1 Copyright: W. Michael Scheld, M.D.

2 Infectious Diseases Society of America (IDSA) – Antimicrobial Availability Task Force (AATF) W. Michael Scheld, MD University of Virginia March 2004

3 IDSA/PhRMA/FDA Workshop; November 2002: Themes “Delta” Antibacterial resistance increasing Antibacterial R&D declining PK/PD; surrogate endpoints AECB; meningitis; HAP

4 The perception YEARS Antibacterial resistance Antibacterial R&D.

5

6 Threats to antibacterials Bacterial resistance Drug shortages Dry pipeline Void in public policy

7 Antimicrobial Research and Development Spellberg et al

8 New Antibacterials Approved ( )

9 In 2002, out of 89 new drugs, no new antibacterial drugs were approved. Only about 5 new antibacterials in the drug pipeline, out of more than 400 agents in development* *According to annual reports of 15 major pharmaceutical companies Antimicrobial Availability

10 New Antibacterial Agents Approved Since 1998 Spellberg et al ANTIBACTERIAL rifapentine quinupristin/dalfopristin moxifloxacin gatifloxacin linezolid cefditoren pivoxil ertapenem gemifloxacin daptomycin YEAR NOVEL No Yes No Yes

11 Phase III antibacterial development, December 2003 (NDA Pipeline; “pink sheet”) ABT-773 Afelimomab Tigecycline (vs 18 novel oncology agents)

12 IOM report, 2003 “Unfortunately, complacency toward infections diseases in the 1960’s, overconfidence in existing antibiotics, and competition from highly profitable opportunities for pharmaceutical development and sale in other fields of medicine resulted in a lag in the production of new classes of antibodies. This occurred despite significant advances in the fundamental science that has fueled pharmaceutical innovation in many other areas”

13 IDSA Antimicrobial Availability Task Force Charge “Develop novel public policy to ensure a sustainable supply of safe and effective antimicrobial drugs to protect public health”

14 TASK FORCE MEMBERS John G. Bartlett, MD, Chair John Hopkins Univ. SOM Baltimore, MD Johns S. Bradley, MD Children’s Hospital-San Diego San Diego, CA John E. Edwards, MD Harbor/UCLA School of Medicine Torrance, CA David N. Gilbert, MD Providence Portland Medical Center Portland, OR W. Michael Scheld, MD University of Virginia Medical Center Charlottesville, VA David M. Shlaes, MD Idenix – ID Research Cambridge, MA George H. Talbot, MD Talbot Advisors Wayne, PA Francis P. Tally, MD Cubist Pharmaceuticals, Inc Lexington, MA David B. Ross, MD Food and Drug Administration Rockville, MD John H. Powers, MD Food and Drug Administration Rockville, MD

15 IDSA – AATF Work plan Understand the problem Publish research; findings Discuss with stakeholders “Field trips” Produce “white paper” Develop solutions

16 The Public Health Service Action Plan to combat antimicrobial resistance (CDC, NIH, FDA, etc.) October 2001 Stimulate development priority products to combat antimicrobial resistance Streamline regulatory process Identify incentives for development

17 Defining the Problem: “Bad Bugs, No Drugs” Input sought from major stakeholders: –IDSA’s membership base of 7,500 physicians, researchers, and health care providers –FDA –CDC, NIAID, HHS –Senior pharmaceutical executives –Venture capital companies –Legislators

18 Defining the Problem: “Field Trips” Abbott NIAID BMS HHS GSKCDC Novartis FDA Pfizer Congress Vicuron Others, including venture capital

19 Placebo-controlled trial of AECB IDSA, ATS joint task force Develop protocol and budget Implement network Submit to NIAID for funding