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					    Social Media

 ―The use of web-based
 technology to facilitate
interaction with others.‖
               ARS Question:
 With the exception of e-mail, how often do
you interact with peers online through social
 networking sites like Facebook & Twitter?
1)   Always
2)   Very Often
3)   Sometimes
4)   Rarely
5)   Never
              ARS Question:
      How likely are you to use social
       media to help increase public
     awareness of chronic hepatitis C?
1)   Very likely
2)   Likely
3)   Maybe
4)   Probably not
5)   Never
                 ARS Question:
     In patients who present with non liver
     related complaints, how often do you
       evaluate a patient’s risk factors for
         chronic hepatitis C infection?
1)   Always
2)   Very Often
3)   Sometimes
4)   Rarely
5)   Never
                 ARS Question:
 Among all your genotype 1 patients who are
eligible for current therapy, how often are you
 withholding therapy while waiting for novel
                     drugs?
 1)   Always
 2)   Very Often
 3)   Sometimes
 4)   Rarely
 5)   Never
               ARS Question:
   Among your genotype 1 patients, how
 frequently will you be incorporating novel
      agents once they are approved?

1)   Always
2)   Very Often
3)   Sometimes
4)   Rarely
5)   Never
       How Will Social Media
       Impact Your Practice?

      Bryan S. Vartabedian, MD, FAAP
          Assistant Professor of Pediatrics
Section of Gastroenterology, Hepatology, & Nutrition
            Baylor College of Medicine
                  Houston, Texas
  How Health Information Was Shared



                    MD



                                             Patient

Graphic courtesy of Dr. Bryan Vartabedian.
             Evolution of Social Health

                                        Now
                              Patients find each other
                                      2000s
                            Information finds patients

                                       1990s
                             Patients find information

                                Long ago
                   Patients depend on what they’re told


Graphic courtesy of Dr. Bryan Vartabedian.
                                            4: Individuals – email lists
                                            3: Closed networks – MySpace, Facebook
                                            2: Open networks – blogs, feeds, YouTube
                                            1: Mainstream media – press, influencers




Armano D. Influence ripples. Available at: http://darmano.typepad.com. Accessed on: April 13, 2010.
“You don‟t need to go any
 further doctor. Just spell
„eosinophil‟ if you would.”
                                   CureTogether




Available at: http://www.curetogether.com. Accessed on: April 13, 2010.
                                   CureTogether

 • Patient to patient
 • Crowdsourced data
 • ―Clinical trials‖




Available at: http://www.curetogether.com/Irritable-Bowel-Syndrome/treatments/.
Accessed on: April 13, 2010.
      Participatory Medicine

• User-generated healthcare is shifting the
  balance of power from doctor to patient

• The physician encounter is evolving
  as a narrow, more defined element in a
  patient’s quest to understand what’s
  wrong with them
       What Is Social Media?

• Content created by people using scalable
  online publishing technologies intended to
  facilitate communication and interaction

• Most often refers to activities that integrate
  technology, telecommunications, and social
  interaction, with the construction of words,
  pictures, videos, and audio
With permission from Solis B, et al. The conversation prism. Available at: http://www.theconversationprism.com.
Accessed on: April 13, 2010.
   Percentage of Adults Who Look Online
           for Health Information




                                                                 61%




Fox S. The social life of health information. January 14, 2009. Pew Internet & American Life Project.
Available at: http://pewinternet.org/~/media//Files/Reports/2009/PIP_Health_2009.pdf. Accessed on:
April 13, 2010.
              The Social Media Revolution
           How Is Its Use in Adults Growing?




                                     2005                        2009

Lenhart A. Adult and Social Network Websites. January 14, 2009. Pew Internet & American Life Project.
Available at: http://pewinternet.org/Reports/2009/Adults-and-Social-Network-Websites.aspx. Accessed on:
April 13, 2010.
    US Hospitals on YouTube and Twitter




With permission from Bennett E. Hospital social network data and charts. Available at:
http://ebennett.org/hsnl/data/. Accessed on: April 13, 2010.
      Where Are the Doctors?
The Absence of MDs in Social Media Space

• Late adopters
• Time/impatience
• Concerns over privacy, liability, and image
     What Can You Do on
      Social Networks?

• Educate patients
• Influence behavior
• Promote awareness of yourself or
  your hospital
• Build relationships
• Filter information
Armano D. Human feed. Available at: http://darmano.typepad.com. Accessed on: April 13, 2010.
                                                         Do Physicians
                                                             Have an
                                                        Obligation To Be
                                                          in the Online
                                                             Space?



                                                                  60,000
                                                          Number of Pediatricians
                                                               in the AAP
KevinMD.com. Available at: http://www.kevinmd.com/blog/2009/08/delayed-vaccine-schedule-
dangerous.html. Accessed on: April 13, 2010.
        DDW’s 4 Sponsoring Societies

              16,000                                             3000
         Number of Members                               Number of Members
            in the AGA                                     in the AASLD


              10,000                                             2500
         Number of Members                               Number of Members
            in the ASGE                                     in the SSAT
Abbreviations: AASLD, American Society for the Study of Liver Diseases; AGA, American
Gastroenterological Association; ASGE, American Society for Gastrointestinal Endoscopy; DDW, Digestive
Disease Week; SSAT, The Society for Surgery of the Alimentary Tract.
DDW 2010. FAQs. Available at: http://www.ddw.org/wmspage.cfm?parm1=710.
Accessed on: April 13, 2010.
How Should Physicians Handle
  Patient Encounters in the
    Social Media Space?



        They Shouldn’t
Staying Safe on Social Networks


• Never discuss patients
• Patients, boss, future employer
  will read everything you write
• Be nice
• Don’t be anonymous
                                             Blog




                    Put a stake in the ground
Graphic courtesy of Dr. Bryan Vartabedian.
                                             Blog




Graphic courtesy of Dr. Bryan Vartabedian.
                                                                                Visibility in Action




Left graphic: Kaplan Publishing. Spring 2009 Catalog. Available at: http://www.kaptest.com/pdf_files/publishing/seasonal-
catalogs/KPSpring09Catalog.pdf. Accessed on: April 13, 2010. Upper right graphic: Courtesy of Dr. Bryan Vartabedian. 33 Charts
blog. Available at: http://www.33charts.com. Lower graphic: Courtesy of Dr. Bryan Vartabedian. Personal Correspondence. 2010.
Armano D. Conversion. Available at: http://darmano.typepad.com. Accessed on: April 13, 2010.
   The Low Rates of Chronic HCV
     Diagnosis and Treatment:
    Why and What Can We Do?


