DUBLIN, June 23, 2016 /PRNewswire/ -- Allergan plc
(NYSE: AGN), a leading global pharmaceutical company, today
announced the U.S. Food and Drug Administration (FDA) has approved
the company's supplemental New Drug Application (sNDA) to update
the label for AVYCAZ® (ceftazidime and avibactam) with
clinical data from a Phase 3 trial evaluating the safety and
efficacy of AVYCAZ, in combination with metronidazole, for the
treatment of complicated intra-abdominal infections (cIAI) caused
by designated susceptible microorganisms. The approved label also
contains data from a subset of patients in this trial with
infections due to ceftazidime-nonsusceptible (CAZ-NS) pathogens, as
well as a subset who had pathogens producing certain
extended-spectrum beta-lactamases (ESBLs).
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"Complicated intra-abdominal infections represent a major
therapeutic challenge for physicians," said David Nicholson, Ph.D., Chief R&D Officer,
Allergan. "AVYCAZ has been used in thousands of patients with these
difficult-to-treat infections since it was first approved by the
FDA in February 2015. The addition of
these data to the label provides physicians with consistent
evidence of the activity of AVYCAZ against some of the most
challenging pathogens, including those for which we currently have
limited treatment options."
"As a leader in anti-infectives, Allergan is committed to
furthering the science needed to address the growing prevalence of
these difficult-to-treat infections, helping physicians better
understand the threat of challenging pathogens and equipping them
with much needed treatments for their patients," Nicholson
said.
This sNDA approval is based on results from a Phase 3 study that
evaluated the efficacy and safety of AVYCAZ, in combination
with metronidazole, for the treatment of patients with cIAI. The
study showed that clinical cure rates at the Test of Cure (TOC)
time point met the primary endpoint of statistical non-inferiority
to meropenem. In a subset of patients with infections due to
ceftazidime-resistant pathogens, as well as a subset who had
pathogens that produced certain ESBLs, clinical cure rates for
patients treated with AVYCAZ were similar to the overall
results.
AVYCAZ has demonstrated in vitro activity against
Enterobacteriaceae in the presence of some beta-lactamases and
ESBLs of the following groups: TEM, SHV, CTX-M, Klebsiella
pneumoniae carbapenemase (KPCs), AmpC and certain oxacillinases
(OXA). AVYCAZ also demonstrated in vitro activity
against Pseudomonas aeruginosa in the presence of
some AmpC beta-lactamases, and certain strains lacking outer
membrane porin (OprD). AVYCAZ is not active against bacteria that
produce metallo-beta lactamases and may not have activity against
Gram-negative bacteria that over-express efflux pumps or have porin
mutations.
AVYCAZ was first approved in the U.S. in February 2015 for the treatment of adult patients
with cIAI, in combination with metronidazole, and complicated
urinary tract infections (cUTI), including pyelonephritis, caused
by susceptible bacteria, including certain Enterobacteriaceae and
Pseudomonas aeruginosa. In the treatment of cUTI, as only
limited clinical safety and efficacy data for AVYCAZ are currently
available, reserve AVYCAZ for use in patients with cUTI who have
limited or no alternative treatment options. Phase 3 studies
evaluating the safety and efficacy of AVYCAZ for the treatment of
cUTI have been completed, and the data is being analyzed for
submission later this year.
About AVYCAZ®
AVYCAZ is an antibiotic
developed to treat certain serious Gram-negative bacterial
infections. It consists of ceftazidime, a third-generation
cephalosporin and an established and respected treatment for
serious Gram-negative bacterial infections, and avibactam, a non-β
lactam β-lactamase inhibitor.
The addition of avibactam to ceftazidime protects ceftazidime
from breakdown by certain β-lactamases. AVYCAZ offers a
differentiated profile in the treatment of cIAI (in combination
with metronidazole) and cUTI caused by designated microorganisms
through its in vitro activity against Enterobacteriaceae,
including those that produce certain ESBLs and KPCs, and
difficult-to-treat Pseudomonas aeruginosa.
Ceftazidime and avibactam is being jointly developed with
AstraZeneca. Allergan holds the rights to commercialize ceftazidime
and avibactam in North America,
while AstraZeneca holds the rights to commercialize the combination
in the rest of the world.
