New Study Demonstrates Clinical Efficacy of Telithromycin Superior to Standard First-Line Antibiotic Therapy for Treatment of Mild to Moderate Community-Acquired Pneumonia (CAP)
San Diego, CA
May 24, 2005

Data presented today at the annual International Conference of the American Thoracic Society in San Diego, California - USA, from the Community-acquired pneumonia Outcome in high Bacterial Resistance Areas (COBRA) study, a randomized clinical superiority trial, showed that the clinical efficacy of telithromycin (marketed as KETEKÒ) in outpatients with CAP is superior to that of local standard first line oral antibiotic therapy in areas with a high prevalence of penicillin or macrolide-resistant Streptococcus pneumoniae.  The clinical cure rate with telithromycin  was 7.2 percent higher than the overall clinical cure rate with comparator antibiotics (see detailed results below).

“The clinical cure rates achieved in this study support the use of telithromycin as first line oral therapy for patients with (mild to moderate) community-acquired pneumonia and therefore may have important implications for decision making in everyday clinical practice”, said Professor C. Mayaud from the Service de Pneumologie/ Réanimation Respiratoire of Hôpital Tenon, Paris - France. “Even if this study was not powered to show significant differences by patient sub-group, comparator sub-groups, or causative pathogen, it may signal that there are clinical benefits in treating CAP with an antibiotic that is active against both antibiotic-resistant pneumococci and atypical pathogens.”

About the study
The COBRA study is a Phase IV clinical trial designed to compare the efficacy and safety of telithromycin to other standard, single agent antibiotics, such as b-lactams, cephalosporins, macrolides, and quinolones, in outpatients with mild to moderate CAP in areas with a high prevalence of penicillin and erythromycin-resistant S. pneumoniae isolates (erythromycin resistance rate >30 percent).  The study enrolled 505 patients from Italy, Spain, Taiwan, Korea, Hong Kong, Hungary, Thailand, South Africa, Singapore, Tunisia, and Greece and was completed in June 2004.

Outpatients with clinical and radiological evidence of CAP were centrally randomized to receive either telithromycin 800 mg for 7-10 days or other standard first line oral antibiotic therapy (chosen by investigators in line with local treatment guidelines).  Clinical efficacy was assessed by the investigators post-therapy (Day 17-21) and reviewed by 3 independent experts blinded to treatment groups.  Clinical failure was defined as subsequent antibiotic treatment for lower respiratory tract infection or CAP-related fever post-therapy.

A total of 505 patients were enrolled; 482 were included in the modified intent to treat (mITT) efficacy analysis. In the comparators group (CMP), 39 percent of patients received macrolides, 44 percent b-lactams, and 17 percent fluoroquinolones. Overall clinical cure rates in the telithromycin (TEL) group were significantly higher than those in the CMP group:

Post-therapy clinical cure rate

Population TEL
% (n/N)
CMP
% (n/N)
Difference, 95%CI p-value
mITT (Primary analysis) 86.0% (208/242) 78.8% (189/240) 0.004, 0.140 0.042
mITT (Expert-validated)a 92.1% (223/242) 85.8% (206/240) 0.008, 0.119 0.029

In the subgroup of patients with documented pneumococcal CAP, clinical cure rates were 90.7 percent (39/43) for TEL vs. 76.3 percent (39/51) for CMP.  Both treatments were similarly well tolerated.

Pneumonia is the leading infectious disease cause of death in the elderly and remains one of the top five causes of mortality in persons 65 of age and older.  In the US alone, there are between 2-3 million cases of CAP every year resulting in approximately 10 million physician visits, 500,000 hospitalizations and 45,000 deaths.  The overall cost for treating patients with CAP is more than $23 billion per year.  Patient compliance with antibiotic regimens is poor within the community; decreasing the frequency and duration of dosing may improve compliance.

About Ketek
Ketek, the first in a new class of antibiotics known as the ketolides, was first launched in the United States in 2004.  

Ketek tablets (800 mg once daily) are indicated for the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions listed below for patients 18 years old and above.
Acute bacterial exacerbation of chronic bronchitis (AECB) due to Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis. – five-day regimen
Acute bacterial sinusitis due to Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis or Staphylococcus aureus. – five-day regimen
Community acquired pneumonia (CAP) (of mild to moderate severity) due to Streptococcus Pneumoniae (including multi-drug resistant isolates), Haemophilus influenzae, Moraxella catarrhalis, Chlamydophila pneumoniae or Mycoplasma pneumoniae. – seven- to 10-day regimen

Ketek works differently than other antibiotics by binding strongly to two sites on the bacterial ribosome, stopping protein production and eradicating the targeted bacteria.  

This strong dual binding helps provide coverage against resistant strains of S. pneumoniae in vitro.  

Important Safety Information
Ketek is contraindicated in patients taking cisapride or pimozide and in patients with a history of hypersensitivity to telithromycin or any macrolide antibiotic.

Exacerbations of myasthenia gravis have been reported in patients with myasthenia gravis treated with Ketek. Ketek is not recommended in patients with myasthenia gravis.

Ketek has the potential to prolong the QTc interval of the electrocardiogram in some patients. QTc prolongation may lead to an increased risk for ventricular arrhythmias, including torsades de pointes. Thus, Ketek should be avoided in patients with congenital prolongation of the QTc interval, and in patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and in patients receiving Class IA (eg, quinidine and procainamide) or Class III (eg, dofetilide) antiarrhythmic agents.

Ketek may cause visual disturbances particularly in slowing the ability to accommodate and the ability to release accommodation. Visual disturbances included blurred vision, difficulty focusing, and diplopia.

Hepatic dysfunction, including increased liver enzymes and hepatitis, with or without jaundice, has been reported with the use of Ketek. Caution should be used in patients with a previous history of hepatitis/jaundice associated with the use of Ketek.

Use of simvastatin, lovastatin, or atorvastatin concomitantly with Ketek should be avoided. If Ketek is prescribed, therapy with simvastatin, lovastatin, or atorvastatin should be suspended during the course of treatment. Concomitant treatment of Ketek with rifampin, a CYP 3A4 inducer, should be avoided.

Most adverse events greater than two percent were mild to moderate and included diarrhea, nausea, headache, dizziness, vomiting and loose stools.

For additional important information, visit www.ketek.com.


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Sanofi-aventis Group is the world’s third largest pharmaceutical company, ranking number one in Europe. Backed by a world-class R&D organization, sanofi-aventis is developing leading positions in seven major therapeutic areas: cardiovascular, thrombosis, oncology, metabolic diseases, central nervous system, internal medicine, and vaccines. The sanofi-aventis Group is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY)

The sanofi-aventis Group conducts its business in the United States through its subsidiaries Sanofi-Synthélabo Inc., Aventis Pharmaceuticals Inc. and Sanofi Pasteur Inc.

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U.S. Contact
Melissa Feltmann, +1 908-243-7080, melissa.feltmann@sanofi-aventis.com.