Salix Pharmaceuticals Announces FDA Acceptance for Filing and Priority Review Designation for Rifaximin NDA for the Maintenance of Remission of Hepatic Encephalopathy
RALEIGH, NC, August 24, 2009 – Salix Pharmaceuticals, Ltd. (NASDAQ:SLXP) today announced
the Food and Drug Administration (FDA) has accepted for filing and designated for Priority Review the Company's New Drug Application (NDA) for rifaximin
tablets 550 mg for the maintenance of remission of hepatic
encephalopathy (HE). Additionally, the FDA has informed the Company of its plan to schedule an Advisory Committee meeting in late February 2010
to discuss the application.
A Priority Review classification is granted to drugs offering major advances in treatment, or providing a treatment where no adequate therapy exists.
Based on this classification, the FDA has issued an action date of December 24, 2009 under the Prescription Drug User Fee Act (PDUFA). However, the convening
of an Advisory Committee in late February 2010 signals the December 24, 2009 action date will be delayed.
"We are pleased with the FDA's acceptance for filing of the rifaximin NDA and their decision to grant Priority Review for our application," stated Bill
Forbes, Pharm.D., Senior Vice President and Chief Development Officer, Salix Pharmaceuticals. "This review classification signals that the FDA considers
that rifaximin has the potential to provide a significant advance in the treatment of hepatic encephalopathy. We are not surprised at the FDA's
decision to convene an Advisory Committee to gain an independent recommendation from outside experts regarding rifaximin due to the fact that, if
approved, rifaximin will be the first new option approved for the management of HE in over 30 years. We believe the availability of rifaximin has
the potential to change the treatment paradigm for HE. Today's news marks a milestone for Salix, rifaximin and patients suffering from this serious
condition."
Currently Salix estimates the U.S. commercial opportunity represented by the HE market is approximately $600 million. Hepatic encephalopathy occurs frequently
in patients with cirrhosis as a result of their end–stage liver disease. Typically the cirrhosis is caused by a number of factors, such as alcohol
and/or drug abuse, chronic viral hepatitis and autoimmune disease. Cirrhosis is a leading cause of death in the United States.1 The
number of cases of liver disease in the United States and around the world is rapidly increasing, with more than 7 million people in the United States
being diagnosed with chronic liver disease.2 There are reported to be more than 100,000 patients in the United States with overt HE.3
Rifaximin has been granted Orphan Drug designation by the FDA for use in hepatic encephalopathy. Salix believes this designation will provide seven years
of marketing exclusivity in the United States if rifaximin gains approval from the FDA for HE.
About Hepatic Encephalopathy
Hepatic encephalopathy (HE) is a neurological disorder caused by chronic liver failure resulting in cognitive, psychiatric and motor impairments.4 The
condition encompasses a wide spectrum of often reversible neuropsychiatric abnormalities caused by the inability of the liver to remove toxic products
in the gut, most notably ammonia–producing bacteria.5 When toxins reach the central nervous system, this condition can result in symptoms
ranging in severity from mild cerebral function deficits to coma and characterized by disruption in sleep patterns, changes in personality and intellectual
capacity, high blood ammonia levels, altered neuromuscular activity and electroencephalogram (EEG) abnormalities.6,7
About XIFAXAN® (rifaximin)
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 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 (550 mg) is under investigation in the United States as a treatment for irritable bowel syndrome. 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., 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. METOZOLVTM ODT (metoclopramide), crofelemer, budesonide foam and rifaximin
for additional indications are under development.
1Miniño AM, Heron MP, Murphy SL, Kochanek KD. Deaths: Final data for 2004. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/nchs/data/nvsr/nvsr55/nvsr55_19.pdf.
Updated October 10, 2007. Accessed January 20, 2008.
2Everhart JE, editor. The burden of digestive diseases in the United States. US Department of Health and Human Services, Public Health Service, National
Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Washington, DC: US Government Printing Office, 2008; NIH
Publication No. 09–6443 [pp. 111–114]
3Poordad FF. Review Article: The Burden of Hepatic Encephalopathy. Alimentary Pharmacology & Therapeutics. 25 Supplement 1:3–9, February 2007.
4National Institute on Alcoholism and Alcohol Abuse of the National Institutes of Health. Hepatic Encephalopathy. September 29, 2004. Available at:
http://pubs.niaaa.nih.gov/publications/arh27-3/240-246.htm.
5Blei AT, Co'rdoba J and The Practice Parameters Committee of the American College of Gastroenterology. Hepatic Encephalopathy. Practice Guidelines. Vol.
96, No. 7, 2001.
6IBID
7Abou–Assi S. Vlahcevic ZR. Hepatic encephalopathy. Metabolic consequence of cirrhosis often is reversible. Postgraduate Medicine. 109(2):52–4,
57–60, 63–5 passim, 2001 Feb.
For full prescribing information on Salix products, please visit www.salix.com or
contact the Company at 919–862–1000.
Salix trades on the NASDAQ Global Select Market under the ticker symbol "SLXP".
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
in 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.