Hepatitis C: Perspective on Drug Development Issues

1
Hepatitis C Perspective onDrug Development
Issues

• Debra Birnkrant, M.D.
• Director, Division of Antiviral Products
• FDA
• Antiviral Drugs Advisory Committee
• October 19 and 20, 2006

2
Hepatitis C InfectionUnited States 1998-2003

• New infections (cases)/year 25 - 40,000
• Persons ever infected 4 million
• Persons with chronic infection 3 million
• Most common indication for liver transplantation
• Deaths /year 10,000
• 170 million chronically infected worldwide

3
Hepatitis C InfectionTherapy

• Five interferon alpha products approved alone or
  in combination with ribavirin
• Pegylated interferon with ribavirin SOC
• Limited efficacy in certain subgroups
• Tolerability issues
• Cost

4
Other
Antisense oligonucleotides
TLR agonists
Polymerase Inhibitors
Protease Inhibitors
Cyclosporine A analogs
Interferons
5
Meeting Scope

• Solicited information from HCV IND sponsors on
  clinical trial design issues
• Patient populations
• Controls for phase 3 studies
• Clinical trial designs
• Endpoint(s) to evaluate efficacy
• Long-term follow-up of patients

6
Patient Population(s)at the Time of Initial
Approval

• Naïve or experienced
• Compensated or decompensated
• Genotype
• Co-infection
• Liver transplantation
• Pediatrics
• Racial or ethnic subgroups

7
Control Groups

• Placebo controls
• SOC control
• Deferred therapy vs immediate therapy
• Need to consider patient population

8
Clinical Trial Designs

• Adding investigational agent to SOC
• Lower dose /- shorter duration of PEG-IFN plus
  investigational agent
• Ribavirin substitution
• Use of 2 or more investigational agents
• Monotherapy

9
Endpoints

• Histologic, virologic and biochemical
• Timing
• SVR12
• SVR24
• Patient population dependent

10
Agenda

• Epidemiology, natural history and viral
  kinetics
• Trial design difficulties
• Community perspective
• FDA summary of industry responses
• Questions and discussion