INDICATIONS AND USAGE
Complicated Intra-Abdominal Infections (cIAI)
AVYCAZ® (ceftazidime and avibactam), in combination with
metronidazole, is indicated for the treatment of complicated
intra-abdominal infections (cIAI) caused by the following
susceptible Gram-negative microorganisms: Escherichia coli,
Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae,
Klebsiella oxytoca, Citrobacter freundii complex, and
Pseudomonas aeruginosa in patients 18 years or older.
Complicated Urinary Tract Infections (cUTI), including
Pyelonephritis
AVYCAZ is indicated for the treatment of
complicated urinary tract infections (cUTI) including
pyelonephritis caused by the following susceptible microorganisms:
Escherichia coli, Klebsiella pneumoniae, Citrobacter
koseri, Enterobacter aerogenes, Enterobacter
cloacae, Citrobacter freundii, Proteus
spp., and Pseudomonas aeruginosa in patients 18 years
or older.
In the treatment of cUTI, as only limited clinical safety and
efficacy data for AVYCAZ are currently available, reserve AVYCAZ
for use in patients with cUTI who have limited or no alternative
treatment options.
Usage
To reduce the development of drug-resistant
bacteria and maintain the effectiveness of AVYCAZ and other
antibacterial drugs, AVYCAZ should be used to treat only indicated
infections that are proven or strongly suspected to be caused by
susceptible bacteria.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
AVYCAZ is contraindicated in
patients with known serious hypersensitivity to the components of
AVYCAZ (ceftazidime and avibactam), avibactam‑containing products,
or other members of the cephalosporin class.
WARNINGS AND PRECAUTIONS
- In a Phase 3 cIAI trial, clinical cure rates were lower in a
subgroup of patients with baseline creatinine clearance (CrCl) of
30 to less than or equal to 50 mL/min compared to those with CrCl
greater than 50 mL/min. The reduction in clinical cure rates was
more marked in patients treated with AVYCAZ plus metronidazole
compared to meropenem-treated patients. Clinical cure rates in
patients with normal renal function/mild renal impairment (CrCl
greater than 50 mL/min) was 85% (322/379) with AVYCAZ plus
metronidazole vs 86% (321/373) with meropenem, and clinical cure
rates in patients with moderate renal impairment (CrCl 30 to less
than or equal to 50 mL/min) was 45% (14/31) with AVYCAZ plus
metronidazole vs 74% (26/35) with meropenem. Within this subgroup,
patients treated with AVYCAZ received a 33% lower daily dose than
is currently recommended for patients with CrCl of 30 to less than
or equal to 50 mL/min. Monitor CrCl at least daily in patients with
changing renal function and adjust the dosage of AVYCAZ
accordingly.
- Serious and occasionally fatal hypersensitivity (anaphylactic)
reactions and serious skin reactions have been reported in patients
receiving beta-lactam antibacterial drugs. Before therapy with
AVYCAZ is instituted, careful inquiry about previous
hypersensitivity reactions to other cephalosporins, penicillins, or
carbapenems should be made. Exercise caution if this product
is to be given to a penicillin or other beta-lactam-allergic
patient because cross sensitivity among beta-lactam antibacterial
drugs has been established. Discontinue the drug if an allergic
reaction to AVYCAZ occurs.
- Clostridium difficile-associated diarrhea (CDAD) has
been reported for nearly all systemic antibacterial drugs,
including AVYCAZ, and may range in severity from mild diarrhea to
fatal colitis. Careful medical history is necessary because CDAD
has been reported to occur more than 2 months after the
administration of antibacterial drugs. If CDAD is suspected or
confirmed, antibacterials not directed against C.
difficile should be discontinued, if possible.
- Seizures, nonconvulsive status epilepticus, encephalopathy,
coma, asterixis, neuromuscular excitability, and myoclonia have
been reported in patients treated with ceftazidime, particularly in
the setting of renal impairment. Adjust dosing based on creatinine
clearance.
- Prescribing AVYCAZ in the absence of a proven or strongly
suspected bacterial infection is unlikely to provide benefit to the
patient and increases the risk of the development of drug-resistant
bacteria.
