Allergan To Present New Data From Its Anti-Infectives Portfolio At IDWeek 2017 In San Diego

Presentations will feature microbiology, clinical and health outcomes and economics data, including an oral presentation on the effects of carbapenem-resistant Enterobacteriacae (CRE) and delayed appropriate therapy on clinical outcomes in patients with serious infections due to Enterobacteriaceae.

The Company will also present investigational data from the Phase 3 REPROVE clinical trial of AVYCAZ® (ceftazidime and avibactam) in patients with Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP). Additionally, the Company will present findings from the CAPTURE Study evaluating the use of TEFLARO® (ceftaroline fosamil) in the treatment of intensive care unit patients with pneumonia.

Additional presentations provide data on the use of DALVANCE® (dalbavancin) for the treatment of Acute Bacterial Skin and Skin Struction Infection (ABSSSI) in patients with various comorbidities including obesity, diabetes and Systemic Inflammatory Response Syndrome (SIRS). Other presentations will focus on the treatment of ABSSSI related to healthcare provider treatment decisions in emergency departments and related to patient reported preferences.

“Our innovation and open science model has put Allergan, along with a handful of other companies, at the forefront in the fight against infectious diseases,” said David Nicholson, Ph.D., Chief Research and Development Officer, Allergan. “Our presentations at IDWeek 2017 cover a broad range of therapeutic areas and we are pleased to share these results with the Infectious Disease community and continue to work with them to realize the full potential of our treatments.”

Details of selected presentations are below. The complete program of titles and abstracts can be accessed on the IDWeek 2017 website at www.idweek.org.

Oral Presentation

Thursday, October 5, 11:45 a.m. – 12:00 p.m. PST

Presentation 141: Carbapenem-resistant Enterobacteriaceae (CRE) or Delayed Appropriate Therapy (DAT) – Does One Effect Outcomes More than the Other among Patients with Serious Infections due to Enterobacteriaceae?

Poster Presentations

AVYCAZ (ceftazidime and avibactam)

Friday, October 6, 12:30 p.m. – 2:00 p.m. PST

Poster 1201: Comparative in vitro Activities of Ceftazidime-avibactam and Ceftolozane-tazobactam against Characterized β-Lactamase-producing Pseudomonas aeruginosa
Poster 1237: Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Tested against Enterobacteriaceae and Pseudomonas aeruginosa from United States (US) Medical Centers Stratified by Infection Type (2015-2016)

Saturday, October 7, 12:30 p.m. – 2:00 p.m. PST

Poster 1864: Phase 3, randomized, double-blind noninferiority (NI) study of ceftazidime-avibactam (CAZ-AVI) versus meropenem (MER) in the treatment of patients with Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP): Analyses of the REPROVE study per US FDA Endpoints

DALVANCE (dalbavancin)

Thursday, October 5, 12:30 p.m. – 2:00 p.m. PST

Poster 210: Efficacy and Safety of Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infection (ABSSSI) in Patients with Diabetes Mellitus
Poster 256: Efficacy and Safety of Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in the Obese Population

Saturday, October 7, 12:30 p.m. – 2:00 p.m. PST

Poster 1876: Treatment of Acute Bacterial Skin and Skin Structure Infection (ABSSSI) with Dalbavancin in Patients with Systemic Inflammatory Response Syndrome (SIRS)

TEFLARO (ceftaroline fosamil)

Saturday, October 7, 12:30 p.m. – 2:00 p.m. PST

Poster 1993: Ceftaroline Fosamil for the Treatment of Intensive Care Unit Patients with Pneumonia: CAPTURE Study Experience
Poster 1884: Ceftaroline Fosamil (CPT) versus Vancomycin (VAN) for Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

Clinical and Health Outcomes and Economics Data

Thursday, October 5, 12:30 p.m. – 2:00 p.m. PST

Poster 783: Associations between Timeliness of Therapy and Clinical and Economic Outcomes Among Patients with Serious Infections due to Gram-negative Bacteria (GNB): How Much Does Delayed Appropriate Therapy (DAT) Matter?

Saturday, October 7, 12:30 p.m. – 2:00 p.m. PST

Poster 1894: Clinical and Economic Comparison of Ceftaroline Fosamil (CPT) and Daptomycin (DAP) for Methicillin-Resistant Staphylococcus aureus (MRSA) Bloodstream Infections (BSI)

About AVYCAZ

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 also see the full Prescribing Information at www.AVYCAZ.com.

About DALVANCE

INDICATIONS AND USAGE

DALVANCE^® (dalbavancin) for injection is indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant strains), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus group (including S. anginosus, S. intermedius, S. constellatus) and Enterococcus faecalis (vancomycin-susceptible strains).

To reduce the development of drug-resistant bacteria and maintain the effectiveness of DALVANCE and other antibacterial agents, DALVANCE should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria.

IMPORTANT SAFETY INFORMATION

Contraindications

DALVANCE is contraindicated in patients with known hypersensitivity to dalbavancin.

Warnings and Precautions

Hypersensitivity Reactions

Serious hypersensitivity (anaphylactic) and skin reactions have been reported with glycopeptide antibacterial agents, including DALVANCE. Exercise caution in patients with known hypersensitivity to glycopeptides due to the possibility of cross-sensitivity. If an allergic reaction occurs, treatment with DALVANCE should be discontinued.

Infusion-related Reactions

Rapid intravenous infusion of DALVANCE can cause reactions, including flushing of the upper body, urticaria, pruritus, and rash.

Hepatic Effects

ALT elevations with DALVANCE treatment were reported in clinical trials.

Clostridium difficile-associated Diarrhea

Clostridium difficile-associated diarrhea (CDAD) has been reported with nearly all systemic antibacterial agents, including DALVANCE, with severity ranging from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs.

Development of Drug-resistant Bacteria

Prescribing DALVANCE 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 patients treated with DALVANCE were nausea (4.7%), headache (3.8%), and diarrhea (3.4%).

Use in Specific Populations

There have been no adequate and well-controlled studies with DALVANCE in pregnant or nursing women. DALVANCE should only be used if the potential benefit justifies the potential risk in these populations.
In patients with renal impairment whose known creatinine clearance is less than 30 mL/min and who are not receiving regularly scheduled hemodialysis, the recommended regimen of DALVANCE is 1125 mg, administered as a single dose, or 750 mg followed one week later by 375 mg. No dosage adjustment is recommended for patients receiving regularly scheduled hemodialysis, and DALVANCE can be administered without regard to the timing of hemodialysis.
Caution should be exercised when prescribing DALVANCE to patients with moderate or severe hepatic impairment (Child-Pugh Class B or C) as no data are available to determine the appropriate dosing in these patients.

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

About TEFLARO

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 CYP450 substrates, 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. TEFLARO should only be used if the potential benefit justifies the potential risk in these populations.
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 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 65+ 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 June 30, 2017. Except as expressly required by law, Allergan disclaims any intent or obligation to update these forward-looking statements.