      Hashem B. El-Serag, MD, MPH
               Professor of Medicine
Chief, Section of Gastroenterology and Hepatology
            Baylor College of Medicine
      Michael E. DeBakey VA Medical Center
                  Houston, Texas
               Past and Future US Incidence
              and Prevalence of HCV Infection
                                                 Decline among IDUs



                                                                   Overall incidence




                                                                   Overall prevalence


                                                            Infected 20+ years



Armstrong GL, et al. Hepatology. 2000;31:777-782. Graphic courtesy of the CDC.
                     Histologic Fibrosis Stage by Year
 Number of Persons




                                                   Year
Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings L . Gastroenterology 2010
Slide Not
Available
    Hepatitis C—Age-Adjusted Rates of Ambulatory Care
       Visits and Hospital Discharges with All-Listed
        Diagnoses in the United States, 1979–2004




Data from National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey
(NHAMCS) (averages 1992-1993, 1994-1996, 1997-1999, 2000-2002, 2003-2005), and National Hospital Discharge
Survey (NHDS).
Everhart JE, ed. The burden of digestive diseases in the United States. 2008. NIDDK: US Government Printing Office,
2008; NIH Publication No. 09-6443.
     Efficacy of Peginterferon + Ribavirin in
  Achieving Sustained Virologic Response (SVR)

             Category                                          SVR (%)
             Overall                                            54–561,2
             Genotype 1                                         42–461,2
             Genotype 2/3                                       76–821,2
             Genotype 4                                        58–772–4
             African American                                       285
             Cirrhosis                                          43–441,2

1. Manns M, et al. Lancet. 2001;358:958-965. 2. Fried M, et al. N Engl J Med. 2002;347:975-982.
3. Kamal SM, et al. Hepatology. 2007;46:1732-1740. 4. Khuroo MS, et al. Aliment Pharmacol Ther.
2004;20:931-938. 5. Conjeevaram H, et al. Gastroenterology. 2006;131:470-477.
HCV Patients Most Likely to Achieve SVR

      Virus Factors                         Treatment Factors
Genotype 2/3                            Tolerability
Low viral load                          Adherence
Rapid virologic response                Provider experience
                                        Supportive medical team



                          Host Factors
                 IL28B gene polymorphism
                 Not African American
                 Immunocompetent
                 Lean, non-diabetic, insulin sensitive
                 Young, good renal function, minimal
                 comorbid illness
                         Treatment of HCV


          Efficacy in                                Effectiveness in
      clinical trials and                              community
      research centers                                   practice




                                                  Efficacy x Access x
                                                  Correct Diagnosis x
                                                  Recommendation x
                                                Acceptance x Adherence
El-Serag HB. Gastroenterology. 2007;132:8-10.
                     Efficacy and Effectiveness
                  A Demonstration of the Multiplicative
                          Effect of Factors
        Example 1:                        Example 2:              Example 3:
          Rx ―X‖                            Rx ―Y‖              Rx ―X‖ Modified
  Efficacy of Rx        60%         Efficacy of Rx   80%     Efficacy of Rx   60%
  ―X‖                               ―Y‖                      ―X‖
  Access               x 80%        Access           x 80%   Access           x 90%

  Correct              x 85%        Correct          x 85%   Correct          x 90%
  diagnosis                         diagnosis                diagnosis
  Recommend            x 85%        Recommend        x 85%   Recommend        x 90%
  Acceptance           x 85%        Acceptance       x 85%   Acceptance       x 90%

  Adherence            x 70%        Adherence        x 70%   Adherence        x 80%

  Effectiveness        = 21%        Effectiveness    = 28%   Effectiveness    = 32%
  of Rx ―X‖                         of Rx ―Y‖                of Rx ―X‖
                                                             modified
El-Serag HB. Gastroenterology. 2007;132:8-10.
      Awareness of HCV Infection Among
            HCV-Infected Persons




Colvin HM, Mitchell AE, eds. Hepatitis and liver cancer: a national strategy for prevention and control of
hepatitis B and C. Institute of Medicine. Washington, DC: The National Academies Press, 2009.
                  Predictors of Treatment
         Patient                                          Provider
         factors                                           factors

                                                        Provider specialty
       Demographics
                                                        HCV experience
 Genotype, viral load
                                                        Continuity
  Cirrhosis diagnosis                      Receipt of
ALT, Hct, Plt, WBC, Cr                     Treatment
          Comorbidity
        HIV diagnosis
             Insurance



                                            Facility
                                            factors
Graphic courtesy of Dr. Hashem El-Serag.
             Eligibility and Acceptability of
                      HCV Treatment
•    4084 HCV+ patients in VA Multicenter Study 12/99–12/00
•    Eligibility – 32% by standard criteria, 41% by treating physician
      –     Predictors of noneligibility
                 Ongoing substance abuse                OR 17.68
                 Comorbid medical disease               OR 9.62
                 Psychiatric disease                    OR 9.45
                 Advanced liver disease                 OR 8.43

•    Acceptability – 76% of eligible patients
      –     Reasons for nonacceptance
                 Defer Rx until better therapies        50%
                 Concerns regarding side effects        22%

•    Treatment completion rates
      –     ~50% of those treated (~8% of all patients)

Bini E, et al. Am J Gastroenterol. 2005;100:1772-1779.
                      Treatment Outcomes
               Retrospective Observational Cohort
                                                                   Completed treatment
                                                                   Achieved SVR
                     N = 5944




48-week treatment for genotype 1, 24-week treatment for genotype 2/3.

