Actavis Announces FDA Acceptance of sNDA to Expand TEFLARO® (ceftaroline fosamil) Labeling

DUBLIN, Feb. 4, 2015 /PRNewswire/ -- Actavis plc (NYSE: ACT) today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing Actavis' supplemental New Drug Application (sNDA) to expand the label for TEFLARO^® (ceftaroline-fosamil) to treat cases of concurrent bacteremia in patients with acute bacterial skin and skin structure infections (ABSSSIs) caused by susceptible isolates of Staphylococcus aureus (including Methicillin-susceptible and resistant isolates).

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Concurrent bacteremia is a secondary infection that occurs when bacteria spreads from the primary site of infection to the blood stream. Concurrent bacteremia complicates infection treatment and in the most serious cases can be fatal.

"The incidence of S. aureus bacteremia and its complications has increased sharply in recent years due to the rise in frequency of invasive procedures, higher numbers of immunocompromised patients and greater resistance of S. aureus strains to available antibiotics," said David Nicholson, Senior Vice President, Global Brands Research and Development, Actavis. "We are pleased with the FDA's acceptance of this sNDA and believe a label expansion has the potential to make a meaningful difference for patients and physicians in desperate need of alternative treatment options."

The sNDA submission 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. Clinical response was evaluated at Test of Cure (TOC) and Study Day 3 in subjects who had S. aureus bacteremia at baseline in the microbiological modified intent-to-treat (mMITT) population. TEFLARO patients showed a comparable response at TOC (90%) and higher response at Study Day 3 (65%), compared to patients treated with vancomycin/aztreonam. Supportive evidence is provided by data from an investigator-conducted case control study, literature reports, microbiological surveillance, and animal model studies. 

Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target of Q3 2015 to complete its review.

About Teflaro® (ceftaroline fosamil)
Teflaro is a broad-spectrum bactericidal cephalosporin with activity against both gram-positive pathogens and gram-negative pathogens. Teflaro is indicated for the treatment of CABP, including cases caused by Streptococcus pneumoniae bacteremia, and ABSSSI, including cases caused by MRSA. In clinical trials, Teflaro was generally well-tolerated with an adverse event profile consistent with the cephalosporin class of antibiotics.

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 entered into a definitive collaboration agreement to co-develop and commercialize ceftaroline fosamil in all markets outside the U.S., Canada and Japan.

Indications
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 (including 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.

Important Safety Information

Contraindications
Known serious hypersensitivity to Teflaro or other members of the cephalosporin class. Anaphylaxis and anaphylactoid reactions have been reported with ceftaroline.

Warnings and Precautions

Hypersensitivity Reactions
Serious hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported with beta-lactam antibiotics, including ceftaroline. Exercise caution in patients with known hypersensitivity to beta-lactam antibiotics including Teflaro. Before therapy with Teflaro is instituted, careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or carbapenems should be made. If this product is to be given to penicillin or other beta-lactam-allergic patient, caution should be exercised because cross sensitivity among beta-lactam antibacterial agents has been clearly established. If an allergic reaction to Teflaro occurs, the drug should be discontinued. Serious acute hypersensitivity (anaphylactic) reactions require emergency treatment with epinephrine and other emergency measures, that may include airway management, oxygen, intravenous fluids, antihistamines, corticosteroids, and vasopressors as clinically indicated.

Clostridium difficile-Associated Diarrhea
Clostridium difficile-associated diarrhea (CDAD) has been reported for nearly all 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.

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.

Direct Coombs Test Seroconversion
In the pooled Phase 3 CABP trials, 51/520 (9.8%) of patients treated with Teflaro compared to 24/534 (4.5%) of patients treated with ceftriaxone seroconverted from a negative to a positive direct Coombs' test result. No clinical 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.

Drug Interactions
No clinical drug-drug interaction studies have been conducted with ceftaroline fosamil. In vitro studies in human liver microsomes indicated that neither ceftaroline fosamil nor ceftaroline inhibits the major cytochrome P450 isoenzymes. Therefore neither ceftaroline fosamil nor ceftaroline are expected to inhibit or induce the clearance of drugs that are metabolized by these metabolic pathways in a clinically relevant manner.

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

About ABSSSI
ABSSSI are among the most common infections treated in the hospital setting and are caused by both gram-positive and gram-negative pathogens. MRSA is the most frequent cause of ABSSSI presenting to emergency departments in the U.S. and were reported as the cause of more than 18,000 deaths in 2005.

About Actavis
Actavis plc (NYSE:ACT), headquartered in Dublin, Ireland, is a unique specialty pharmaceutical company focused on developing, manufacturing and commercializing high quality affordable generic and innovative branded pharmaceutical products for patients around the world. 

Actavis markets a broad portfolio of branded and generic pharmaceuticals and develops innovative medicines for patients suffering from diseases principally in the central nervous system, gastroenterology, women's health, urology, cardiovascular, respiratory and anti-infective therapeutic categories.  The Company is an industry leader in product research and development, with one of the broadest brand development pipelines in the pharmaceutical industry, and a leading position in the submission of generic product applications. Actavis has commercial operations in more than 60 countries and operates more than 30 manufacturing and distribution facilities around the world.

For more information, visit Actavis' website at www.actavis.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 Actavis' current perspective of existing trends and information as of the date of this release. Except as expressly required by law, Actavis disclaims any intent or obligation to update these forward-looking statements. Actual results may differ materially from Actavis' current expectations depending upon a number of factors affecting Actavis' 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 Actavis' products; difficulties or delays in manufacturing; and other risks and uncertainties detailed in Actavis' periodic public filings with the Securities and Exchange Commission, including but not limited to Actavis' Quarterly Report on Form 10-Q for the quarter ended September 30, 2014. Except as expressly required by law, Actavis disclaims any intent or obligation to update these forward-looking statements.

CONTACTS: Investors:
Lisa DeFrancesco
(862) 261-7152

Media:
Charlie Mayr
(862) 261-8030

David Belian
(862) 261-8141

SOURCE Actavis plc

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