# Presentation: 349883

## FDA – IDSA - ISAP WorkshopApril 15, 2004

- Continuing Discussion on Incentives
- George H. Talbot MD
- On Behalf of the AATF

- 13 Apr 04

## Presentation Objectives

- Update workshop attendees on AATF’s efforts to clarify factors responsible for decreased antibacterial R&D
- Discuss the full range of possible solutions... not just “financial” incentives

- 13 Apr 04

## What has AATF Learned?Overview

- There is a problem
- Complex, multifactorial etiology
- Susceptible to oversimplification: “If only....”
- No easy, single solution
- Potential approaches are apparent
- Progress requires
- Long-term commitment
- Active collaboration of essential partners

- 13 Apr 04

## The Problem

- “Drug options for treatment of infections are becoming increasingly limited, largely as a result of growing antimicrobial resistance.  Many generic but essential antibiotics are in short supply, and the development of new antibiotics has been severely curtailed.... *Only 4 large pharmaceutical companies with antibiotic research programs remained in existence in 2002....”*  				(Institute of Medicine Report, 2003)

- 13 Apr 04

## The ProblemTotal Approved Antibacterials: US

- Spellberg et al, CID 2004 in press

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## What has AATF Learned?Interactions with Stakeholders

- Pharmaceutical companies
- VCs
- FDA
- CDC, NIAID, HHS
- The scientific and lay press
- Congress

- 13 Apr 04

## What Has AATF Learned? Issues for Pharma

- Many individuals and groups within pharma are deeply concerned about, and committed to, the future of anti-bacterial R&D
- “Big” pharma is becoming disengaged
- There are notable exceptions
- Greatest concern -- the dearth of resources being applied at the Discovery level

- 13 Apr 04

## What Has AATF Learned? Issues for “Big” Pharma

- “Big” Pharma sees better return from the treatment of chronic diseases.
- In contrast, antibacterial therapies are:
- Costly to develop
- Short course, used for acute illnesses
- Not embraced by the marketplace (cost, resistance, “satisfied” market)
- Rarely “blockbusters”

- 13 Apr 04

## What Has AATF Learned? Issues for “Big” Pharma

- Any further uncertainty is a disincentive
- Further IP protections - ? upside
- Tax credits – interesting
- Because of enormous hurdles for Discovery infrastructure, we must keep those companies that are “In” – “In”

- 13 Apr 04

## What Has AATF Learned?Issues for “Small” Pharma

- “Small” Pharma is more engaged
- Financial return better matched to size
- Market opportunity is more clear
- Regulatory uncertainty: a lesser concern?
- Focus
- For some, in-licensed compounds only
- Others, robust Discovery efforts
-          Will it be enough?

- 13 Apr 04

## What Has AATF Learned?Issues for VCs

- Access to venture capital is – of course - essential for new companies
- In a totally unscientific sampling:
- Some VCs see the dearth of discovery efforts as an opportunity
- Others consider the risks high because of restrictions on use of marketed products
- Late-stage anti-infective products are drivers of some financing decisions

- 13 Apr 04

## What has AATF Learned?Issues for FDA

- FDA understands the problem
- Wishes to partner in finding solutions
- Regulatory uncertainty, when present, further clouds the development process 				(FDA’s  2004 “Critical Path” report)
- Maintaining scientific rigor
- Limited flexibility per statutory constraints
- e.g., waiver of user fees not possible

- 13 Apr 04

## What has AATF Learned? Issues for CDC, NIAID, HHS

- Substantial, relevant efforts proposed
- PHS Action Plan to Combat Resistance (2001)
- NIH Roadmap for Medical Research (2003)
- More funding needed for critical efforts
- More could be done to foster inter-agency collaboration, training, and outreach regarding antibacterial drug development

- 13 Apr 04

## What has AATF Learned? Issues for the Scientific and Lay Press

- Pipeline concerns -- of interest to both the scientific community and the public
- Articles directed to a wide readership
- Our communications must highlight not only measures to decrease resistance, but also those to ensure the pipeline

- 13 Apr 04

## “Bad Bugs, No Drugs” in the Scientific and Lay Press

- Lay Press
- Boston Globe, *"Firms Abandoning Antibiotics Research; Drugs That Make More Money Sought"* 				Christopher Rowland, Mar 13, 2004
- USA Today, *"Scientists: Research Cuts are Troubling"*
- 		Anita Manning, Sept 15, 2003
- Washington Post, *"Tougher Bugs, Few New Drugs"* 		Roxanne Nelson, Mar 30, 2004

- 13 Apr 04

## “Bad Bugs, No Drugs” in the Scientific and Lay Press

- General Scientific Readership
- Nature, *"Drug Companies Snub Antibiotics"* 			Tom Clarke, Sept 18, 2003
- Science, *"Orphan Drugs of the Future?"* 				Robert Service, March 19, 2004, pg 1798
- The Lancet, *"Antibiotic Development Pipeline Runs Dry"* 	Roxanne Nelson, Nov 22, 2003

