaximin in North America from Alfa Wassermann
S.p.A. in Bologna, Italy. Alfa Wassermann markets rifaximin in Italy under the trade name Normix®.
About Salix Pharmaceuticals
Salix Pharmaceuticals, Ltd., headquartered in Raleigh, NC, develops and markets prescription pharmaceutical products for the treatment of gastrointestinal
diseases. Salix's strategy is to in-license late-stage or marketed proprietary therapeutic drugs, complete with any required development
and regulatory submission of these products, and market them through the Company's gastroenterology specialty sales and marketing team.
Salix also markets OSMOPREP® (sodium phosphate monobasic monohydrate, USP and sodium phosphate dibasic anhydrous, USP) Tablets, MOVIPREP®
(PEG 3350, Sodium Sulfate, Sodium Chloride, Potassium Chloride, Sodium Ascorbate and Ascorbic Acid for Oral Solution), VISICOL®
(sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP) Tablets, APRISO™ (mesalamine)
extended-release capsules 0.375 g., METOZOLVTM ODT (metoclopramide HCl), PEPCID® (famotidine) for Oral Suspension, Oral Suspension
DIURIL® (Chlorothiazide), AZASAN® Azathioprine Tablets, USP, 75/100 mg, ANUSOL-HC® 2.5% (Hydrocortisone
Cream, USP), ANUSOL-HC® 25 mg Suppository (Hydrocortisone Acetate), PROCTOCORT® Cream (Hydrocortisone
Cream, USP) 1% and PROCTOCORT® Suppository (Hydrocortisone Acetate Rectal Suppositories) 30 mg. Crofelemer, budesonide foam and rifaximin for additional indications are under development.
For full prescribing information and important safety information, including BOXED WARNINGS for VISICOL, OSMOPREP and METOZOLV, on Salix products, please
visit www.salix.com where the Company promptly posts press releases,
SEC filings and other important information or contact the Company at 919 862-1000.
For more information, please visit our Web site at www.salix.com or contact the Company at 919-862-1000. Information
on our Web site is not incorporated into our SEC filings.
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APRISO™ is a locally-acting aminosalicylate indicated for the maintenance of remission of ulcerative colitis in patients 18 years and older.
APRISO is contraindicated in patients with hypersensitivity to salicylates, aminosalicylates, or to any of the components of APRISO capsules.
The recommended dose of APRISO is four 0.375 g capsules once daily in the morning (1.5 g/day) with or without food. Because dissolution of the coating of APRISO
granules depends on pH, APRISO should not be coadministered with antacids. Patients with phenylketonuria should be aware that APRISO contains aspartame,
equivalent to 0.56 mg of phenylalanine. In two well-controlled clinical trials, the most common treatment-related adverse events occurring in at least 3%
of adult patients taking 1.5 g/day of APRISO were headache (11% vs. 8% for placebo), diarrhea (8% vs. 7% for placebo), upper abdominal pain (5% vs 3% for placebo),
nausea (4% vs 3% for placebo), nasopharyngitis (4% vs 3% for placebo), influenza and influenza-like illness (4% vs 4% for placebo) and sinusitis (3% vs 3% for placebo).
For complete Prescribing Information, please click here.
MoviPrep® (PEG-3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid for oral solution) is indicated for cleansing of the
colon as a preparation for colonoscopy in adults 18 years of age or older. MoviPrep is contraindicated in patients who have had a severe hypersensitivity reaction
to any of its components. MoviPrep should be used with caution in patients using concomitant medications that increase the risk of electrolyte abnormalities, in patients with known or suspected hyponatremia,
severe ulcerative colitis, ileus, gastrointestinal obstruction or perforation, gastric retention, toxic colitis, toxic megacolon, or glucose-6-phosphate dehydrogenase deficiency. In clinical trials, abdominal
distention, anal discomfort, thirst, nausea, and abdominal pain were the most common adverse reactions to MoviPrep administration. MoviPrep contains a maximum of 2.33 mg of phenylalanine per treatment.
Consult with your physician to see if this product is right for you.
For complete Prescribing Information, please click here.
Important Safety Information about OsmoPrep
There have been rare, but serious reports of acute phosphate nephropathy in patients who received oral sodium phosphate products for colon cleansing prior
to colonoscopy. Some cases have resulted in permanent impairment of renal function and some patients required long–term dialysis. While some
cases have occurred in patients without identifiable risk factors, patients at increased risk of acute phosphate nephropathy may include those with
increased age, hypovolemia, increased bowel transit time (such as bowel obstruction), active colitis, or baseline kidney disease, and those using
medicines that affect renal perfusion or function (such as diuretics, angiotensin converting enzyme [ACE] inhibitors, angiotensin receptor blockers
[ARBs], and possibly nonsteroidal anti–inflammatory drugs [NSAIDs]).
It is important to use the dose and dosing regimen as recommended (PM/AM split dose).
Please see accompanying brief summary of Prescribing Information for OsmoPrep, including
BOXED WARNINGS.
OsmoPrep® (sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP) Tablets are indicated for cleansing
of the colon as a preparation for colonoscopy in adults 18 years of age or older. Considerable caution should be advised before OsmoPrep is used in
patients with severe renal insufficiency, congestive heart failure, ascites, unstable angina, gastric retention, ileus, severe chronic constipation,
bowel perforation, toxic megacolon, gastric bypass or stapling surgery, or hypomotility syndrome. Use with caution in patients with impaired renal
function, patients with a history of seizures or at higher risk of seizure, patients with higher risk of cardiac arrhythmias, known or suspected electrolyte
disturbances (such as dehydration), or people taking drugs that affect electrolyte levels. Patients with electrolyte abnormalities such as
hypernatremia, hyperphosphatemia, hypokalemia, or hypocalcemia should have their electrolytes corrected before treatment with OsmoPrep.
OsmoPrep is contraindicated in patients with a known allergy or hypersensitivity to sodium phosphate salts or any of its ingredients, and in patients with
biopsy–proven acute phosphate nephropathy. In clinical trials, the most commonly reported adverse reactions (reporting frequency >3%) were
abdominal bloating, nausea, abdominal pain, and vomiting. It is recommended that patients receiving OsmoPrep be advised to adequately hydrate before,
during, and after the use of OsmoPrep.
For complete Prescribing Information, please click here.
SAFETY CONSIDERATIONS
Xifaxan® (rifaximin) Tablets are indicated for the treatment of patients (≥12 years of age) with travelers’ diarrhea caused by noninvasive strains of
Escherichia coli. Xifaxan should not be used in patients with diarrhea complicated by fever or blood in the stool or diarrhea due to pathogens other than Escherichia coli. Xifaxan should be
discontinued if diarrhea symptoms get worse or persist more than 24-48 hours and alternative antibiotic therapy should be considered. Escherichia coli has been shown to develop resistance to rifaximin in vitro. However, the clinical significance of such an effect has not been studied.
In clinical trials, Xifaxan was generally well tolerated. The most common side effects (vs. placebo) were flatulence 11.3% (vs. 19.7%), headache 9.7% (vs. 9.2%), abdominal pain 7.2% (vs. 10.1%), rectal tenesmus 7.2%
(vs. 8.8%), defecation urgency 5.9% (vs. 9.2%) and nausea 5.3% (vs. 8.3%).
For complete Prescribing Information, please click here.