Salix Pharmaceuticals, Ltd. (NASDAQ:SLXP) announced today that on August
29, 2014, it submitted its response to the March 7, 2011, Food and Drug
Administration (FDA) Complete Response Letter (CRL) regarding the
Company’s supplemental New Drug Application (sNDA) for XIFAXAN® 550 mg
tablets for the proposed indication of the treatment of irritable bowel
syndrome with diarrhea or IBS-D. Upon receipt of Salix’s response, the
FDA will have six months to issue a response.
“We are pleased that the outcome of TARGET 3 provides both prospective
controlled data to support the efficacy and safety of repeat treatment
with rifaximin,” stated Bill Forbes, PharmD, Executive Vice President,
Medical, Research and Development and Chief Development Officer, Salix.
“Beyond corroborating the efficacy and safety results of TARGET 1 and
TARGET 2, the results of TARGET 3 provide important microbiome as well
as culture and susceptibility results that provide additional support of
the safety of repeat treatment with rifaximin. These compelling data
should provide adequate information for the basis of the product
labeling used to guide patients and their health care providers on how
to safely and most effectively administer repeat treatment of rifaximin
in patients with recurrence in their symptoms of IBS-D. We look forward
to continuing our collaborative discussion with the FDA with our
response in this submission.”
During its original review of Salix’s sNDA, the FDA determined it is
important in a chronic condition such as IBS to have information about
how a product that is intended for short course administration in order
to confer prolonged benefit should be administered beyond the first
cycle of use once symptoms reappear. In addition, the FDA determined
that patients and their health care providers should have information on
the safety and effectiveness of this retreatment. The FDA conveyed this
information to Salix in a March 7, 2011, CRL. Over the past three and
one-half years, Salix and the FDA worked collaboratively to develop a
study protocol (TARGET 3) intended to collect prospective controlled
data to support repeat treatment with rifaximin in order to obtain
adequate information for product labeling to guide patients and their
health care providers on how to safely and most effectively administer
repeat treatment of rifaximin in patients with IBS. This collaboration
with the FDA also included a publicly held meeting with the
Gastrointestinal Drugs Advisory Committee on November 16, 2011.
TARGET 3 – DESIGN
In February 2012 Salix initiated TARGET 3 – a Phase 3 study to evaluate
the efficacy and safety of repeat treatment with rifaximin 550 mg TID
(three times daily) for 14 days in subjects with IBS-D who responded to
an initial treatment course with rifaximin 550 mg TID for 14 days. The
study screened subjects with IBS-D, treated them with rifaximin and
followed those that responded to this initial course of therapy until
their symptoms recurred, at which time they underwent double-blind
randomization to either another course of rifaximin 550 mg TID for 14
days or matching placebo. Additionally, subjects continued to be
followed to assess durability of their response and underwent an
additional course of previously-assigned double-blind therapy. TARGET
3’s primary endpoint was the proportion of subjects who responded to
repeat treatment in both IBS-related abdominal pain and stool
consistency during the 4 week treatment-free follow-up period (Primary
Evaluation Period, or PEP) in the Double Blind Repeat (or DBR) Treatment
Phase as compared to the placebo treated group. Safety assessments
included evaluation for resistance and changes in the gut microbiome.
Enrollment in the double blind portion of TARGET 3 was completed in
January 2014. TARGET 3 randomized 636 subjects (adults with IBS-D) into
the double blind retreatment phase of the study.
TARGET 3 - RESULTS
Primary Endpoint
On July 1, 2014, Salix reported a statistically significant greater
proportion of rifaximin treated subjects (as compared to placebo)
responded to repeat treatment as assessed by the composite primary
endpoint of IBS-related abdominal pain and stool consistency during the
4 week treatment-free follow-up period (Primary Evaluation Period, or
PEP) in the Double Blind Repeat Treatment Phase.
Key Secondary Endpoints
On August 11, 2014, Salix reported a statistically significant greater
proportion of rifaximin treated subjects (as compared to placebo)
experienced relief of symptoms during the Primary Evaluation Period
(PEP) in the first repeat treatment phase and the avoidance of
subsequent symptom recurrence (in subjects with symptom relief) during
the: Double-Blind Phase of the Study (Key Secondary Efficacy Endpoint
Number 1: Response type – durable and maintained) and the First
Double-Blind Repeat Treatment and follow-up (Key Secondary Efficacy
Endpoint Number 2: Response type – durable).
