Salix Pharmaceuticals, Ltd. (NASDAQ:SLXP) today announced the topline
results from the analysis of the microbiome, culture and susceptibility,
and two key secondary efficacy endpoints from data collected in TARGET 3
– a Phase 3 randomized, double-blind, placebo-controlled study to
evaluate the efficacy and safety of repeat treatment with rifaximin 550
mg TID (three times daily) for 14 days in subjects with irritable bowel
syndrome with diarrhea, or IBS-D, who respond to an initial treatment
course with rifaximin 550 mg TID for 14 days.
The effects of rifaximin on the gut microbiota in the IBS-D repeat
treatment study, TARGET 3, were evaluated by two methods: traditional
culture techniques and next-generation gene sequencing of stool samples
collected from approximately 100 randomly selected subjects in the
trial. Skin swabs were also obtained from an additional 113 randomly
selected subjects and cultured for Staphylococcus bacteria.
Using next-generation 16S rRNA gene sequencing methods, we generated
approximately 2.2 billion base pairs from stool samples collected over
the course of the study from approximately 100 randomly selected
subjects. Our data reveal no disturbance of fecal microbiota, based on
both diversity and Bray-Curtis similarity measures, 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.
Results of the culture and susceptibility testing demonstrate 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 (e.g., C. difficile,
Enterococcus, or Staphylococcus) in the stool or on the skin. As would
be expected, given the high concentration of rifaximin achieved in the
stool, transient changes in the rifaximin minimum inhibitory
concentrations (MICs), a measure of microbial sensitivity to an
antibiotic, were observed in some of the normal flora but these changes
were reversible over time. A very small number of C. difficile isolates
were identified in stool samples at a rate consistent with literature
reports of asymptomatic carriers in the general population, and none of
these isolates demonstrated rifaximin resistance.
Efficacy: The company previously disclosed topline efficacy results in
both the July 1, 2014 press release as well as the July 9, 2014 Investor
Day. Today’s press release discloses the results of two of the Key
Secondary Efficacy Endpoints included in TARGET 3 in support of the
Primary Efficacy Endpoint.
These Key Secondary Endpoints evaluated 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): Proportion that
responded to the composite FDA Endpoint of relief in both IBS-related
Abdominal Pain AND Stool Consistency during the PEP in the first
repeat double-blind, placebo controlled treatment phase AND continued
to respond without recurrence through the end of Week 6 following the
second repeat double-blind, placebo controlled treatment. The results
indicate a significantly greater proportion of rifaximin-treated
subjects met this endpoint as compared to placebo-treated subjects
(p=0.0068).
-
First Double-Blind Repeat Treatment and follow-up (Key Secondary
Efficacy Endpoint Number 2: Response type – durable): Proportion that
responded to the composite FDA Endpoint of relief in both IBS-related
Abdominal Pain AND Stool Consistency during the PEP in the first
repeat double-blind, placebo controlled treatment phase AND continued
to respond without recurrence through the end of Week 12, independent
of any additional treatment. The results indicate a significantly
greater proportion of rifaximin-treated subjects met this endpoint as
compared to placebo-treated subjects (p-value=0.0419)
Overall, the data demonstrate that efficacy is maintained following
repeat treatment with rifaximin for up to 3 treatment cycles in subjects
with IBS-D, with no evidence of significant effects on pathogen
emergence, pathogen susceptibility or the general microbial population
in stool or skin swab samples.
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®, RUCONEST®,
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: uncertainties as to the ability to
successfully complete the proposed 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 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