# Presentation: 772058

## IDSA / ISAP / FDA Workshop on Antimicrobial Drug DevelopmentUpdate 2004

- Edward Cox, MD MPH
- ODE IV
- Center for Drug Evaluation and Research
- US Food and Drug Administration
- April 15, 2004

## Update 2004 - Outline

- Scientific meetings
- Guidance development
- Work with Focus Technologies database
- Criteria for resistant pathogens of public health importance
- Critical path initiative
- Preserving the utility of existing antimicrobial agents

## Scientific Meetings - 1

**March 4****th**** and 5****th****, 2003 - FDA Anti Infective Drug Products Advisory Committee**
**Patterns of antimicrobial resistance in *****Streptococcus pneumoniae***** and drug labeling**
**Science-based resistant pathogen claims**
**Use of data from Focus Technologies contract**
**High rate of cross resistance between penicillin resistant strains and other classes of drugs – multi-drug resistant *****Streptococcus pneumoniae *****(MDRSP)**
**Developing criteria for resistant pathogens of public health importance**
**Relating clinical data from one disease to another**

## Evaluating Cross-Resistance

**Drug Y**

**Drug X**

**S, S**

**S, I**

**S, R**

**I, S**

**I, I**

**I, R**

**R, S**

**R, I**

**R. R**

**MIC **

## Correlations in MIC Distributions between Penicillin and Cefuroxime Tested against S. pneumoniae (2000 – 2002)

**Total n = 9,779**
**Levo R isolates: n = 87; 26.4% Pen S; 42.5% Pen I; 31.0% Pen R**

**Total n = 5387**

## Correlations in MIC Distributions between Levofloxacin and Penicillin Tested against S. pneumoniae (2000-2002)

**Total n = 9,779**
**Levo R isolates: n = 87; 26.4% Pen S; 42.5% Pen I; 31.0% Pen R**

## Scientific Meetings - 2

**March 4****th**** and 5****th****, 2003 - FDA Anti Infective Drug Products Advisory Committee**
**Patterns of antimicrobial resistance in *****Streptococcus pneumoniae***** and drug labeling**
**Developing criteria for resistant pathogens of public health importance**
**Criteria refined for resistant pathogens of public health importance in a particular indication**
**The pros and cons of a list were discussed**
**Relating clinical data from one disease to another**

## Criteria for Resistant Pathogen/ Indications of Public Health Importance

**Limited available therapies due to multi-drug resistance of the organism**
**Organism causes serious and severe disease**
**Drug to which organism is resistant is commonly used in disease under study**
**Organism of sufficient prevalence in population with disease under study**
**Drug used to control spread of disease in population **
**Clinical correlation of *****in vitro *****resistance with poor clinical outcomes**

## How to Use the Criteria

**Pathogen would not need to fulfill all of criteria to be a resistant pathogen of public health importance in a particular indication**
**Drug sponsors would need clinical data on treatment of resistant pathogens in the indication of interest**
**differences in patient characteristics of those with resistant organisms vs. susceptible organisms**
**Priority review based upon results of clinical trials**
**Note that a drug may still be approved but not garner resistant pathogen claim until sufficient clinical data on the resistant pathogen of interest have been accrued**

## Previously Granted Resistance Claims

**Methicillin resistant *****S. aureus *****(MRSA)**
**vancomycin in serious infections**
**linezolid in HAP and cSSSI**
**Vancomycin resistant *****E. faecium *****(VRE)**
**linezolid**
**dalfopristin-quinupristin in bacteremia**
**Penicillinase-producing staphylococci**
**nafcillin in serious and severe infections**
**Beta-lactamase producing *****H. influenzae***** and *****Moraxella catarrhalis***
**number of infections with cephalosporins**
**Penicillin resistant *****S. pneumoniae***** (PRSP)**
**levofloxacin and moxifloxacin in CAP**
**Multi-drug resistant *****S. pneumoniae *****(MDRSP)**
**gemifloxacin, telithromycin in CAP**