Safety Data
On August 11, 2014, Salix reported topline results from the analysis of
the effects of rifaximin on the microbiome, culture and susceptibility
on the gut microbiota. The analysis revealed no disturbance of fecal
microbiota in subjects taking repeat courses of rifaximin as compared to
subjects taking a single course of rifaximin followed by placebo for the
remainder of the trial. Additionally, results of the culture and
susceptibility testing demonstrated no evidence of cross-resistance to
non-rifamycin antibiotics in isolates grown from either stool or skin
swab cultures. Importantly, repeat treatment courses of rifaximin do not
appear to predispose patients to the emergence of potentially pathogenic
bacteria in the stool or on the skin.
About XIFAXAN 550 mg
Indication:
XIFAXAN® (rifaximin) 550 mg tablets are indicated for reduction in risk
of overt hepatic encephalopathy (HE) recurrence in patients ≥ 18 years
of age.
Important Safety Information about XIFAXAN 550 mg
XIFAXAN® (rifaximin) 550 mg tablets are contraindicated in patients with
a hypersensitivity to rifaximin, any of the rifamycin antimicrobial
agents, or any of the components in XIFAXAN. Hypersensitivity reactions
have included exfoliative dermatitis, angioneurotic edema, and
anaphylaxis.
Clostridium difficile-associated diarrhea (CDAD) has been
reported with use of nearly all antibacterial agents, including XIFAXAN,
and may range in severity from mild diarrhea to fatal colitis. Treatment
with antibacterial agents alters the normal flora of the colon which may
lead to overgrowth of C. difficile. If CDAD is suspected or
confirmed, ongoing antibiotic use not directed against C. difficile may
need to be discontinued.
There is increased systemic exposure in patients with more severe
hepatic dysfunction. The clinical trials were limited to patients with
MELD scores < 25. Therefore, caution should be exercised when
administering XIFAXAN to patients with severe hepatic impairment
(Child-Pugh C).
Concomitant administration of drugs that are P-glycoprotein (P-gp)
inhibitors with XIFAXAN can substantially increase the systemic exposure
to XIFAXAN. Caution should be exercised when concomitant use of XIFAXAN
and a P-gp inhibitor such as cyclosporine is needed. In patients with
hepatic impairment, a potential additive effect of reduced metabolism
and concomitant P-gp inhibitors may further increase the systemic
exposure to XIFAXAN.
Based on animal data, XIFAXAN may cause fetal harm. Discontinue in
nursing mothers after taking into account the importance of the drug to
the mother.
The most common adverse reactions occurring in ≥ 10% of patients and at
a higher incidence than placebo in the clinical study were peripheral
edema (15%), nausea (14%), dizziness (13%), fatigue (12%), and ascites
(11%).
Xifaxan 550 mg is licensed by Alfa Wassermann S.p.A. to Salix
Pharmaceuticals, Inc.
Please see complete Prescribing Information for XIFAXAN.
About Salix
Salix Pharmaceuticals, Ltd., headquartered in Raleigh, North Carolina,
develops and markets prescription pharmaceutical products and medical
devices for the prevention and treatment of gastrointestinal diseases.
Salix’s strategy is to in-license late-stage or marketed proprietary
therapeutic products, complete any required development and regulatory
submission of these products, and commercialize them through the
Company’s 500-member specialty sales force.