ADVERSE REACTIONS
- The most common adverse reactions in cIAI (incidence of ≥5%
when used with metronidazole) were diarrhea (8%), nausea (7%), and
vomiting (5%). In cUTI, the most common adverse reactions
(incidence of ≥10%) were constipation (10%) and anxiety (10%).
Please see full Prescribing Information for AVYCAZ at
www.avycaz.com.
About Gram-Negative Infections
Gram-negative bacteria
are highly adaptive pathogens that can develop resistance through
several mechanisms and can pass along genetic materials that allow
other bacteria to become drug-resistant as well. Gram-negative
bacteria are common causes of complicated intra-abdominal
infections and urinary tract infections.
Complicated intra-abdominal infections are a considerable
problem. The most common pathogens associated with complicated
intra-abdominal infections include Escherichia coli, Klebsiella
pneumoniae, Proteus mirabilis, Providencia stuartii, Enterobacter
cloacae, Klebsiella oxytoca and Pseudomonas aeruginosa.
Complicated urinary tract infections are also often caused by
Gram-negative pathogens. Escherichia coli (E. coli) is
one of the common organisms causing complicated urinary tract
infections (UTIs), and is becoming increasingly resistant to
available antibiotics.
According to the Centers for Disease Control and
Prevention (CDC), rates of Klebsiella
pneumoniae carbapenemase (KPC) producing organisms in
particular have increased across the country significantly in the
past 10 years. In addition, E.
coli, Klebsiella (K.
pneumoniae and K. oxytoca) and
Pseudomonas aeruginosa are on the rise.
About Allergan
Allergan plc (NYSE: AGN),
headquartered in Dublin, Ireland,
is a unique, global pharmaceutical company and a leader in a new
industry model—Growth Pharma. Allergan is focused on
developing, manufacturing, and commercializing innovative branded
pharmaceuticals, high-quality generic and over-the-counter
medicines, and biologic products for patients around the world.
Allergan markets a portfolio of best-in-class products that
provide valuable treatments for the central nervous system, eye
care, medical aesthetics, gastroenterology, women's health,
urology, cardiovascular and anti-infective therapeutic categories,
and operates the world's third-largest global generics business,
providing patients around the globe with increased access to
affordable, high-quality medicines. Allergan is an industry leader
in research and development, with one of the broadest development
pipelines in the pharmaceutical industry and a leading position in
the submission of generic product applications globally.
With commercial operations in approximately 100 countries,
Allergan is committed to working with physicians, health care
providers, and patients to deliver innovative and meaningful
treatments that help people around the world live longer, healthier
lives.
For more information, visit Allergan's website at
www.allergan.com.
About AstraZeneca
AstraZeneca is a global,
innovation-driven biopharmaceutical business that focuses on the
discovery, development and commercialization of prescription
medicines, primarily for the treatment of cardiovascular,
metabolic, respiratory, inflammation, autoimmune, oncology,
infection and neuroscience diseases. AstraZeneca operates in over
100 countries and its innovative medicines are used by millions of
patients worldwide. For more information please visit:
www.astrazeneca.com
Forward-Looking Statement
Statements contained in
this press release that refer to future events or other
non-historical facts are forward-looking statements that reflect
Allergan's current perspective of existing trends and information
as of the date of this release. Except as expressly required by
law, Allergan disclaims any intent or obligation to update these
forward-looking statements. Actual results may differ materially
from Allergan's current expectations depending upon a number of
factors affecting Allergan's business. These factors include, among
others, the difficulty of predicting the timing or outcome of FDA
approvals or actions, if any; the impact of competitive products
and pricing; market acceptance of and continued demand for
Allergan's products; difficulties or delays in manufacturing; and
other risks and uncertainties detailed in Allergan's periodic
public filings with the Securities and Exchange Commission,
including but not limited to Allergan's Annual Report on Form 10-K
for the year ended March 31, 2016
(certain of such periodic public filings having been filed under
the "Actavis plc" name). Except as expressly required by law,
Allergan disclaims any intent or obligation to update these
forward-looking statements.
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SOURCE Allergan plc