Backus LI, et al. Hepatology. 2007;46:37-47.
       Antiviral Therapy for HCV per Year
                            Actual, 2002–2007
                         Projected, Through 2014

                                                 Actual
                                                 Projected




Volk ML, et al. Hepatology. 2009;50:1750-1755.
            Underutilization and Disparity

                                           Clinical appropriateness
                                           and patient preferences

                                             Healthcare system:
                                             access, legal, and        Under-
Percent




                                              regulatory issues       utilization
                                                                         and
                                            Discrimination, bias,     Disparity
                                                uncertainty




Graphic courtesy of Dr. Hashem El-Serag.
       Reasons for Lack of Treatment Among
      Respondents to the NHANES Hepatitis C
            Follow-Up Questionnaire
                                                                         N = 133
      Survey Responses




                                                        Refused treatment

                                                        Did not f/u with clinician
                                                        Received treatment
                                                        Clinician did not recommend treatment
                                                        Unaware of diagnosis




Abbreviation: NHANES, National Health and Nutrition Evaluation Survey.
Volk ML, et al. Hepatology. 2009;50:1750-1755.
                           Summary
•   HCV prevalence peaked in 2001 at 3.6 million persons
•   Number and proportion of HCV patients with cirrhosis,
    decompensation, and HCC will increase for at least
    another 10–15 years
•   Age of persons with complications will rise
•   Will antiviral therapy change the future?
    –   Eradication of HCV stops progression, eliminates the risk of
        liver failure, and reduces HCC risk
           Requires therapeutic intervention before onset of advanced
            fibrosis
           Requires identification of infected cases
                     Summary

•   Clinical effectiveness is dependent on
    several factors in addition to clinical efficacy
    – HCV diagnosis
    – Referral to specialists
    – Treatment of comorbidities
    – Adherence to treatment
                 Institute of Medicine Report
                                  Underlying Factors

• Lack of knowledge and awareness about
  chronic viral hepatitis among

        Healthcare and                                                          Policy makers
        social service                   At-risk populations                         and
          providers                                                               the public



• Insufficient understanding about the extent
  and seriousness of this public health problem

Colvin HM, Mitchell AE, eds. Hepatitis and liver cancer: a national strategy for prevention and control of
hepatitis B and C. Institute of Medicine. Washington, DC: The National Academies Press, 2009.
                    Institute of Medicine Report
                                            Consequences
                      Inadequate                                      People with chronic
                 surveillance systems                                 HCV infection do not
                 underreport acute and                                  know they are
                   chronic infections                                       infected

  At-risk people do not                                                              Many clinicians do not
                                                                                      know how to screen
  know they are at risk
                                                                                    people for risk factors or
  or how to avoid being                                                              manage those who are
         infected                                                                           infected

                                                                       HCV-infected people
                    At-risk people may
                                                                      often have inadequate
                    not have access to                               access to testing, social
                    preventive services                               support, and medical
                                                                      management services

Colvin HM, Mitchell AE, eds. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C.
Institute of Medicine. Washington, DC: The National Academies Press, 2009.
                    Institute of Medicine Report
                                       Recommendations
                                                 Knowledge &                             Viral Hepatitis
        Surveillance
                                                  Awareness                                 Services
   The CDC should:                          The CDC should work                       Federally funded
                                            with key stakeholders                     health insurance
   Evaluate national
                                            to:                                       programs (eg,
   HCV public health
                                                                                      Medicare) should:
   surveillance system                      Develop HCV
   Develop agreements                      educational programs                      Incorporate
   with state health                        for providers                             guidelines for risk-
   departments to                           Develop and                              factor screening as
   support core HCV                         evaluate innovative                       required component of
   surveillance                             and effective outreach                    preventive care
   Support targeted                        programs to 1) target
   surveillance                             at-risk populations,
                                            and 2) increase public
                                            awareness

Colvin HM, Mitchell AE, eds. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C.
Institute of Medicine. Washington, DC: The National Academies Press, 2009.
              ARS Question:
      How likely are you to use social
       media to help increase public
     awareness of chronic hepatitis C?
1)   Very likely
2)   Likely
3)   Maybe
4)   Probably not
5)   Never
                 ARS Question:
     In patients who present with non liver
     related complaints, how often do you
       evaluate a patient’s risk factors for
         chronic hepatitis C infection?
1)   Always
2)   Very Often
3)   Sometimes
4)   Rarely
5)   Never
Optimization of Interferon-
   Based Therapies in
 Current HCV Patients–
   Can We Do Better?

     Donald M. Jensen, MD
        Professor of Medicine
  Director, Center for Liver Diseases
 University of Chicago Medical Center
            Chicago, Illinois
              Why Do Current Drugs Fail?
• Viral factors1
        – Viral protein products as inhibitors of innate
          immunity
        – Viral proteins as inhibitors of adaptive responses
• Host factors
        – Fixed: race, genetics, age, gender
        – Modifiable: body mass index, insulin resistance,
          steatosis1
• Treatment factors
        – Dose, duration, adherence, tolerability
1. Tai AW, et al. J Hepatol. 2009;50:412-420.
                         Baseline Predictors
• Host genetic makeup
      – IL28B polymorphism1
                 Allele on chromosome 19, rs12979860
                 Resides 3 kilobases upstream from the IL28B gene
                  encoding IFN-gamma-3
                 Strongly associated with rate of sustained virologic
                  response
      – Other racial and genetic factors
• Viral factors
      – Genotype
      – Viral load
1. Ge D, et al. Nature. 2009;461:399-401.
 Importance of IL28B Polymorphisms

• C/C genotype is more common in racial
  groups with a higher sustained virologic
  response (SVR)
• C/C genotype is associated with a higher SVR
  compared with T/C or T/T
• IL28B polymorphisms may partially explain
  racial differences in antiviral response and
  may be a useful pretherapy tool


Ge D, et al. Nature. 2009;461:399-401.
         C Allele is Associated with SVR
       Percentage SVR by Genotype of rs12979860
                 n = 186
                 n = 70                                  Combined
         T/T     n = 14                                  African Americans
                 n = 102
                                                         Hispanics
                                                         European Americans
                 n = 559
                 n = 91
        T/C      n = 35                                  N = 1,137
                 n = 433


                 n = 392
                 n = 30
        C/C      n = 26
                 n = 336                                       P = 1.37 x 10-28 vs T/T


                0           20           40         60       80        100
                                              SVR
Ge D, et al. Nature. 2009;461:399-401.
                                        IL28B Genetic Variation and
        rs12979860 C-allele Frequency      Genotype 1 Response

                                                        European Americans   East Asians
                                                             (n = 271)        (n = 107)

                                                               Hispanics
                                                                (n = 16)

                                           African Americans
                                                 (n = 61)




                                                                  SVR (%)

Ge D, et al. Nature. 2009;461:399-401.
                                    Treatment of Chronic HCV
                                               Genotype 1 Response Rate
                          10
    Log HCV RNA (IU/mL)




                           9
                                                          PEG IFN + RBV THERAPY                                SVR
                          8
                                                   1   Stopping        2
                          7
                                                        Rules
                          6                                                                                    2%–5%
                          5                                     Null
                                                                                 ~29%
                          4                                                                                  27%–43%
                                                                Partial
                          3
                          2                                 pEVR                                             68%–72%
                                        RVR        cEVR
                          1             ~20%
                                                                                                             88%–91%
                          0                           51%
                               -6   0    4     8    12 16     20   24      28   32   36   40   44    48   72