- 13 Apr 04

## “Bad Bugs, No Drugs” in the Scientific and Lay Press

- ID Specialty Journals
- The Lancet Infectious Diseases, *"Covering the Parts Other Bioshields Don't Reach"*			 				editorial, Jan 2004
- The Lancet Infectious Diseases, *"Incentives to Lure Drug Companies to Antimicrobials"* 						Marilynn Larkin, Jan 2004
- Clinical Infectious Diseases, *“Trends in Antimicrobial Drug Development: Implications for the Future"* 				Spellberg et al, in press 2004

- 13 Apr 04

## What has AATF Learned? Issues for Congress

- Some vocal & effective supporters for addressing the issues, but
- Focus of policy-makers is elsewhere
- Bioterrorism
- Everything else...
- BioShield I offers some hope of solutions, but has substantial constraints
- More attention & action are needed

- 13 Apr 04

## What is IDSA’s Role in Defining Solutions?

- Raise awareness of the the problem
- Multiple venues
- Always speak to the needs of patients
- Brainstorm on possible solutions
- Many are not within IDSA’s area of expertise
- Partners needed
- IDSA can act as a catalyst

- 13 Apr 04

## Raising Awareness

- Visit with Dr. McClellan, senior FDA staff
- Visits with senior pharma executives
- Interactions with CDC, NIAID
- Legislative contacts
- Outreach to scientific and lay press
- “White Paper”, to be released in May

- 13 Apr 04

## Potential SolutionsPartnering of Stakeholders

- IDSA, FDA, CDC, NIAID, Pharma, & Congress in the interest of public health
- IDSA hopes that it can continue to play an important, constructive role in partnering efforts

- 13 Apr 04

## Potential SolutionsChanges in the Marketplace

- Greater marketplace receptivity to new antibacterials could alter economic equation
- But, potential changes are constrained
- Cost, concern re promotion of resistance
- Desire to hold antibiotics of last resort
-           Change unlikely, without scientific data to justify different usage patterns

- 13 Apr 04

## Potential SolutionsRegulatory adjustments

- Publish updated guidelines (on-going)
- Periodic, timely review and revision
- Encourage novel clinical trial designs to gather information on drug efficacy against resistant pathogens
- Define surrogate endpoints, PK/PD parameters, & preclinical data that could reduce # of clinical studies

- 13 Apr 04

## Potential SolutionsInitiatives by NIAID

- Responsible for implementing “Roadmap” for translational research
- Foster antimicrobial R&D
- Collaborative planning with industry, academia
- Fellowship curriculum in AI clinical trials
- NIAID-FDA programs to streamline development
- Fund research into rapid diagnostics
- Fund placebo-controlled trials in AECB, AS

- 13 Apr 04

## Potential SolutionsLegislative

- Ongoing
- The Project Bioshield Act
- Best Pharmaceuticals for Children Act
- Senators Gregg and Reed: GAO study
- Future
- S.666 (Lieberman and Hatch)
- Unique problems require unique solutions

- 13 Apr 04

## Potential SolutionsLegislative

- For investments in *priority antibacterials*
- Incentives successful elsewhere to spur R&D
- e.g.,  R& D tax credits
- Supplemental IP protections
-  e.g., wild card patent exclusivity
- Mechanisms to attract smaller companies
- e.g., waiver of user fees for supplemental NDAs

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## Potential SolutionsLegislative

- Commission on Antimicrobial Resistance (COAR)
- Broad representation from stakeholders
- Charges
- Identify priority pathogens
- Decide which antibiotics should receive the benefits of legislated incentives

- 13 Apr 04

## Potential SolutionsLegislative

- Increase Funding for Essential Programs
- CDC antimicrobial resistance program
- NIAID antimicrobial resistance research
- FDA programs re review/approval of antibacterials

- 13 Apr 04

## Potential SolutionsCorporate

- Industry can point with pride to many *pro bono* initiatives for human health
- GSK: Malaria effort with the MVI
- Merck: Ivermectin effort with WHO
- AZ: TB discovery effort, Bangalore
- Many others
- If this impending crisis explodes, the public will need your help

- 13 Apr 04

## Potential Solutions

- These considerations to be discussed in detail in IDSA’s White Paper, to be released in May

- 13 Apr 04

## Conclusions

- There is a problem
- Etiology is multifactorial
- No single, “easy” solution
- Essential partners *are* engaged
- Potential solutions apparent
- IDSA stands ready to make a long-term, constructive commitment to help address this brewing public health crisis

- 13 Apr 04

## Conclusions

- Bad Bugs, No Drugs....
- How Can IDSA Help?
*We Want Your Input*

- 13 Apr 04

## Final Notes

- Potential Conflicts
- No external financial support for AATF effort
- Some AATF members provide consultative services to industry
- Acknowledgements
- AATF members
- Factual input from J. Powers & D. Ross
- IDSA staff, esp. R. Guidos & D. Olson
- The many people with whom we have spoken

- 13 Apr 04