1. Ketek ™ (Telithromycin) NDA 21-144 Efficacy Review John Alexander, M.D., M.P.H. Medical Team Leader Division of Anti-Infective Drug Products

2. Outline Indications –Original NDA Studies –Resubmission Studies Drug-Resistant Streptococcus pneumoniae –Penicillin Resistance –Erythromycin Resistance

3. Indications Acute Exacerbation of Chronic Bronchitis Acute Sinusitis Community-Acquired Pneumonia Tonsillitis/Pharyngitis

4. 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

5. Acute Exacerbation of Chronic Bronchitis

8. 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

9. Acute Sinusitis

11. 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

12. Community-Acquired Pneumonia

15. 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

16. 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)

17. CAP: Drug-Resistant S. pneumoniae Telithromycin MIC

18. 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

19. CAP: Drug-Resistant S. pneumoniae

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 Non-evaluable Patients –5 Successes –2 Failures –5 Indeterminate Withdrawn for Elevated BUN/CR on Day 6 Bronchitis at TOC visit, Aspiration on Day 5, New Antibiotics on Day 3 (AE and baseline bacteremia), Withdrawal for Personal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

21. 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

22. CAP: Drug-Resistant S. pneumoniae Bacteremia Patients

23. CAP: Drug-Resistant S. pneumoniae Cases from Japanese Studies

24. 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

25. AS: Drug-Resistant S. pneumoniae

26. 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