                                                               Weeks                           Detection limit (50 IU/mL)
Abbreviations: EVR, early virologic response; cEVR, complete EVR; pEVR, partial EVR; RVR, rapid virologic response.
1. Jensen DM, et al. Hepatology. 2006;43:954-960. 2. Ghany MG, et al. Hepatology. 2009;49:1335-1374. 3. Fried MW, et al.
N Engl J Med. 2002;347:975-982. 4. Manns MP, et al. Lancet. 2001;358:958-965. 5. Davis GL, et al. Hepatology.
2003;38:645-652. Graphic courtesy of Dr. Donald Jensen.
                Improving Current Therapy
                                             2 Goals
• Increase SVR rate
       – Decrease risk of hepatocellular carcinoma (HCC)1,2
       – Decrease risk of decompensation3,4
       – Improve fibrosis/reversal of cirrhosis4
       – Improve quality of life5
• Improve adherence and tolerability
       – Shorten treatment duration if RVR
       – Minimize treatment-related adverse events

1. Craxi A, et al. Clin Liver Dis. 2005;9:329-346. 2. Shiratori Y, et al. Ann Intern Med. 2005;142:105-114.
3. Shiratori Y, et al. Ann Intern Med. 2000;132:517-524. 4. Poynard T, et al. Gastroenterology.
2002;122:1303-1313. 5. Foster GR, et al. J Viral Hepat. 2009;16:605-611.
     Goal—Increase SVR Rate

Current options
• Increase interferon and/or ribavirin dose
• Increase adherence
• Increase treatment duration


   Is there evidence that these work?
                        Induction Dosing of Interferon
                       Induction IFN dosing         Proportions of Patients with Undetectable
                         leads to a greater        HCV RNA After Starting Combination Therapy1
                          number of early
                            responders.
                        However, standard
                      dosing catches up after
                          induction ends.
HCV RNA neg (%)




                      Induction IFN


                                      Std IFN
                                                          There is no overall
                                                             SVR benefit to
                                                           induction dosing
                  0        24
                          12        36        48
                          Weeks
Abbreviations: CR, conventional; HR, high-dose induction. 1. Upper right graphic with permission from Kim
TH, et al. Intervirology. 2005;48:230-238. Lower left graphic courtesy of Dr. Donald M. Jensen.
       Evidence for Increased RBV Dosing
 PEG IFN -2b/RBV Registration Trial1
            All genotypes

     100
      80
                                                                      WIN-R Trial2
                                                                      Genotype 1
      60                              P = .015
      40                                                                               Weight-baseda
                                                                                       Flat-dosingb
      20

       0
           5      9      13      17      21
                RBV Dose (mg/kg)




aP = .569; bP = .019.
1. Manns MP, et al. Lancet. 2001;358:958-965. 2. Jacobson IM, et al. Hepatology. 2007;46:971-981.
                        Importance of RBV Adherence
      Effect of RBV Exposure on Relapse Rate1                   Adherence messages
                   80                    Cumulative Ribavirin     • Maintain RBV dose
                                         Dose                       >60% over entire
                   70                       >97% (n = 37)           treatment1,2
Relapse Rate (%)




                                            80%–97% (n = 14)
                   60                                             • Use 200 mg dose
                                            60%–80% (n = 18)
                   50
                                                                    reduction steps1,2
                                            0%–60% (n = 13)
                                                                  • For anemia, use
                   40
                                                                    erythropoiesis-
                   30                                               stimulating agents
                                                                    sparingly (black box
                   20                                               warning)3-5
                   10
                         19   22 32 54
                    0


1. Reddy KR, et al. J Hepatol. 2009;50:402-411. 2. Reau N, et al. Am J Gastroenterol. 2008;103:1981-
1988. 3. Sulkowski MS, et al. J Viral Hepat. 2004;11:243-250. 4. Afdhal NH, et al. Gastroenterology.
2004;126:1302-1311. 5. US FDA. News release. March 9, 2007.
                          Extending Duration
             Genotype 1 with Early Virologic Response
              0 4        12                          48               72
  Week                                                                       SVR             Relapse
              All patient analysis
Berg1                            48 weeks
G1 only
RBV 800 mg                       72 weeks                                   53    54         29    21

              HCV RNA pos at week 12; neg at week 24                         P = .04
Berg1
                                 48 weeks
G1 only                                                                                      64    40
RBV 800 mg                       72 weeks                                   17    29

                                                                             P = .03         P = .004
Pearlman2 HCV RNA pos at week 12; neg at week 24
G1                     48 weeks
RBV 800/                                                                           38         59
1400 mg                72 weeks                                             18                     20



1. Berg T, et al. Gastroenterology. 2006;130:1086-1097. 2. Pearlman BL, et al. Hepatology.
2007;46:1688-1694. Graphic courtesy of Dr. Donald M. Jensen.
 Can We Shorten Therapy
     Based on an RVR
to Improve Adherence and
  Minimize Side Effects?
             Utilizing RVR to Shorten Therapy in
                         Genotype 1
                               PEG IFN -2a/RBV2

                                           24 wk + RBV 800
                                                                      For genotype 1,
       100
                    89 88            91    24 wk + RBV 1000/1200     retrospective and
                                           48 wk + RBV 800
         80
                                73         48 wk + RBV 1000/1200
                                                                      prospective data
                                                                    suggest 24 weeks of
   SVR (%)




         60
                                                                      therapy may be
                                                          44
         40                                          35            adequate when RVR is
                                                23                 achieved (particularly
         20                               16
                                                                       those with low
                 n = 18   33   40    56    81   84   208 210
             0                                                      baseline HCV RNA)1-6
                    Patients with         Patients without
                   an RVR at wk 4         an RVR at wk 4

1. Zeuzem S, et al. J Hepatol. 2006;44:97-103. 2. Graphic with permission from Jensen DM, et al.
Hepatology. 2006;43:954-960. 3. Ferenci P, et al. Gastroenterology. 2008;135:451-458. 4. Yu ML, et al.
Hepatology. 2008;47:1884-1893. 5. Zeuzem S, et al. J Viral Hepat. 2009;16:75-90. 6. Nelson DR, et al.
Clin Gastroenterol Hepatol. 2009;7:397-414.
               Utilizing RVR to Shorten Therapy in
                        Genotypes 2 and 3
                       Accelerate Trial1
                 SVR Rates in Patients with RVR
                                        Any genotype
                  P = .02               Genotype 2                  For genotype 2 or 3,
     100                                Genotype 3
                                        85 85 85
                                                                     conflicting clinical
          80    79   78     80                                     trials data, but largest
SVR (%)




