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FDA Accepts Supplemental New Drug Application (sNDA) for TEFLARO® (ceftaroline fosamil)

AZNCF | February 16, 2016

- Application Seeks to Expand Label with New Data on Pediatric Patients 2 Months of Age and Older with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) and Community-Acquired Bacterial Pneumonia (CABP) -

PR Newswire

DUBLIN, Feb. 16, 2016

DUBLIN, Feb. 16, 2016 /PRNewswire/ -- Allergan plc (NYSE: AGN) today announced the U.S. Food and Drug Administration (FDA) has accepted for filing the company's supplemental New Drug Application (sNDA) for TEFLARO^® (ceftaroline fosamil). If approved, this filing will expand the label of TEFLARO beyond adults to include the treatment of children two months of age and older with acute bacterial skin and skin structure infections (ABSSSI) including infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and community-acquired bacterial pneumonia (CABP) caused by Staphylococcus pneumoniae and other designated susceptible bacteria.

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"The impact of ABSSSI and CABP are significant among children, particularly those under the age of five who are often hospitalized due to these infections. This acceptance brings us one step closer to providing another choice for physicians to properly treat pediatric patients with ABSSSI and CABP, including those infections caused by difficult-to-treat pathogens," said David Nicholson, Executive Vice President & President, Global Brands Research and Development, Allergan. "We remain committed to the research and development of TEFLARO and our entire anti-infective portfolio to improve care and treatment of patients who have limited FDA approved options for these types of infections."

This application was based on results from five clinical studies evaluating TEFLARO in pediatric patients, including one active-controlled study in subjects with ABSSSI, two active-controlled studies in pediatric patients with CABP and two pharmacokinetic (PK) studies. In the ABSSSI active-controlled study the efficacy and safety of TEFLARO were compared with vancomycin or cefazolin with or without aztreonam. In the CABP studies, TEFLARO was compared with ceftriaxone or ceftriaxone plus vancomycin.

In the ABSSSI pediatric trial, the clinical response at Study Day 3, as measured by cessation of lesion spread and absence of fever, was 80.4 percent (86/107) in patients treated with TEFLARO and 75 percent (39/52) for the comparator group.

The CABP pediatric trials evaluated the efficacy and safety of two separate dosing regimens of TEFLARO. In the trial submitted for this pediatric filing, the clinical response at Study Day 4, as measured by improvement in at least two out of seven symptoms (cough, dyspnea, chest pain, sputum production, chills, feeling of warmth/feverish and exercise intolerance or lethargy) as well as by no worsening of these symptoms, was 69.2 percent (74/107) for patients treated with TEFLARO and 66.7 percent (24/36) in the comparator group.

ABOUT TEFLARO^®
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.

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 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

In 2014, there were 2.7 million hospital admissions for ABSSSI, of which 11 percent were for pediatric patients, which included patients with cellulitis, erysipelas, wound infection and major cutaneous abscess. 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 CABP

In 2014, there were 1.3 million hospital admissions for CABP, of which 8 percent were for pediatric patients. While the overall incidence of pneumonia is declining, it is still a leading cause of mortality accounting for more than 50,000 deaths in 2013. The cost of care for patients with CABP in the U.S. has been estimated to be more than $10 billion annually.

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 September 30, 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.