Ketek

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Ketek (Telithromycin) NDA 21-144 Efficacy Review

• John Alexander, M.D., M.P.H.
• Medical Team Leader
• Division of Anti-Infective Drug Products

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Outline

• Indications
• Original NDA Studies
• Resubmission Studies
• Drug-Resistant Streptococcus pneumoniae
• Penicillin Resistance
• Erythromycin Resistance

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Indications

• Acute Exacerbation of Chronic Bronchitis
• Acute Sinusitis
• Community-Acquired Pneumonia
• Tonsillitis/Pharyngitis

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Acute Exacerbation of Chronic Bronchitis

• Two Studies with the Original NDA
• Study 3003
• Telithromycin for 5 days
• Amox/Clav 500mg/125mg TID for 10 days
• Study 3007
• Telithromycin for 5 days
• Cefuroxime Axetil 500 mg BID for 10 days
• One Study in the Resubmission
• Study 3013
• Telithromycin for 5 days
• Clarithromycin 500 mg BID for 10 days

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Acute Exacerbation of Chronic Bronchitis
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Acute Exacerbation of Chronic Bronchitis
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Acute Exacerbation of Chronic Bronchitis
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Acute Sinusitis

• Three Studies with 1st Review Cycle
• Study 3002
• Telithromycin for 5 days or 10 days, uncontrolled
• Study 3005
• Telithromycin for 5 days or 10 days
• Amox/Clav 500mg/125mg TID for 10 days
• Study 3011
• Telithromycin for 5 days
• Cefuroxime Axetil 250 mg BID for 10 days
• No New Studies in the Resubmission

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Acute Sinusitis
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Acute Sinusitis
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Community-Acquired Pneumonia

• Original NDA Studies
• Study 3001
• Telithromycin for 10 days
• Amoxicillin 1g TID for 10 days
• Study 3006
• Telithromycin for 10 days
• Clarithromycin 500 mg BID for 10 days
• Study 3009
• Telithromycin for 7-10 days
• Trovafloxacin 200 mg QD for 7-10 days
• Open-Label Studies 3000, 3009OL, 3010

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Community-Acquired Pneumonia
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Community-Acquired Pneumonia
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Community-Acquired Pneumonia
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Community-Acquired Pneumonia

• New Studies in the Resubmission
• Study 4003
• Telithromycin for 5 days or 7 days
• Clarithromycin 500 mg BID for 10 days
• Study 3012
• Open-label, Telithromycin for 7 days
• Japanese Studies
• Study 3107 and Study 2105

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Drug-Resistant S. pneumoniae

• Clinical Cases with DRSP Collected from CAP and
  AS Studies
• Penicillin Resistance (MIC ? 2?g/mL)
• Erythromycin Resistance (MIC ? 1?g/mL)

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CAP Drug-Resistant S. pneumoniaeTelithromycin
MIC
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CAP Drug-Resistant S. pneumoniae

• A Total of 49 Cases of CAP due to DRSP from
  Western Studies
• Subset of Bacteremic Cases
• Additional Cases from Japanese Trials

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CAP Drug-Resistant S. pneumoniae
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CAP Drug-Resistant S. pneumoniae

• Non-evaluable Patients
• 5 Successes
• 2 Failures
• 5 Indeterminate
• Withdrawn for Elevated BUN/CR on Day 6
• Bronchitis at TOC visit, Aspiration on Day 5, New
  Antibiotics on Day 3 (AE and baseline
  bacteremia), Withdrawal for Personal Reasons

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CAP Drug-Resistant S. pneumoniae

• All PRSP
• 19/27 (70.4) in MITT, 1 Indeterminate
• All ERSP
• 29/37 (78.4) in MITT
• 7 Comparator Patients with DRSP
• 2 Isolates Susceptible to Comparator Agent
• 3/5 in Clarithromycin Patients with ERSP

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CAP Drug-Resistant S. pneumoniaeBacteremia
Patients
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CAP Drug-Resistant S. pneumoniaeCases from
Japanese Studies
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AS Drug-Resistant S. pneumoniae

• A Total of 29 Cases of Acute Sinusitis due to
  DRSP
• Includes both 5-day and 10-day Duration
• All cases from Studies in Original NDA

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AS Drug-Resistant S. pneumoniae
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Acknowledgments

• Statistical
• Thamban Valappil, Ph. D.
• George Rochester, Ph. D.
• Clinical
• Alma Davidson, M. D.
• Janice Soreth, M. D.
• Project Management
• Judit Milstein
• Ketek Review Team