          60                                                       study to date suggests
                                                                     shortening therapy
          40
                                                                     may lead to greater
          20                                                            relapse rates1-7
          0
                16-wk Regimen          24-wk Regimen
   1. Shiffman ML, et al. N Engl J Med. 2007;357:124-134. 2. von Wagner M, et al. Gastroenterology.
   2005;129:522-527. 3. Mangia A, et al. N Engl J Med. 2005;352:2609-2617. 4. Lagging M, et al.
   Hepatology. 2008;47:1837-1845. 5. Dalgard O, et al. Hepatology. 2008;47:35-42. 6. Andriulli A, et al.
   Dig Liver Dis. 2006;38:741-748. 7. Nelson DR, et al. Clin Gastroenterol Hepatol. 2009;7:397-414.
    Response-Guided Therapy
             A New Paradigm?


Individualized treatment based on viral
kinetic measurements should….
• Improve overall cost-benefit
• Improve tolerability for those with RVR
• Decrease relapse rate
Nonresponders
                PEG IFN/RBV Nonresponder
                      Clinical Trials
                                              EPIC31
    476                  PEG IFN -2b 1.5 mcg/kg + RBV                              SVR:
    NRs                  800–1400 mg/d x 48 wk                                      6% overall
                                                                                    4% geno-1

                                            REPEAT2
   942                   PEG IFN -2a 180 or 360/180 g/wk + SVR:
   Geno-1 NRs            RBV 1000–1200 mg/d x 48 or 72 wk    7%–16%

                                            DIRECT3
    659                  cIFN 9 or 15 g/d + RBV 1000–1200                          SVR:
    Geno-1 NRs           x 48 weeks                                                 7%–11%

Abbreviation: cIFN, consensus interferon.
1. Poynard T, et al. Gastroenterology. 2009;136:1618-1628. 2. Jensen DM, et al. Ann Intern Med.
2009;150:528-540. 3. Bacon BR, et al. Hepatology. 2009;49:1838-1846.
Maintenance Therapy
      Maintenance PEG IFN in Nonresponders
                     3 Randomized Controlled Trials

                     HALT-C                COPILOT                Bruix, et al
                 No difference Subjects with  In primary
                  in clinical    baseline      analysis,
                  outcomes1        portal    maintenance
                               hypertension     was not
                               had reduced    superior to
                   Subgroup     outcomes     observational
                   with >4-log   (variceal     control in
                  reduction in   bleeding)    preventing
                 HCV RNA had with PEG IFN3 occurrence of
                    reduced                     clinical
                   outcomes  2
                                                events4


1. Di Bisceglie AM, et al. Hepatology. 2007;46:LB1. 2. Shiffman ML, et al. J Hepatol. 2008;48:S62.
3. Afdhal NH, et al. J Hepatol. 2008;48:S4. 4. Bruix J, et al. J Hepatol. 2009;50(suppl 1):S22.
        Treat Now or Wait Until STAT-C?
    Treat Now                   May Consider Waiting

•    Advanced fibrosis          •   Genotype 1 with mild
•    Symptomatic                    histology
•    Genotype 2, 3, or 4        •   PEG IFN/RBV prior
                                    nonresponders
•    IL28B C/C genotype (?)
                                •   IL28B T/T or T/C
                                    genotype



    Interferon and ribavirin will be required in combination
          with all new STAT-C agents for several years
                 Conclusions

• Response-guided therapy is important
  theme now for optimizing existing
  interferon/ribavirin-based therapies
• Improvements in current standard of care
  can be demonstrated by
   – Identifying likely responder populations
   – Shortening treatment duration in patients with
     RVR and poor tolerability
   – Extending treatment duration in patients with
     slow partial response
                 ARS Question:
 Among all your genotype 1 patients who are
eligible for current therapy, how often are you
 withholding therapy while waiting for novel
                     drugs?
 1)   Always
 2)   Very Often
 3)   Sometimes
 4)   Rarely
 5)   Never
       How Will STAT-C Therapies
         Affect Future Anti-HCV
         Treatment Paradigms?

               Ira M. Jacobson, MD
          Vincent Astor Professor of Medicine
  Chief, Division of Gastroenterology and Hepatology
Medical Director of the Center for the Study of Hepatitis C
       Weill Medical College of Cornell University
                  New York, New York
                      Phases in the Evolution
                       of Anti-HCV Therapy

                                 The                       The Phase
                                                                                         The
                             Refinement                          of
                                                                                         Final
      The                                                  Specifically
                               Phase                        Targeted
                                                                                        Phase:
     Empiric                • Optimal dosing
                                                             Antiviral
                                                                                        Small
     Phase                  • Viral kinetics                                           Molecule
                            • Challenging                    Therapy
                                                                                     Combinations
                              populations                    for HCV
                                                                                         ???
                            • Nonresponders                 (STAT-C)




Weisberg IW, et al. Current Hepatitis Reports. 2007;6:75-82. Graphic courtesy of Dr. Ira Jacobson.
             Emerging Anti-HCV Therapies
Specifically Targeted Antiviral Therapy for HCV
                  (STAT-C)
         Enzyme                       Genome
        Inhibitors                 Sequence-Based                             Other
                                                                   IFN and RBV modifications
                                           RNA                     • Albinterferon
        Protease                                                   • PEG IFN lambda (IL-29)
                                       Interference                • Other IFN formulations
                                                                   • Taribavirin (viramidine)

                                                                   Immune approaches
      Polymerase                        Antisense                  • Therapeutic vaccines
                                                                   • Toll-like receptor agonists
                                                                   • Hepatitis C immune
                                                                     globulin
                                                                   • Monoclonal antibodies
           NS5A
                                                                   Targeting cellular factors
                                                                   • Cyclophilin antagonists
Abbreviations: HCV, hepatitis C virus; IFN, interferon; PEG IFN,
                                                                   • Nitazoxanide
peginterferon; RBV, ribavirin.                                     • mIR-122 inhibitors
Graphic courtesy of Dr. Ira Jacobson.                              • Entry inhibitors
                   Hepatitis C Virus Life Cycle




