TYGACIL Receives FDA approvable Letter Pneumonia Treatment

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Wyeth Pharmaceuticals announced that FDA has issued an approvable letter for the first-in-class antibiotic TYGACIL (tigecycline) for the treatment of adult patients with community-acquired pneumonia (CAP).

Before granting approval, the FDA requested that Wyeth provide additional analyses to support the safety and efficacy of TYGACIL for the treatment of patients with CAP with illness severe enough to require hospitalization, including those who are at higher risk of mortality.

In addition, the FDA requested information regarding the benefit/risk of TYGACIL for any potential of liver toxicity. Wyeth recently provided that information to the agency during the review period and believes that its response adequately addresses the issues raised by the FDA. However, the agency acknowledged in its letter that it had not yet reviewed that information.

"We believe the data from our current clinical development program support TYGACIL as a potential therapeutic option for patients with CAP," says Gary L. Stiles, M.D., Executive Vice President, Chief Medical Officer, Wyeth Pharmaceuticals. "Wyeth is committed to working with the FDA to resolve the outstanding issues for TYGACIL in order to gain approval."

TYGACIL was approved by the FDA in June 2005 for the treatment of adult patients with complicated intra-abdominal infections (cIAI) and complicated skin and skin structure infections (cSSSI).

Wyeth has achieved significant success in bringing new products to market. Year to date, the Company has obtained three new product approvals in the following therapeutic areas: major depressive disorder, Hemophilia A and opioid-induced constipation.

About Community-Acquired Pneumonia

CAP is defined as pneumonia acquired outside a hospital or long-term care facility. It is an infection of the lungs that results in decreased ability to function normally. Although pneumonia is not a reportable illness, it appears that up to 5.6 million cases of community-acquired pneumonia occur annually. In addition, hospitalization rates among patients with CAP are approximately 20 percent. Symptoms of CAP include cough, fever, chills, fatigue, shortness of breath, and chest pain.

TYGACIL was evaluated in adults for the treatment of CAP in two phase 3, multicenter, randomized, double-blind studies. The two studies (N=418, N=434) were conducted at 116 sites in 28 countries across the globe and evaluated the efficacy and safety of tigecycline compared with levofloxacin in subjects hospitalized with CAP.

TYGACIL is indicated for the treatment of adults with:

Complicated skin and skin structure infections (cSSSI) caused by Escherichia coli, Enterococcus faecalis (vancomycin-susceptible isolates only), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus agalactiae, Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Streptococcus pyogenes, and Bacteroides fragilis.

Complicated intra-abdominal infections (cIAI) caused by Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (vancomycin-susceptible isolates only), Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros.

TYGACIL can be used as an empiric monotherapy to treat a variety of cIAI and cSSSI, both hospital- and community-acquired, including complicated appendicitis, intra-abdominal abscesses, infected burns, deep soft-tissue infections, and infected ulcers.

TYGACIL, a first-in-class glycylcycline, is an IV antibiotic with an expanded broad spectrum of in vitro activity against gram positives, gram negatives, anaerobes, methicillin-resistant and -susceptible Staphylococcus aureus (MRSA and MSSA) and vancomycin-resistant enterococci (VRE); TYGACIL is unaffected by extended-spectrum beta-lactamases (ESBLs).

In addition, TYGACIL has been shown to have in vitro activity against the following organisms: Enterococcus avium, Enterococcus casseliflavus, Enterococcus faecalis (vancomycin-resistant isolates), Enterococcus faecium (vancomycin-susceptible and -resistant isolates), Enterococcus gallinarum, Listeria monocytogenes, Staphylococcus epidermidis (methicillin-susceptible and -resistant isolates), Acinetobacter baumannii, Aeromonas hydrophila, Citrobacter koseri, Enterobacter aerogenes, and Pasteurella multocida. The clinical significance of in vitro activity is unknown.

TYGACIL provides clinicians with an expanded broad-spectrum antibiotic option that can be used at the onset of treatment when the specific bacteria present are not yet known. In addition, TYGACIL does not require dosage adjustment in patients with impaired renal function, and is conveniently dosed every 12 hours.

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Important Safety Information

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

-- Anaphylaxis/anaphylactoid reactions have been reported with nearly all antibacterial agents, including tigecycline, and may be life-threatening

-- TYGACIL is contraindicated in patients with known hypersensitivity to tigecycline

-- TYGACIL should be administered with caution in patients with known hypersensitivity to tetracycline class antibiotics

-- Glycylcycline class antibiotics are structurally similar to tetracycline class antibiotics and may have similar adverse effects. Such effects may include: photosensitivity, pseudotumor cerebri, and anti-anabolic action (which has led to increased BUN, azotemia, acidosis, and hyperphosphatemia). As with tetracyclines, pancreatitis has been reported with the use of TYGACIL

-- The safety and efficacy of TYGACIL in patients with hospital-acquired pneumonia have not been established

-- In clinical trials, the most common treatment-emergent adverse events in patients treated with TYGACIL were nausea (26.4%) and vomiting (18.1%)

-- TYGACIL may cause fetal harm when administered to a pregnant woman

-- The safety and effectiveness of TYGACIL in patients below age 18 and lactating women have not been established

-- Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including TYGACIL, and may range in severity from mild diarrhea to fatal colitis

-- Concurrent use of antibacterial drugs with oral contraceptives may render oral contraceptives less effective

-- The use of TYGACIL during tooth development may cause permanent discoloration of the teeth. TYGACIL should not be used during tooth development unless other drugs are not likely to be effective or are contraindicated

-- Prothrombin time or other suitable anticoagulant test should be monitored if TYGACIL is administered with warfarin

-- Monotherapy should be used with caution in patients with clinically apparent intestinal perforation

-- In patients with severe hepatic impairment (Child Pugh C), the initial dose of TYGACIL should be 100 mg followed by 25 mg every 12 hours. Patients should be treated with caution and monitored for treatment response

-- The following drugs should not be administered simultaneously through the same Y-site as TYGACIL: amphotericin B and diazepam.

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