Allergan to Present Data from its Anti-Infectives Portfolio at ASM Microbe 2017 in New Orleans

DUBLIN, May 31, 2017 /PRNewswire/ -- Allergan plc (NYSE: AGN) today announced new data from its anti-fectives portfolio will be featured in 16 presentations at the upcoming American Society for Microbiology (ASM) Microbe, June 1-5, 2017, in New Orleans.

Eight of the presentations will feature information about AVYCAZ^® (ceftazidime and avibactam), including data exploring the activity of AVYCAZ in resistant Gram-negative bacteria as well as results from the International Network for Optimal Resistance Monitoring (INFORM) program, one of the largest ongoing pathogen surveillance programs in the United States.

Six presentations will focus on the in vitro activity of TEFLARO^® (ceftaroline fosamil) against a variety of Gram-positive pathogens, including Methicillin-resistant Staphylococcus aureus (MRSA), with remaining presentations to focus on MONUROL^® (fosfomycin tromethamine) and ATM-AVI (an investigational, fixed-dose antibiotic combining aztreonam and avibactam), respectively.

"Allergan is at the forefront in the fight against resistant pathogens and difficult-to-treat-infections, and we remain focused on pathogen surveillance and antibiotic susceptibility research," said David Nicholson, Ph.D., Chief Research & Development Officer, Allergan. "Producing critical data that characterizes regional resistance patterns and disease prevalence helps inform the treatment decisions of physicians, and ultimately, the care of patients."

The scheduled times and titles of the presentations are as follows:

AVYCAZ (ceftazidime and avibactam)

Friday, June 2, 12:45 p.m. – 2:45 p.m. CT (Central Time)

• Activity of ceftazidime-avibactam (CAZ-AVI) against Enterobacteriaceae isolated from different infection types as part of the INFORM global surveillance program, 2015
• Activity of ceftazidime-avibactam (CAZ-AVI) against Pseudomonas aeruginosa isolated from different infection types as part of the INFORM global surveillance program, 2015
• A locally tested surveillance study to evaluate the current activity of ceftazidime-avibactam (C/A) against Gram-negative pathogens collected in the United States in 2015–2016 as part of the INFORM study
• Activity of ceftazidime-avibactam and comparator agents tested against isolates harboring β-lactamase genes detected using whole genome sequencing analysis

Saturday, June 3, 12:15 p.m. – 2:15 p.m. CT (Central Time)

• Synergistic activity of ceftazidime-avibactam (CAZ-AVI) and fosfomycin (FOS) against extended-spectrum-β-lactamase-(ESBL) and carbapenemase-producing Gram-negative (GN) bacteria
• Colistin-resistant Enterobacteriaceae in the US: Not all is lost

Sunday, June 4, 12:15 p.m. – 2:15 p.m. CT (Central Time)

• The impact of acute kidney injury (AKI) on the risk of mortality and healthcare utilization among patients treated with polymyxins for severe Gram-negative infections
• Intrinsic resistance mechanisms detected among ceftazidime-avibactam susceptible and resistant Pseudomonas aeruginosa (PSA) isolates collected from United States (US) hospitals (2015)

TEFLARO (ceftaroline fosamil)

Friday, June 2, 12:45 p.m. – 2:45 p.m. CT (Central Time)

• Ceftaroline fosamil for the treatment of pneumonia caused by methicillin-resistant Staphylococcus aureus: CAPTURE study experience
• Ceftaroline fosamil use for skin infections or community-acquired pneumonia with bacteremia

Sunday, June 4, 12:15 p.m. – 2:15 p.m. CT (Central Time)

• 2014–2015 global assessment of the in vitro activities of ceftaroline and comparative agents against bacterial pathogens frequently causing community-acquired respiratory tract infections
• Comparative in vitro activities of ceftaroline and ceftriaxone against clinical isolates of Staphylococcus aureus and coagulase-negative Staphylococci from 37 countries during 2014–2015
• Antimicrobial susceptibility trends among Staphylococcus aureus from US hospitals: results from 7 years of the ceftaroline (AWARE) surveillance program (2009-2015)
• Ceftaroline activity against Gram-positive isolates from elderly patients hospitalized with pneumonia in the intensive care unit (ICU): results from the AWARE surveillance program, 2008–2015