With permission from Tellinghuisen TL, et al. J Virol. 2007;81:8853-8867.
                                   HCV Genome




With permission from Tellinghuisen TL, et al. J Virol. 2007;81:8853-8867.
               Targets for Anti-HCV Drugs in
               Beyond Phase I Clinical Trials

        Core   E1    E2   P   NS2         NS3   NS4A   NS4B     NS5A      NS5B
 5–                                                                                –3
                          7

                                                         NS5A             Polymerase
                    Protease inhibitors
                                                       inhibitors          inhibitors
                                Telaprevir             BMS-790052
                                Boceprevir
                                RG7227
                                TMC 435350             Active site      RG7128
                                MK7009                 (nucleosides)    IDX184
       Cyclophilin              BI-201335                               PSI-7851
       Antagonists              BMS-650032             Nonnucleosides   GS 9190
                                ABT-450                                 Filibuvir
                                                                        ABT-333
       Debio 025                                                        ABT-072
       SCY-635                                                          ANA598
                                                                        VX-222

Not all-inclusive
                            Early Data with Telaprevir
                   Potency, Resistance, and Interaction with IFN
HCV RNA Change from Baseline




                               1                                                            Sequence
                                                                                            Analysis
                               0                                                            Baseline
        (Log10 IU/mL)




                               -1                                                           PEG IFN -2a +
                                                                                            Placebo n = 4
                               -2               • More resistant variants emerged with TVR monotherapy
                                                • Patients went on to receive 24 wk PEG IFN + RBV
                               -3               • Resistant variants were suppressed by PEG IFN + RBV

                               -4                                                           Telaprevir n = 8

                               -5
                                                                                            Telaprevir +
                                                                                            PEG IFN -2a
                               -6
                                                                                            n=8
                                    1   2   3   4   5   6   7   8   9   10 11 12 13 14 15
                                                            Study Time (days)
Abbreviations: PEG IFN, peginterferon; RBV, ribavirin; TVR, telaprevir.
With permission from Kieffer TL, et al. Hepatology. 2007;46:631-639.
  PROVE1—Telaprevir Phase IIb Study Design
      US, Genotype 1, Treatment-Naive
        Weeks   0               12         24            36            48             60            72
       PR48
    (control)       Placebo +
                      P+R
                                                P+R                              Follow-up
     (n = 75)

  T12/PR12
                    T+P+R              Follow-up
    (n = 17)

  T12/PR24
             T+P+R                   P+R            Follow-up
    (n = 79)

  T12/PR48
             T+P+R                              P+R                              Follow-up
    (n = 79)

        Weeks 0                 12         24            36            48             60            72


Abbreviations: R, ribavirin 1000–1200 mg/d; P, peginterferon -2a 180 µg/wk; T, telaprevir 1250 on day 1
then 750 mg q8h.
McHutchison J, et al. N Engl J Med. 2009;360:1827-1838.
    PROVE 1—Telaprevir + PEG IFN/RBV
                      SVR, Intent-to-Treat Analysis, Phase II


                    100
     SVR Rate (%)




                    80
                                                                                67
                                                            61
                    60
                                                          P = .02            P = .002
                                  41
                    40                        35


                    20

                          n=     31/75       6/17         48/79               53/79
                     0
                               PR 48 wk    T 12 wk +   T 12 wk +           T 12 wk +
                               (Control)   PR 12 wk    PR 24 wk            PR 48 wk


Graphic Courtesy of Dr. John McHutchison. McHutchison JG, et al. N Engl J Med. 2009;360:1827-1838.
                                 PROVE 1—Relapse Rates

                       50
    Relapse Rate (%)




                       40
                                                33
                       30
                                   23                     TVR drives high rates of RVR
                                                            and low rates of relapse
                       20


                       10                                                        6
                                                               2
                            n=     8/35         3/9           1/41             3/51
                       0
                                 PR 48 wk    T 12 wk +     T 12 wk +        T 12 wk +
                                                      a              a
                                 (Control)   PR 12 wk      PR 24 wk         PR 48 wk



Denominator = number of subjects with undetectable HCV RNA at completion of assigned treatment duration.
aIncludes subjects who met the RVR criterion and stopped at 12 or 24 total weeks of treatment.

Graphic Courtesy of Dr. John McHutchison. McHutchison JG, et al. N Engl J Med. 2009;360:1827-1838.
    PROVE 1—Viral Breakthrough by Week 12
•     12/175 (7%) of telaprevir-treated patients had
      breakthrough
       –     9/12 occurred in first 4 weeks
       –     3/12 occurred between weeks 5 and 12
       –     Only 2 breakthroughs occurred in subjects after HCV RNA
             became undetectable
•     Telaprevir-resistant viral variants
       –     V36M and R155K (10 patients with genotype 1a)
       –     A156T (1 patient with genotype 1b)
       –     Wild type (1 patient who missed several days)




McHutchison JG, et al. N Engl J Med. 2009;360:1827-1838.
                       PROVE1—Safety Data




                                                                     Other TVR-related AEs:
                                                                       anemia, GI effects




Abbreviations: AE, adverse event; D/C, discontinuation; GI, gastrointestinal; TVR, telaprevir.
McHutchison JG, et al. N Engl J Med. 2009;360:1827-1838. Graphic courtesy of Dr. Ira Jacobson.
                                 PROVE2—SVR
       European, Genotype 1, Treatment-Naive
                                              Higher relapse rate
                                              with 12 vs 24 weeks

                                                                               Impaired response,
                                                                               more breakthrough
                                                                                and more relapse
                                                                                   w/out RBV




                    n = 38/82              49/82            56/81             28/78


                                                     a                b                c



aP = .004 vs control; bP = .12 vs control; cP = .003 vs control. Abbreviations: P, peginterferon -2a 180
µg/wk; R, ribavirin 1000–1200 mg/d; T, telaprevir 1250 mg on day 1 then 750 mg q8h.
Hezode C, et al. N Engl J Med. 2009;360:1839-1850. Graphic courtesy of Dr. Ira Jacobson.
      C208 Study—Telaprevir q8h vs q12h and
         PEG IFN alfa-2a vs 2b + RBV (N = 161)
                           Response-Guided Therapy
                                                                               T 1125 mg q12h +
                                                                               P -2a 180 µg/wk +
                                                                               R 1000–1200 mg/d

                                                                               T 1125 mg q12h +
                                                                               P -2b 1.5 µg/kg/wk +
                                                                               R 800–1200 mg/d