Salix markets XIFAXAN® (rifaximin) tablets 200 mg and 550 mg,
MOVIPREP® (PEG 3350, sodium sulfate, sodium chloride,
potassium chloride, sodium ascorbate and ascorbic acid for oral
solution, 100 g/7.5 g/2.691 g/1.015 g/5.9 g/4.7 g), OSMOPREP®
(sodium phosphate monobasic monohydrate, USP, and sodium phosphate
dibasic anhydrous, USP) Tablets, APRISO® (mesalamine)
extended-release capsules 0.375 g, UCERIS® (budesonide)
extended release tablets, for oral use, GIAZO® (balsalazide
disodium) tablets, COLAZAL® (balsalazide disodium) Capsules,
GLUMETZA® (metformin hydrochloride extended-release tablets)
500 mg and 1000 mg, ZEGERID® (omeprazole/sodium bicarbonate)
Powder for Oral Suspension, ZEGERID® (omeprazole/sodium
bicarbonate) Capsules, METOZOLV® ODT (metoclopramide
hydrochloride), RELISTOR® (methylnaltrexone bromide)
Subcutaneous Injection, FULYZAQ® (crofelemer) delayed-release
tablets, SOLESTA®, DEFLUX®, PEPCID® (famotidine)
for Oral Suspension, DIURIL® (chlorothiazide) Oral
Suspension, 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, CYCLOSET®
(bromocriptine mesylate) tablets, FENOGLIDE® (fenofibrate)
tablets. UCERIS (budesonide) rectal foam, RELISTOR®,
encapsulated bowel preparation and rifaximin for additional indications
are under development.
For full prescribing information and important safety information on
Salix products, including BOXED WARNINGS for OSMOPREP, AZASAN, GLUMETZA
and METOZOLV, 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.
Salix trades on the NASDAQ Global Select Market under the ticker symbol
“SLXP”.
For more information, please visit our website at www.salix.com
or contact Salix at 919-862-1000. Follow us on Twitter (@SalixPharma)
and Facebook (www.facebook.com/SalixPharma).
Information on our Twitter feed, Facebook page and website is not
incorporated in our filings with the SEC.
Salix Disclosure Notice
As previously announced on July 8, 2014, Salix, Cosmo Pharmaceuticals
S.p.A. and Irish domiciled Cosmo Technologies Limited entered into an
Agreement and Plan of Merger and Reorganization, pursuant to which a
subsidiary of Cosmo Technologies Limited will merge with and into Salix,
with Salix as the surviving entity, and Salix will become an indirect,
wholly-owned subsidiary of Cosmo Technologies Limited, which will change
its name to Salix Pharmaceuticals, plc.
Please Note: The statements provided herein that are not historical
facts are or might constitute projections and other forward-looking
statements regarding future events. Although we believe the
expectations reflected in such forward-looking statements are based on
reasonable assumptions, our expectations might not be attained. Forward-looking
statements are just predictions and are subject to known and unknown
risks and uncertainties that could cause actual events or results to
differ materially from expected results. Factors that could cause
actual events or results to differ materially from those described
herein include, among others: uncertainty regarding the Food and Drug
Administration’s review of and response to the Company’s response to the
Food and Drug Administration’s complete response letter regarding the
Company’s supplemental New Drug Application for XIFAXAN (rifaximin) 550
mg tablets, including the risk that XIFAXAN will not be approved for
sale or, if approved, will not be commercially successful; uncertainties
as to the ability to successfully complete the proposed Cosmo
transaction in accordance with its terms and in accordance with the
expected schedule; the possibility that competing offers will be made;
the possibility that various closing conditions for the proposed Cosmo
transaction may not be satisfied or waived, including that a
governmental entity may prohibit or refuse to grant any approval
required for the consummation of the proposed transaction; the
unpredictability of the duration and results of regulatory review of New
Drug Applications, Biologics License Agreements, and Investigational
NDAs; generic and other competition in an increasingly global industry;
litigation and the possible impairment of, or inability to obtain,
intellectual property rights and the costs of obtaining such rights from
third parties in an increasingly global industry; the cost, timing and
results of clinical trials and other development activities involving
pharmaceutical products; post-marketing approval regulation, including
the ongoing Department of Justice investigation of Salix’s marketing
practices; market acceptance for approved products; revenue recognition
and other critical accounting policies; the need to acquire new
products; changes in tax laws or interpretations thereof; general
economic and business conditions; and other factors. Readers are
cautioned not to place undue reliance on the forward-looking statements
included herein, which speak only as of the date hereof. Salix
does not undertake to update any of these statements in light of new
information or future events, except as required by law. The
reader is referred to the documents that Salix files from time to time
with the SEC.
Copyright Business Wire 2014