Allergan Announces FDA Approval of Updated Label for TEFLARO(R) (ceftaroline fosamil)

- Label now includes new data on patients with ABSSSI with baseline Staphylococcus aureus bacteremia and supports shorter intravenous (IV) infusion time for TEFLARO -
DUBLIN, Sept. 2, 2015 /PRNewswire/ -- Allergan plc (NYSE: AGN) 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 TEFLARO® (ceftaroline fosamil) for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). The approved label contains new clinical data from two ABSSSI trials that included patients with baseline Staphylococcus aureus bacteremia. Bacteremia is the presence of bacteria in the bloodstream.  Bacteremia complicates infection treatment and in the most serious cases, can be fatal.

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With this updated label, TEFLARO also is now approved to be administered by intravenous (IV) infusion in five minutes to one hour in adult patients 18 years and older.

"The new clinical data in the TEFLARO label will allow for use in ABSSSI patients with baseline S. aureus bacteremia, the incidence of which has increased sharply in recent years, and provides physicians with the ability to treat patients with these serious infections," said David Nicholson, Executive Vice President & President, Global Brands Research and Development, Allergan. "In addition, with a shorter infusion time TEFLARO provides increased flexibility in dosing that may allow physicians, nurses and other healthcare professionals to optimize the delivery of care in hospital and home settings."

Updated ABSSSI Trial Data

The sNDA approval was based on a subset of data coming from two identical pivotal trials (CANVAS 1 and 2) comparing ABSSSI patients treated with TEFLARO monotherapy to patients treated with vancomycin plus aztreonam. Of the 693 patients in the modified intent-to-treat (MITT) population in the TEFLARO arm in the two ABSSSI trials, 20 patients had baseline Staphylococcus aureus bacteremia (nine cases of methicillin-resistant Staphylococcus aureus [MRSA] and 11 cases of methicillin-susceptible Staphylococcus aureus [MSSA]). Thirteen of these 20 patients (65%) achieved clinical response with TEFLARO at Day 3 and 18 of 20 patients (90%) were considered clinical success at Test of Cure. This data is now included in the clinical trial section of the Teflaro prescribing information.

Updated Dosing Time

TEFLARO can now be administered in 5 minutes to one hour in the treatment of patients with ABSSSI and CABP due to designated susceptible pathogens. Recommended dosing for TEFLARO is 600 mg IV for 5 to 60 minutes by IV every 12 hours for 5 to 14 days for ABSSSI and 5 to 7 days for CABP.

Patients with renal impairment should receive TEFLARO in a 5 to 60 minute IV infusion every 12 hours at the following dosages:

>50 CrCl (mL/min): 600 mg 
>30 to <50 CrCl (mL/min): 400 mg
>15 to <30 CrCl (mL/min): 300 mg
End-stage renal disease (CrCl < 15 mL/min), including hemodialysis: 200 mg

ABOUT TEFLARO® (ceftaroline fosamil)
TEFLARO was first approved by the U.S. FDA in October 2010 for the treatment of adults with CABP and ABSSSI due to designated susceptible pathogens.  TEFLARO is a bactericidal cephalosporin with activity against both Gram-positive and Gram-negative pathogens. TEFLARO is indicated 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 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.

Forest 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 is indicated for the treatment of acute ABSSSI caused by susceptible bacterial isolates of the following Gram-positive and Gram-negative microorganisms: Staphylococcus aureus (methicillin-susceptible and -resistant isolates) Streptococcus pyogenes, Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae and Klebsiella oxytoca.

TEFLARO is also indicated for the treatment of CABP caused by susceptible bacterial 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 and anaphylactoid reactions have 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

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 Phase 3 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 the four pooled 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.
No adverse reactions occurred in greater than 5% of patients receiving TEFLARO. The most common adverse reactions occurring in >2% of patients receiving TEFLARO in the pooled Phase 3 clinical trials were diarrhea, nausea, and rash.
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

TEFLARO has not been studied in pregnant women. Therefore, TEFLARO should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.
It is not known whether ceftaroline is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when TEFLARO is administered to a nursing woman.
Safety and effectiveness in pediatric patients have not been established.
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 patients with moderate (CrCl >30 to =50 mL/min) or severe (CrCl =15 to =30 mL/min) renal impairment and in patients with end-stage renal disease (CrCl <15 mL/min).
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 ABSSSI
There were more than 4.8 million hospital admissions of adults with ABSSSI from 2005 through 2011, which included patients with cellulitis, erysipelas, wound infection and major cutaneous abscess. In fact, hospital admissions for ABSSSI significantly increased by 17.3 percent during this timeframe. The majority of all skin and soft tissue infections in hospitalized patients are caused by streptococci and Staphylococcus aureus, and approximately 59 percent of these Staphylococcus aureus infections in the U.S. are estimated to be caused by MRSA. Early and effective treatment of ABSSSI is critical to optimize patient recovery and for certain patients may also help to avoid potentially lengthy and costly hospital stays.

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, 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.

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 Quarterly Report on Form 10-Q for the quarter ended March 31, 2015 (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

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SOURCE Allergan plc

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