13 Apr 041 FDA – IDSA - ISAP Workshop April 15, 2004 Continuing Discussion on Incentives George H. Talbot MD On Behalf of the AATF

13 Apr 04 1

FDA – IDSA - ISAP WorkshopFDA – IDSA - ISAP WorkshopApril 15, 2004April 15, 2004

Continuing Discussion on Incentives

George H. Talbot MD

On Behalf of the AATF

13 Apr 04 2

Presentation ObjectivesPresentation 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 3

What has AATF Learned?What has AATF Learned?OverviewOverview

There is a problem– Complex, multifactorial etiology – Susceptible to oversimplification: “If only….”

No easy, single solutionPotential approaches are apparentProgress requires

– Long-term commitment– Active collaboration of essential partners

13 Apr 04 4

The ProblemThe 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 5

The ProblemThe ProblemTotal Approved Antibacterials: USTotal Approved Antibacterials: US

0

2

4

6

8

10

12

14

16

1983-1987

1988-1992

1993-1997

1998-2002

2003

Total # NewAntibacterial Agents

Spellberg et al, CID 2004 in press

13 Apr 04 6

What has AATF Learned?What has AATF Learned?Interactions with StakeholdersInteractions with Stakeholders

Pharmaceutical companiesVCsFDACDC, NIAID, HHSThe scientific and lay pressCongress

13 Apr 04 7

What Has AATF Learned?What Has AATF Learned? Issues for PharmaIssues 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 8

What Has AATF Learned?What Has AATF Learned? Issues for “Big” PharmaIssues 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 9

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

Any further uncertainty is a disincentiveFurther IP protections - ? upsideTax credits – interestingBecause of enormous hurdles for Discovery

infrastructure, we must keep those companies that are “In” – “In”

13 Apr 04 10

What Has AATF Learned?What Has AATF Learned?Issues for “Small” PharmaIssues 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 11

What Has AATF Learned?What Has AATF Learned?Issues for VCsIssues 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 12

What has AATF Learned?What has AATF Learned?Issues for FDAIssues 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 13

What has AATF Learned?What has AATF Learned? Issues forIssues for CDC, NIAID, HHSCDC, 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 14

What has AATF Learned?What has AATF Learned? Issues for the Scientific and Lay PressIssues 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 15

““Bad Bugs, No Drugs”Bad Bugs, No Drugs” in thein the Scientific and Lay PressScientific 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 16


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 17


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 18

What has AATF Learned?What has AATF Learned? Issues for CongressIssues 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 19

What is IDSA’s Role in What is IDSA’s Role in Defining Solutions?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 20

Raising AwarenessRaising Awareness

Visit with Dr. McClellan, senior FDA staffVisits with senior pharma executivesInteractions with CDC, NIAIDLegislative contactsOutreach to scientific and lay press“White Paper”, to be released in May

13 Apr 04 21

PotentialPotential Solutions SolutionsPartnering of StakeholdersPartnering 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 22

PotentialPotential Solutions SolutionsChanges in the MarketplaceChanges 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 23

PotentialPotential Solutions SolutionsRegulatory adjustmentsRegulatory 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 24

PotentialPotential Solutions SolutionsInitiatives by NIAIDInitiatives 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 25

PotentialPotential Solutions SolutionsLegislativeLegislative

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 26


For investments in priority antibacterialsIncentives 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

13 Apr 04 27


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 28


Increase Funding for Essential Programs

CDC antimicrobial resistance programNIAID antimicrobial resistance researchFDA programs re review/approval of

antibacterials

13 Apr 04 29

PotentialPotential Solutions SolutionsCorporateCorporate

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 30

PotentialPotential Solutions Solutions

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

13 Apr 04 31

ConclusionsConclusionsThere is a problemEtiology is multifactorialNo single, “easy” solutionEssential partners are engagedPotential solutions apparentIDSA stands ready to make a long-term,

constructive commitment to help address this brewing public health crisis

13 Apr 04 32

ConclusionsConclusions

Bad Bugs, No Drugs….

How Can IDSA Help?

We Want Your Input

13 Apr 04 33

Final NotesFinal NotesPotential Conflicts

– No external financial support for AATF effort– Some AATF members provide consultative

services to industryAcknowledgements

– AATF members– Factual input from J. Powers & D. Ross– IDSA staff, esp. R. Guidos & D. Olson– The many people with whom we have spoken

Documents

13 Apr 041 FDA – IDSA - ISAP Workshop April 15, 2004 Continuing Discussion on Incentives George H. Talbot MD On Behalf of the AATF