# Presentation: 934234

## KetekTM (Telithromycin) NDA 21-144 Efficacy Review

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

## Outline

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

## Indications

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

## 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

## Acute Exacerbation of Chronic Bronchitis

## Acute Exacerbation of Chronic Bronchitis

## Acute Exacerbation of Chronic Bronchitis

## 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

## Acute Sinusitis

## Acute Sinusitis

## 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

## Community-Acquired Pneumonia

## Community-Acquired Pneumonia

## Community-Acquired Pneumonia

## 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

## 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)

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

## 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

## CAP: Drug-Resistant S. pneumoniae

## 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

## 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

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

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

## 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

## AS: Drug-Resistant S. pneumoniae

## 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