Monurol (fosfomycin tromethamine)

Saturday, June 3, 12:15 p.m. – 2:15 p.m. CT (Central Time)

• A Locally Tested Surveillance Study to Evaluate the Current Activity of Fosfomycin (FOS) against Enterobacteriaceae Associated with Urinary Tract Infections Collected in the United States in 2015- 2016

ATM-AVI (aztreonam and avibactam)

Friday, June 2, 12:45 p.m. – 2:45 p.m. CT (Central Time)

• In vitro activity of aztreonam-avibactam (ATM-AVI) against drug-resistant and metallo-β-lactamase-producing Enterobacteriaceae isolated as part of a global surveillance program, 2012–2015

Full abstracts can be found on the ASM Microbe website at https://www.asm.org/index.php/asm-microbe-2017.

About AVYCAZ^®
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 pathogens, including certain Enterobacteriaceae and Pseudomonas aeruginosa. In June 2016, the FDA approved the addition of Phase 3 clinical data to the label supporting the use of AVYCAZ, in combination with metronidazole, in cIAI patients, including subsets of patients with infections caused by CAZ-NS pathogens and pathogens producing certain ESBLs. In January 2017, the FDA approved the addition of Phase 3 clinical data (two studies) to the label supporting the use of AVYCAZ in patients with cUTI, including pyelonephritis, including subsets of patients with infections caused by CAZ-NS pathogens.. In one of these studies, AVYCAZ demonstrated higher combined clinical and microbiological cure rates vs. Best Available Therapy (BAT) in patients with cUTI due to CAZ-NS pathogens; similar results were seen in a subset of patients with infections caused by pathogens producing certain ESBL groups, including select KPC (Klebsiella pneumoniae carbapenemase), and AmpC beta-lactamases.

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.

Ceftazidime and avibactam is being jointly developed with Pfizer. Allergan holds the rights to commercialize ceftazidime and avibactam in North America under the brand name AVYCAZ, while Pfizer 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 Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii complex, Proteus mirabilis, and Pseudomonas aeruginosa in patients 18 years or older.

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. The decreased clinical response was not observed for patients with moderate renal impairment at baseline (CrCl of 30 to less than or equal to 50 mL/min) in the Phase 3 cUTI trials. 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 (NCSE), 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 patients (≥5% when used with metronidazole) were diarrhea (8%), nausea (7%), and vomiting (5%). The most common adverse reactions in cUTI patients (3%) were diarrhea and nausea.

Please see full Prescribing Information for AVYCAZ at www.avycaz.com.

ABOUT TEFLARO^®

TEFLARO was first approved by the U.S. FDA in October 2010 for the treatment of adults with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) due to designated susceptible pathogens. TEFLARO is a bactericidal cephalosporin with activity against both Gram-positive and Gram-negative pathogens. TEFLARO is indicated in adult and pediatric patients 2 months of age and older for the treatment of CABP, including cases caused by Streptococcus pneumoniae, and ABSSSI, including cases caused by methicillin-resistant Staphylococcus aureus (MRSA). TEFLARO is the first and only cephalosporin with activity against MRSA in ABSSSI that is approved in the U.S.. In clinical trials, TEFLARO was generally well-tolerated with an adverse event profile consistent with the cephalosporin class of antibiotics. TEFLARO has been administered in over 2.3 million days of therapy, treating more than 350,000 patients.

Allergan plc (formerly Forest Laboratories) obtained the worldwide rights (excluding Japan, where Takeda Pharmaceuticals holds rights) to TEFLARO in 2007 when it acquired Cerexa, Inc., a privately held biopharmaceutical company. In August 2009, Forest Laboratories and AstraZeneca (NYSE: AZN) entered into a definitive collaboration agreement to co-develop and commercialize ceftaroline fosamil in all markets outside the U.S., Canada and Japan.