                                                                               T 750 mg q8h +
                                                                               P -2a 180 µg/wk +
                                                                               R 1000–1200 mg/d


                                                                               T 750 mg q8h +
                                                                               P -2b 1.5 µg/kg/wk +
                                                                               R 800–1200 mg/d

Abbreviations: P, peginterferon; R, ribavirin; T, telapravir.
Forns X, et al. Journal of Hepatology. 2010;52(suppl 1):S26. Graphic courtesy of Dr. Ira Jacobson.
                     PROVE3—Study Design
                         Prior Treatment Failures
      Weeks   0           12             24            36             48            60               72

   T12/P24
            T+P+R               P+R                Follow-up
  (n = 115)

 T24/PR48
  (n = 113)           T+P+R                          P+R                       Follow-up


   T24/P24
  (n = 111)              T+P                       Follow-up

      PR48
  (n = 114)       Placebo + P + R                    P+R                       Follow-up


      Weeks 0              12            24            36             48            60               72

Patients who failed previous treatment with at least 1 adequate course of PEG IFN combination with
RBV defined as at least 12 weeks of therapy.

Abbreviations: R, ribavirin 1000–1200 mg/d; P, peginterferon -2a 180 µg/wk; T, telaprevir 1125 mg
day 1 then 750 mg q8h.
McHutchison JG, et al. N Engl J Med. 2010;362:1292-1303.
 PROVE3—SVR by Prior Response and
      Treatment Group (ITT)
                                                                                    T12/PR24
               100
                       • SVR durable at 1 year
                                                                                    T24/PR48
                       • Equivalent efficacy in cirrhotics
               90                                                                   T24/P24 (no RBV)
               80                                                       76          PR48
                                                              69
               70
     SVR (%)




               60

               50
                                                                                  42
                          39        38
               40

               30
                                                                                           20
               20
                                             11        9
               10              a         a        b                a         a         b
                     n = 26/66     24/64     7/62     6/68   29/42     31/41     16/38     8/41
                0

                          Prior Nonresponders                      Prior Relapsers
aP<.001; bP = .02, all vs PR48 control group.
Graphic Courtesy of Dr. John McHutchison. McHutchison JG, et al. N Engl J Med. 2010;362:1292-1303.
        Rollover Study (107) in Treatment Failures
           From Control Arms of PROVE 1/2/3

                        T12/PR24
                        T12/PR48




                  49/8118/34       4/24 15/27       15/25 0/3   24/25 3/3   6/7   0/1




Berg T, et al. 45th EASL;April 14-18, 2010. Abstract 108.
  Sprint 1—Boceprevir + PEG IFN -2b + RBV
             International, Phase II, Treatment-Naive, Geno 1


             Control                        P + R (n = 104)                       Follow-up
   Part 1




                        PR       P + R + B (n = 103)                 Follow-up
             Lead-in
                        PR                   P + R + B (n = 103)                  Follow-up

                 No          P + R + B (n = 107)                     Follow-up
             Lead-in
                                          P + R + B (n = 103)                     Follow-up
   Part 2b




                                            P + R (n = 16)                        Follow-up
              R-LD
                                          P + R-LD (n = 59)                       Follow-up

              Weeks 0        4      12a                28       36      48            60             72

aInterimanalysis; bPart 2 consisted of 75 patients in 10 US sites, 1:4 randomization.
Abbreviations: B, boceprevir 800 mg TID; P, PEG IFN -2b 1.5 µg/kg/wk; R, ribavirin 800–1400 mg/d;
R-LD, low-dose ribavirin 400–1000 mg/d.
Kwo P, et al. J Hepatol. 2009;50:S4.
                       SPRINT 1—SVR 24 Rates
               100
                     Part 1                                                Part 2

                80                                     75
                                                                67
     SVR (%)




                60                 56       54
                                                                             50

                40      38                                                             36


                20


                 0
                        PR         PRB a     PRBb      PRB c     PRBc         PR        PR-LD
                      Control     Lead-In No Lead-In Lead-In No Lead-In     Control    (n = 59)
                     (n = 104)   (n = 103) (n = 107) (n = 103) (n = 103)    (n = 16)
                                   Tx 28 Weeks                   Tx 48 Weeks
aP= 0.005; bP = 0.013; cP <.0001, compared with PR Control.
Kwo P, et al. J Hepatol. 2009;50:S4.
 Relapse and Breakthrough in SPRINT 1
                                 Reduction with Lead-in
                        40
                                                                                     PR48
                                                                                     PRB28
                                                                30                   PR4-PRB24
                        30
                                                                                     PRB48
                                                          24         24              PR4-PRB44
              Percent




                        20

                                          12
                        10        7                                          7
                                      4         5
                                                                                 3
                             0
                         0
                             Breakthrough                       Relapse


Kwo P, et al. J Hepatol. 2009;50:S4. Graphic courtesy of Dr. Ira Jacobson.
         SPRINT 1—SVR 24 in Those Who
                 Achieved RVR
                             100
                     100                                       94

                                          82                             84
                      80                          74
           SVR (%)




                      60

                      40

                      20

                             8/8        54/66    32/43        62/66    32/38
                       0
                              PR         PRB       PRB         PRB       PRB
                            Control     Lead-In No Lead-In    Lead-In No Lead-In
                           (n = 104)   (n = 103) (n = 107)   (n = 103) (n = 103)

                                         Tx 28 Weeks           Tx 48 Weeks
Kwo P, et al. J Hepatol. 2009;50:S4.
Graphic courtesy of Dr. Paul Kwo.
     SPRINT 1—Null Responders to PEG/RBV
      Can Have SVR with a Protease Inhibitor
                             PR4/PRB24
                             PR4/PRB44
                                                                                    b
                                                                             a




             2/7          5/21          3/10           8/11          14/21      10/12        11/11         3/3
                   4/9           8/13          11/17          8/10        11/14      14/17        11/12          9/9

              <0.5        0.5–<1.0      1.0–<1.5       1.5–<2.0      2.0–<3.0    3.0–<4.0      ≥4.0       Undetect-
                                                                                                            able
                         Log10 Viral Load Decrease After 4-Wk PR Lead-in
a1patient who was positive at wk 24 became undetectable at wk 30 onwards; b2 patients were missing
PCR at wk 24, but later had undetectable PCR.
Kwo PY, et al. Hepatology. 2009;50(4 Suppl):331A.
                           HCV RNA Polymerase
          Nucleosides and Non-Nucleoside Inhibition
                                    Allosteric
                                    GTP-binding sites                    Thumb
                      Fingers




