NEW YORK--()--Forest Laboratories, Inc. (NYSE: FRX) announced today that TeflaroTM (ceftaroline fosamil), a broad-spectrum bactericidal cephalosporin with activity against both gram-positive and gram-negative microorganisms, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of community-acquired bacterial pneumonia (CABP), including cases caused by Streptococcus pneumoniae bacteremia, and acute bacterial skin and skin structure infection (ABSSSI), including cases caused by methicillin-resistant Staphylococcus aureus (MRSA). The efficacy and safety of Teflaro was established in pivotal trials including 1219 patients treated with the drug.
“Forest recognizes the enormous burden of disease associated with community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections, and we are extremely pleased to see that our first product in this category has obtained approval for both of these disease indications”
Teflaro is a member of the cephalosporin class of antibiotics, the most frequently prescribed class of antibiotics in the world. Forest expects Teflaro to be available to wholesalers by January 2011.
“Forest recognizes the enormous burden of disease associated with community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections, and we are extremely pleased to see that our first product in this category has obtained approval for both of these disease indications,” said Dirk Thye, President of Cerexa, a wholly-owned subsidiary of Forest Laboratories, Inc. “We eagerly anticipate the commercial launch of Teflaro and remain committed to bringing additional new treatments to market that target infectious diseases.”
Howard Solomon, Chairman and Chief Executive Officer of Forest said, “Our success in gaining approval for Teflaro is a significant milestone for our new anti-infective franchise. Achieving a first cycle approval from the FDA is a tribute to the excellent design and execution of a complex clinical development program as well as the virtues of the product itself. Teflaro is the fourth new drug approval in the last three years from the fourth different division of the FDA. We are very proud of all of our Forest colleagues who have contributed to Teflaro’s acquisition, development and approval. We look forward to providing more treatment options for healthcare providers and patients in the future.”
FOCUS I and FOCUS II Phase 3 Clinical Study Results
FOCUS I and FOCUS II studied adult patients who were hospitalized with moderate to severe CABP requiring treatment with intravenous antimicrobials.
To evaluate the treatment effect of Teflaro, a responder analysis was conducted in CABP patients. A responder was defined as a patient who on Day 4 of therapy was in stable condition based on accepted clinical criteria; this was defined as normalization of vital signs and improvement from baseline on at least one respiratory symptom (cough, dyspnea, pleuritic chest pain, or sputum production) while not worsening on any of these four respiratory symptoms. This analysis of the pivotal trial data served as an important element of the FDA’s efficacy evaluation.
In FOCUS I, Teflaro-treated patients had a response rate of 69.6% compared with a response rate of 58.3% for ceftriaxone-treated patients on Day 4. In FOCUS II, Teflaro-treated patients had a response rate of 69% compared with a response rate of 61.4% for ceftriaxone-treated patients on Day 4.
The protocol-specified analyses included clinical cure rates at the test of cure (TOC; 8-15 days after end of therapy). In FOCUS I, Teflaro-treated patients had a clinical cure rate of 86.6% compared with a rate of 78.2% in ceftriaxone-treated patients in the clinically evaluable (CE) population. In FOCUS II, Teflaro treated-patients had a clinical cure rate of 82.3% compared with a rate of 77.1% in ceftriaxone-treated patients in the CE population.
CANVAS I and CANVAS II Phase 3 Clinical Study Results
The CANVAS I and CANVAS II trials evaluated Teflaro monotherapy versus vancomycin plus aztreonam in adult patients with complicated skin and skin structure infections caused by gram-positive and gram-negative bacteria.
To evaluate the treatment effect of Teflaro, a responder analysis was conducted in ABSSSI patients with either a major abscess with ≥ 5 cm of surrounding erythema, wound infection, or deep/extensive cellulitis requiring treatment with IV antimicrobials. A responder was defined as a patient who on Day 3 achieved both cessation of lesion spread and absence of fever.
In CANVAS I, Teflaro-treated patients had a response rate of 74% compared with a response rate of 64.6% for vancomycin plus aztreonam-treated patients on Day 3. In CANVAS II, Teflaro-treated patients had a response rate of 74% compared with a response rate of 68.1% for vancomycin plus aztreonam-treated patients on Day 3. This analysis of the pivotal trial data served as an important element of the FDA’s efficacy evaluation.
The protocol-specified analyses included clinical cure rates at the TOC (8-15 days after the end of therapy). In CANVAS I, Teflaro-treated patients had a clinical cure rate of 91.1% compared with a rate of 93.3% in vancomycin/aztreonam-treated patients in the CE population. In CANVAS II, Teflaro-treated patients had a clinical cure rate of 92.2% compared with a rate of 92.1% in vancomycin/aztreonam-treated patients.
Each of the studies also indicated that Teflaro was well-tolerated. The overall rate of adverse events was comparable between the two treatment groups. The overall discontinuation rate for Teflaro-treated patients was 2.7% compared to a rate of 3.7% for the comparator group-treated patients. The most common adverse reactions occurring in > 2% of patients receiving Teflaro in the pooled Phase 3 clinical trials were diarrhea, nausea, and rash.
About TeflaroTM (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 (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.
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
Known serious hypersensitivity to Teflaro or other members of the cephalosporin class. Anaphylaxis and anaphylactoid reactions have been reported with ceftaroline.
Warnings and Precautions
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.
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
For pregnant or nursing mothers, ceftaroline fosamil should only be used if the potential benefit outweighs the potential risk to the fetus or child.
Safety and effectiveness in pediatric patients has not been studied.
Because elderly patients ≥ 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 as in younger patients with impaired renal function
Dosage adjustment is required in patients with moderately (30 to ≤ 50 mL/min) or severely (< 30 mL/min) impaired renal function
The pharmacokinetics of ceftaroline in patients with hepatic impairment have not been established
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.
About CABP Requiring Hospitalization
In 2007, pneumonia was the eighth leading cause of death in the United States and the number-one cause of death from infectious diseases.1 The cost of care for patients with CABP in the U.S. has been estimated to be more than $10 billion annually.
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 2005.2
About Forest Laboratories
Forest Laboratories’ (NYSE: FRX) longstanding global partnerships and track record developing and marketing pharmaceutical products in the United States have yielded its well-established central nervous system and cardiovascular franchises and innovations in anti-infective medicine. The Company’s pipeline, the most robust in its history, includes product candidates in all stages of development across a wide range of therapeutic areas. The Company is headquartered in New York, NY. To learn more, visit www.FRX.com.
Except for the historical information contained herein, this release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements involve a number of risks and uncertainties, including the difficulty of predicting FDA approvals, the acceptance and demand for new pharmaceutical products, the impact of competitive products and pricing, the timely development and launch of new products, and the risk factors listed from time to time in Forest Laboratories' Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and any subsequent SEC filings.
1 Xu J National vital Statistics Reports, Vol.58, No.1 2009, p18.
2 Klevens R, Morrison M, Nadle J et al. Invasive Methicillin-Resistant Staphylococcus aureus Infections in the United States. Journal of the American Medical Association. 2007; 298(15):1763-1771