INDICATIONS AND USAGE

• TEFLARO^® (ceftaroline fosamil) is indicated in adult and pediatric patients 2 months of age and older for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive and Gram-negative microorganisms: Staphylococcus aureus (including methicillin-susceptible and -resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca.
• TEFLARO is also indicated in adult and pediatric patients 2 months of age and older for the treatment of community-acquired bacterial pneumonia (CABP) caused by susceptible isolates of the following Gram-positive and Gram-negative microorganisms: Streptococcus pneumoniae (including cases with concurrent bacteremia), Staphylococcus aureus (methicillin-susceptible isolates only), Haemophilus influenzae, Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli.
• To reduce the development of drug-resistant bacteria and maintain the effectiveness of TEFLARO and other antibacterial drugs, TEFLARO should be used to treat only ABSSSI or CABP that are proven or strongly suspected to be caused by susceptible bacteria. Appropriate specimens for microbiological examination should be obtained in order to isolate and identify the causative pathogens and to determine their susceptibility to ceftaroline. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
  

IMPORTANT SAFETY INFORMATION 

Contraindications

• TEFLARO is contraindicated in patients with known serious hypersensitivity to ceftaroline or other members of the cephalosporin class. Anaphylaxis has been reported with ceftaroline.

Warnings and Precautions

Hypersensitivity Reactions

• Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported with beta-lactam antibacterial drugs. Before therapy with TEFLARO is instituted, careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or carbapenems should be made. Maintain clinical supervision if this product is to be given to a penicillin- or other beta-lactam-allergic patient, because cross sensitivity among beta-lactam antibacterial agents has been clearly established.
• If an allergic reaction to TEFLARO occurs, discontinue TEFLARO and institute appropriate treatment and supportive measures.

Clostridium difficile-Associated Diarrhea

• Clostridium difficile-Associated Diarrhea (CDAD) has been reported for nearly all systemic antibacterial agents, including TEFLARO, 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 agents. If CDAD is suspected or confirmed, antibacterials not directed against C. difficile should be discontinued, if possible.

Direct Coombs' Test Seroconversion

• In adults, seroconversion from a negative to a positive direct Coombs' test result occurred in 120/1114 (10.8%) of patients receiving TEFLARO and 49/1116 (4.4%) of patients receiving comparator drugs in the four pooled adult Phase 3 trials.
• In children, seroconversion from a negative to a positive direct Coombs' test result occurred in 42/234 (17.9%) of patients receiving TEFLARO and 3/93 (3.2%) of patients receiving comparator drugs in the three pooled pediatric trials.
• No adverse reactions representing hemolytic anemia were reported in any treatment group. If anemia develops during or after treatment with TEFLARO, drug-induced hemolytic anemia should be considered. If drug-induced hemolytic anemia is suspected, discontinuation of TEFLARO should be considered and supportive care should be administered to the patient if clinically indicated.

Development of Drug-Resistant Bacteria

• Prescribing TEFLARO 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 in Adults

• In the four pooled adult Phase 3 clinical trials, serious adverse reactions occurred in 98/1300 (7.5%) of patients receiving TEFLARO and 100/1297 (7.7%) of patients receiving comparator drugs. Treatment discontinuation due to adverse reactions occurred in 35/1300 (2.7%) of patients receiving TEFLARO and 48/1297 (3.7%) of patients receiving comparator drugs with the most common adverse reactions leading to discontinuation being hypersensitivity for both treatment groups at a rate of 0.3% in the TEFLARO group and 0.5% in the comparator group.
• The most common adverse reactions occurring in >2% of patients receiving TEFLARO in the adult pooled Phase 3 clinical trials were diarrhea (5%) nausea (4%), and rash (3%).

Adverse Reactions in Pediatrics

• In the three pooled pediatric clinical trials, serious adverse reactions occurred in 10/257 (4%) of patients receiving TEFLARO and 3/102 (3%) of patients receiving comparator drugs. Treatment discontinuation due to adverse reactions occurred in 10/257 (3.9%) of patients receiving TEFLARO and 2/102 (2%) of patients receiving comparator drugs with the most common adverse reaction leading to discontinuation being rash in 2/257 (0.8%) of patients treated with TEFLARO.
• The most common adverse reactions occurring in ≥ 3% of patients receiving TEFLARO in the pooled pediatric clinical trials were diarrhea (8%), rash (7%), vomiting (5%), pyrexia (3%) and nausea (3%).

Drug Interactions

• No clinical drug-drug interaction studies have been conducted with TEFLARO. There is minimal potential for drug- drug interactions between TEFLARO and CYP450substrates, inhibitors, or inducers; drugs known to undergo active renal secretion; and drugs that may alter renal blood flow.