## Scientific Meetings - 3

**March 4****th**** and 5****th****, 2003 - FDA Anti Infective Drug Products Advisory Committee**
**Patterns of antimicrobial resistance in *****Streptococcus pneumoniae***** and drug labeling**
**Developing criteria for resistant pathogens of public health importance**
**Relating clinical data from one disease to another **
**Discussion of the role of using data from one indication to support another indication**
**Similar microbial etiologies**
**Similar tissue distribution**
**Consider severity disease of one illness to another**
**Consideration of host factors**

## Scientific Meetings - 4

**September 2003 - BAMSG/FDA workshop on fungal drug development**
**Clinical trial design for empiric antifungal therapy in febrile neutropenic patients**
**Clinical trial design for investigating combination antifungal therapy**
**October 2003 FDA AIDP Advisory Committee**
**Acute Bacterial Sinusitis**
**Diabetic Foot Infections**

## Scientific Meetings - 5

**September 2003 - BAMSG/FDA workshop on fungal drug development**
**October 2003 FDA AIDP Advisory Committee**
**Clinical trial design for Diabetic Foot Infections**
**Defining the condition**
**Microbiologic diagnosis in patients with DFI**
**Measuring outcomes**
**Clinical trial design in Acute Bacterial Sinusitis**
**Enriching the population for patients with bacterial sinusitis **
**Role of microbiologic diagnosis**
**Superiority trial designs – active + other symptomatic therapies vs. symptomatic therapies or dose-response**

## Guidance Development

**Updating and Developing New Guidance Documents**
- Acute Bacterial Sinusitis
- Acute Bacterial Exacerbation of Chronic
-  Bronchitis
- Acute Otitis Media
- Acute Bacterial Meningitis
- Drug Development for Resistant Pathogens

## Critical Path Initiative

**Critical Path white paper issued March 2004**
**Recognizes the advances in the basic biomedical sciences and the high costs of bringing a new medicine to market**
**Calls for advances in the applied sciences in medical product development – A better product development toolkit**
**Tools for assessing safety**
**Tools for demonstrating medical utility**
**Tools for characterization and manufacturing**
**Addressing the critical path initiative will require the joint efforts of academia, industry, and FDA**

- http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.pdf

## Preserving the Utility of Existing Antimicrobial Drugs - 1

**Final rule - *****Labeling Requirements for Systemic Antibacterial Drug Products Intended for Human Use***
** ****Issued February 6, 2003**
** ****Effective February 6, 2004**
** ****Includes statements in labeling about using systemic antibacterial drugs in a way that will reduce the rate of development of antimicrobial resistance and to encourage physicians to counsel their patients about the use of antibacterial drugs**
-  **Estimated to impact 669 systemic antibacterial drug product labels**

- http://www.fda.gov/OHRMS/DOCKETS/98fr/03-2969.pdf

## Preserving the Utility of Existing Antimicrobial Drugs - 2

**FDA is a co-sponsor of the GetSmart Program with CDC**
**Education/Outreach Program**
**Includes television, radio and print public service announcements **
**Goal is to better inform Americans about when antibiotic treatment is warranted** ** **
**Campaign launched fall 2003 at ICAAC**

- http://www.fda.gov/cder/consumerinfo/antibiot-resist-brochure.htm
- http://www.cdc.gov/drugresistance/community/default.htm#campaign

## Summary - Update 2004

- Scientific meetings on labeling issues and clinical trial design for a number of indications
- Drug labeling for resistant *S. pneumoniae*
- Criteria for resistant pathogens of public health importance
- Relating clinical data from one disease to another
- Trial design for studies of empiric antifungal therapy for febrile neutropenic patients and combination antifungal therapy
- Trial design for DFI and ABS
- Guidance development
- Critical path initiative
- Preserving the utility of existing antimicrobial agents

## Slide 19