DUBLIN, Oct. 11, 2016 /PRNewswire/ -- Allergan plc
(NYSE: AGN), a leading global pharmaceutical company, today
announced the U.S. Food and Drug Administration (FDA) has accepted
for filing the company's supplemental New Drug Application (sNDA)
for AVYCAZ® (ceftazidime and avibactam), seeking the
addition of new Phase 3 clinical trial data evaluating AVYCAZ in
patients with complicated urinary tract infections (cUTI),
including pyelonephritis, due to designated susceptible pathogens
to the current product label. The FDA granted priority review
status to this application based on the previous Qualified
Infectious Disease Product (QIDP) designation for AVYCAZ and is
expected to take action on the filing in the first quarter of
2017.
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"The initial AVYCAZ approval represented an important step
forward in bringing antibiotics for difficult-to-treat infections
to market, allowing us to provide physicians with earlier access to
AVYCAZ for their patients in need while continuing to explore the
full benefit of the drug," said David
Nicholson, Ph.D., Chief R&D Officer, Allergan. "These
Phase 3 data offer additional information about the efficacy of
AVYCAZ in treating complicated urinary tract infections caused by
certain Gram-negative pathogens and add to the complete body of
clinical data."
"We look forward to working with the FDA to add these data
to the AVYCAZ label and are committed to the ongoing development of
our anti-infectives portfolio to ensure physicians have both the
access and confidence to use the tools needed to address serious
infections," Nicholson said.
AVYCAZ was first approved in the U.S. in February 2015 for the treatment of adult patients
with complicated intra-abdominal infections (cIAI), in combination
with metronidazole, and cUTI, including pyelonephritis, caused by
designated susceptible bacteria, including certain
Enterobacteriaceae and Pseudomonas aeruginosa. In
June 2016, the FDA approved the
addition of data from a Phase 3 cIAI clinical trial to the label
that evaluated the safety and efficacy of AVYCAZ, in combination
with metronidazole, for the treatment of cIAI including data from a
subset of patients with infections caused by
ceftazidime-nonsusceptible (CAZ-NS) pathogens and a subset of
patients with pathogens producing certain extended-spectrum
beta-lactamases (ESBLs).
The application included results from a Phase 3 study evaluating
the efficacy and safety of AVYCAZ for the treatment of patients
with cUTI, including pyelonephritis. In this study, AVYCAZ
demonstrated non-inferiority to doripenem with regard to both
co-primary endpoints (patient-reported symptomatic response at Day
5 and the combined patient-reported symptomatic response and
microbiological eradication at the Test of Cure [TOC] visit) in the
microbiologically modified intent-to treat (mMITT) population. In a
subset of patients with cUTI due to CAZ-NS 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. The application also included data from a second
open-label Phase 3 study comparing AVYCAZ to best available therapy
for treating patients with cUTI due to CAZ-NS pathogens. The
results of this study were consistent with the pivotal Phase 3
study evaluating the efficacy and safety of AVYCAZ for the
treatment of patients with cUTI.
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 overexpress efflux pumps or have porin
mutations.
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
under the brand name AVYCAZ, while AstraZeneca holds the rights to
commercialize the combination in the rest of the world under the
brand name Zavicefta.
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 only to treat 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, Citrobacter freundii complex
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 plc
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 leading brands and best-in-class
products for the central nervous system, eye care, medical
aesthetics and dermatology, gastroenterology, women's health,
urology and anti-infective therapeutic categories.
Allergan is an industry leader in Open Science, the Company's
R&D model, which defines our approach to identifying and
developing game-changing ideas and innovation for better patient
care. This approach has led to Allergan building one of the
broadest development pipelines in the pharmaceutical industry with
65+ mid-to-late stage pipeline programs in development.
Our Company's success is powered by our more than 16,000 global
colleagues' commitment to being Bold for Life. Together, we
build bridges, power ideas, act fast and drive results for our
customers and patients around the world by always doing what is
right.
With commercial operations in approximately 100
countries, Allergan is committed to working with
physicians, healthcare 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 December 31, 2015
and Quarterly Report on Form 10-Q for the quarter ended
June 30, 2016 (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.
CONTACTS:
Investors:
Lisa
DeFrancesco
(862) 261-7152
Media:
Mark Marmur
(862) 261-7558
Fran DeSena
(973) 517-3132
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SOURCE Allergan plc