Use in Specific Populations

• There have been no adequate and well-controlled studies with TEFLARO in pregnant or nursing women.
• Safety and effectiveness in pediatric patients below the age of 2 months have not been established as no data are available.
• Because elderly patients, those ≥65 years of age, are more likely to have decreased renal function and ceftaroline is excreted primarily by the kidney, care should be taken in dose selection in this age group and it may be useful to monitor renal function. Dosage adjustment for elderly patients should therefore be based on renal function.
• Dosage adjustment is required in adult patients with moderate (CrCl >30 to ≤50 mL/min) or severe (CrCl ≥15 to ≤30mL/min) renal impairment and in patients with end-stage renal disease (CrCl <15 mL/min).  There is insufficient information to recommend a dosage regimen for pediatric patients with CrCl < 50 ml/min/1.73m².
• The pharmacokinetics of ceftaroline in patients with hepatic impairment have not been established.

Please also see the full Prescribing Information at www.TEFLARO.com.

ABOUT MONUROL

MONUROL (fosfomycin tromethamine) was first approved by the U.S. FDA in 1997 for the treatment of women with uncomplicated urinary tract infections (uUTI) due to designated susceptible pathogens. MONUROL is a broad spectrum antibiotic and is the only one day, single dose treatment for uUTI's in women. With 18 years of experience it has a well studied clinical efficacy and safety profile. MONUROL is recommended by the Infectious Disease Society of America (IDSA) as a treatment option for uUTI and maintains good in-vitro activity against itsindicated pathogens.

Allergan plc holds the commercial rights to MONUROL in the U.S., and Zambon maintains the rights in the rest of the world.

INDICATIONS AND USAGE  FOR MONUROL

• MONUROL (fosfomycin tromethamine) is indicated only for the treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of Escherichia coli and Enterococcus faecalis.
• MONUROL is not indicated for the treatment of pyelonephritis or perinephric abscess. If persistence or reappearance of bacteriuria occurs after treatment with MONUROL, other therapeutic agents should be selected.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

• MONUROL is contraindicated in patients with known hypersensitivity to the drug.

WARNINGS

• Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including MONUROL, and may range in severity from mild diarrhea to fatal colitis. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued.

PRECAUTIONS

• Do not use more than one single dose of MONUROL to treat a single episode of acute cystitis. Repeated daily doses of MONUROL did not improve the clinical success or microbiological eradication rates compared to single dose therapy, but did increase the incidence of adverse events. Patients should be informed that if their symptoms do not improve in 2 to 3 days, they should contact their healthcare provider.
• When coadministered with MONUROL, metoclopramide lowers the serum concentration and urinary excretion of fosfomycin. Other drugs that increase gastrointestinal motility may produce similar effects.
• There are no adequate and well-controlled studies of MONUROL in pregnant women. Therefore, MONUROL should be used in pregnancy only if clearly needed.
• It is not known whether fosfomycin tromethamine is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from MONUROL, a decision should be made whether to discontinue nursing or to not administer the drug, taking into account the importance of the drug to the mother.
• Safety and effectiveness in children age 12 years and under have not been established in adequate and well-controlled studies.

ADVERSE REACTIONS

• In clinical trials, the most frequently reported adverse events occurring in >1% of the MONUROL-treated patients (n=1233) were: diarrhea (9.0%), vaginitis (5.5%), nausea (4.1%), headache (3.9%), dizziness (1.3%), asthenia (1.1%), and dyspepsia (1.1%).

Please also see the full Prescribing Information at www.MONUROL.com

About Allergan plc
Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a bold, global pharmaceutical company and a leader in a new industry model – Growth Pharma. Allergan is focused on developing, manufacturing and commercializing branded pharmaceutical, device, biologic, surgical and regenerative medicine 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, a model of research and development, which defines our approach to identifying and developing game-changing ideas and innovation for better patient care. With this approach, Allergan has built one of the broadest development pipelines in the pharmaceutical industry with 70+ mid-to-late stage pipeline programs currently in development.

Allergan's success is powered by our more than 18,000 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 every day.

For more information, visit Allergan's website at www.Allergan.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 on existing trends and information as of the date of this release. 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, 2016 and Allergan's Quarterly Report on Form 10-Q for the period ended March 31, 2017. Except as expressly required by law, Allergan disclaims any intent or obligation to update these forward-looking statements.

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