        NNI
                                                                                 Thumb
                                                                               inhibitors




          Catalytic site
           Nucleoside
                                                                         NNI
            analogs
                                                Palm

With permission from Bressanelli S, et al. J Virol. 2002;76:3482-3492.
    NS5B Polymerase Inhibitor Overview
                    Efficacy

   Many agents with antiviral activity,
    increased with PEG IFN + RBV
   Nucleosides appear active across
    genotypes
   Some non-nucleosides have potency
    gradient across genotypes and even G1
    subtypes
     NS5B Polymerase Inhibitor Overview
                                            Efficacy
•    Phase II trials
       – Nucleos(t)ide polymerase inhibitors (RG7128 +
         PEG FN alfa + RBV)
                  RVR in 85% with RG7128 + SOC vs 10% with
                   SOC alone1
       – Nonnucleos(t)ide polymerase inhibitors (filibuvir,
         ANA598, GS 9190, ABT-333) + PEG IFN alfa + RBV
                  Higher rates of RVR (40%–75%) vs SOC2,3




1. Lalezari J, et al. J Hepatol. 2008;48:S29. 2. Jacobson I, et al. J Hepatol. 2009;48:S382-S383.
3. Rodriguez-Torres M, et al. Hepatology. 2009;50(4 suppl):LB6.
            NS5B Polymerase Inhibitor Overview
                            Resistance and Adverse Effects
•     Differences in genetic barrier to resistance class:
      nucleosides have high barrier
•     Resistance can be minimized by combining with
      PEG IFN + RBV
•     Different resistance mutation patterns suggest
      potential for combinations of polymerase inhibitors
•     Toxicity issues with earlier agents: GI effects,
      hepatotoxicity, hematologic toxicity, and visual
      disturbance


1. Shi ST, et al. Antimicrob Agents Chemother. 2008;52:675-683. 2. Lawitz E, et al. J Hepatol. 2009;50(suppl 1):S37.
3. Nelson D, et al. J Hepatol. 2008;48:S371. 4. McCown MF, et al. Antimicrob Agents Chemother. 2008;52:1604-1612.
5. Lalezari J, et al. J Hepatol. 2008;48:S29. 6. Bavisotto L, et al. Hepatology. 2007;46 (suppl 1):255A. 7. Cooper C, et al.
Hepatology. 2007;46(suppl 1):LB11.
                 Highlights from EASL 2010
                                 Protease Inhibitors
• Good activity for telaprevir against genotype 21
   – 3.7-log decline with 2 weeks of telaprevir monotherapy

• Ritonavir boosting lowers dose needed for RG7227, a protease
  inhibitor2
• Development of a protease inhibitor (MK-5172) with in vitro
  activity against resistant variants R155K, A156T, D168V3
• Excellent activity of a protease inhibitor (BI 201335) in
  nonresponders to PEG IFN + RBV with low breakthrough rates4
      – RVR 62%–69% with 240 mg QD or BID, with or without 3-day
        lead-in
      – Viral rebound at 12 weeks 16%–22%

1. Foster GR, et al. 45th EASL;April 14-18, 2010. Abstract 206. 2. Gane E, et al. 45th EASL;April 14-18,
2010. Abstract 144. 3. Carroll S, et al. 45th EASL;April 14-18, 2010. Abstract 128. 4. Sulkowski M, et al.
45th EASL;April 14-18, 2010. Abstract 298.
                 Highlights from EASL 2010
                        NS5B and NS5A Inhibitors
•     SVR data for a nucleoside (RG7128) in genotypes 2,31
       – 13/20 (65%) prior treatment failures had SVR
•     Robust nonnucleoside with high barrier to resistance
      (VX-222)2
       – >3-log decline in HCV RNA with 3 days of dosing
•     Promise for NS5A inhibitors4
       –     Up to 92% RVR with BMS-790052 in dose ranging
             study with Peg IFN + RBV



1. Gane EJ, et al. 45th EASL;April 14-18, 2010. Abstract 143. 2. Rodriguez-Torres M, et al. 45th EASL;April
14-18, 2010. Abstract 137. 3. Jacobson I, et al. 45th EASL;April 14-18, 2010. Abstract 5.
4. Pol S, et al. 45th EASL;April 14-18, 2010. Abstract 297.
                 Highlights from EASL 2010
                                 NonSTAT-C Drugs

 •     Intravenous silibin for partial responders1

 •     Potential role for immune stimulation (GI5005,
       TLR-9 agonist)2,3
 •     Increased SVR with vitamin D (86% vs 41%, n = 27)4
 •     Nitazoxanide in nonresponders (SVR 7%)5
 •     Cyclophilin Inhibitor Debio 025 can induce SVR ±
       Peg IFN after a four week course (four patients)

1. Biermer M, et al. 45th EASL;April 14-18, 2010. Abstract 142. 2. Jacobson I, et al. 45th EASL;April 14-
18, 2010. Abstract 6. 3. Muir A, et al. 45th EASL;April 14-18, 2010. Abstract 138. 4. Mouch SA, et al.
45th EASL;April 14-18, 2010. Abstract 204. 5. Shiffman ML, et al. 45th EASL;April 14-18, 2010. Abstract
296.
        INFORM-1 Study—Median Change
           from Baseline Cohorts B–G




Abbreviation: TF, treatment failure.
With permission from Gane EJ, et al. Hepatology. 2009;50(4 suppl):394A-395A.
 The Goal of IFN-Free Combination Regimens


                  A
                  A               +     B        +           C



                 Profound                          Prevention of
                suppression                           emergent
             of broad range of                       resistance
               viral variants,                    (pre-existing or
           including pre-existing                     de novo)

 •     Different drugs may contribute variably to each of these goals
 •     Not all components have to be STAT-C agents
Graphic courtesy of Dr. Ira Jacobson.
           New Anti-HCV Therapies
             Anticipated Developments
• Approval of telaprevir/boceprevir seems likely in 2011
• Other direct antivirals and compounds with novel
  mechanisms of action in development
• Response-guided therapy
• Incorporation of genetic testing
• Accelerated development of interferon-free
  combinations
• The question for clinicians: to wait or not to wait?
               ARS Question:
   Among your genotype 1 patients, how
 frequently will you be incorporating novel
      agents once they are approved?

1)   Always
2)   Very Often
3)   Sometimes
4)   Rarely
5)   Never

				
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