Review the current benefits and limitations with protease inhibitor-based HCV therapies, and the emerging data on potential future regimens, and the advances they represent

1. The Beckoning Future:
How Hepatitis C Drugs in Development
May Affect Practice Today and Tomorrow
This program is supported by educational grants from
Originally posted 11/15/2011 at clinicaloptions.com/ss/HCVFuture

2. How Hepatitis C Drugs in Development May Affect Practice Today and Tomorrow
clinicaloptions.com/hepatitis
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3. How Hepatitis C Drugs in Development May Affect Practice Today and Tomorrow
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Program Faculty
Program Director: Eric Lawitz, MD, CPI
Medical Director
Stefan Zeuzem, MD Alamo Medical Research
Professor of Medicine Hepatologist
Chief, Department of Medicine I Camden Medical Center
JW Goethe University Hospital San Antonio, Texas
Frankfurt, Germany
Faculty: Andrew J. Muir, MD, MHS
Nezam H. Afdhal, MD, FRCPI Associate Professor of Medicine
Division of Gastroenterology
Associate Professor of Medicine
Director, Gastroenterology/Hepatology
Harvard Medical School
Research
Chief of Hepatology
Duke Clinical Research Institute
Beth Israel Deaconess Medical Center
Duke University School of Medicine
Boston, Massachusetts
Durham, North Carolina

4. How Hepatitis C Drugs in Development May Affect Practice Today and Tomorrow
clinicaloptions.com/hepatitis
Faculty Disclosures
Nezam H. Afdhal, MD, FRCPI, has disclosed that he has received consulting
fees from Biogen, Biolex, Boehringer Ingelheim, Echosens, Fibrogen, Gilead
Sciences, GlaxoSmithKline, Human Genome Sciences, Idera Pharmaceuticals,
Ligand, Merck/Schering-Plough, Novartis, Spring Bank, and Vertex; and has
contracted research with Echosens, Gilead Sciences, GlaxoSmithKline,
Merck/Schering-Plough, Novartis, Quest, and Vertex.
Eric Lawitz, MD, CPI, has disclosed that he has received research or grant
support from Abbott, Achillion, Anadys, Biolex, Boehringer Ingelheim, Bristol-
Myers Squibb, Gilead Sciences, GlaxoSmithKline, GlobeImmune, Idenix
Pharmaceuticals, Idera Pharmaceuticals, Inhibitex Pharmaceuticals, Medarex,
Medtronic, Merck, Novartis, Pharmasset, Pfizer, Roche, Schering-Plough,
Santaris Pharmaceuticals, Scynexis Pharmaceuticals, Tibotec/Janssen
Therapeutics, Vertex, ViroChem Pharma, and ZymoGenetics; is on the speaker’s
bureaus for Gilead Sciences, Merck, and Vertex; and is on the advisory board for
Abbott, Achillion, Anadys, Biolex, GlobeImmune, Inhibitex, Merck, Pharmasset,
and Tibotec/Janssen Therapeutics.

5. How Hepatitis C Drugs in Development May Affect Practice Today and Tomorrow
clinicaloptions.com/hepatitis
Faculty Disclosures
Andrew J. Muir, MD, MHS, has disclosed that he has received grant or research
support from Abbott, Anadys, Gilead Sciences, GlaxoSmithKline, Idera
Pharmaceutical, Inc, Medtronic, Merck, Pfizer, Pharmasset, Roche, Scynexis,
Santaris, Three Rivers Pharma, Vertex, and Zymogenetics; and has received
consulting fees from Bristol-Myers Squibb, Merck, Pharmasset, Salix, Santaris,
Vertex, and Zymogenetics.
Stefan Zeuzem, MD, has disclosed that he has received consulting fees from
Abbott, Anadys, Achillion, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead
Sciences, iTherX, Janssen Therapeutics, Merck, Novartis, Pfizer, Pharmasset,
Roche, Santaris, and Vertex; and has received fees for non-CME services from
Bristol-Myers Squibb, Gilead Sciences, Novartis, Merck, and Roche.

6. Today’s Direct-Acting Antivirals:
Benefits and Limitations
Nezam H. Afdhal, MD, FRCPI
Associate Professor of Medicine
Harvard Medical School
Chief of Hepatology
Beth Israel Deaconess Medical Center
Boston, Massachusetts

7. How Hepatitis C Drugs in Development May Affect Practice Today and Tomorrow
clinicaloptions.com/hepatitis
To Treat or Not to Treat:
A Constellation of Considerations
Genotype: Histologic stage
Duration of
virus, 20%+ lifetime risk
infection
patient (IL28B) of cirrhosis
Personal plans
Family and
(marriage, Age
other support
pregnancy)
Patient mindset ALT Occupation
Extrahepatic Contraindications
features HIV coinfection & comorbidities;
(fatigue, EMC, PCT) insulin resistance

8. How Have Boceprevir and
Telaprevir Improved HCV Care?

9. How Hepatitis C Drugs in Development May Affect Practice Today and Tomorrow
clinicaloptions.com/hepatitis
Boceprevir or Telaprevir + PegIFN/RBV:
The New Standard of Care for Genotype 1
 Potent inhibitors of HCV NS3/4A protease
 Both approved by FDA and EMA in mid 2011
– Indicated in combination with pegIFN/RBV for treatment of
genotype 1 HCV–infected patients
– Previously untreated or previous treatment failures
Telaprevir [package insert]. May 2011. Boceprevir [package insert]. May 2011.
EMA. Telaprevir [package insert] 2011. EMA. Boceprevir [package insert] 2011.

10. How Hepatitis C Drugs in Development May Affect Practice Today and Tomorrow
clinicaloptions.com/hepatitis
Telaprevir in Genotype 1 Patients
 750 mg (two 375-mg tablets) q8hr with food (not low fat; standard fat meal is 21 g, eg,
1/2-cup nuts or 2-oz cheddar cheese)
Treatment Naive and Previous Relapsers
eRVR; stop at Wk 24
TVR + PR PR
No eRVR; PR
Previous Partial or Null Responders
TVR + PR PR
0 4 12 24 48
 Treatment-naive patients with compensated cirrhosis and eRVR may benefit from
additional 36 wks of pegIFN + RBV (ie, to Wk 48)
Time Point Criterion Stopping Rule
Wk 4 or 12 HCV RNA > 1000 IU/mL Discontinue all therapy
Wk 24 Detectable HCV RNA Discontinue PR
Any Discontinuation of PR for any reason Discontinue TVR
Telaprevir [package insert]. May 2011. EMA. Telaprevir [package insert] 2011.

11. How Hepatitis C Drugs in Development May Affect Practice Today and Tomorrow
clinicaloptions.com/hepatitis
Boceprevir in Genotype 1 Patients
 800 mg (four 200-mg capsules) q8hr with meal or light snack
Treatment Naive
BOC + PR Early response; stop at Wk 28
PR
BOC + PR PR
Previous Relapsers or Partial Responders
Early response;
BOC + PR stop at Wk 36
PR
BOC + PR PR
0 4 8 12 24 28 36 48
Wks
 All cirrhotic patients should receive lead-in followed by PR + BOC for 44 wks
 If considered for treatment, null responders should receive lead-in then PR + BOC for 44 wks
 EMA label recommends fixed-duration therapy for all trt-expd patients: LI + 32 wks triple + 12 wks PR
Time Point Criterion Stopping Rule
Wk 12 HCV RNA ≥ 100 IU/mL Discontinue all therapy
Wk 24 Detectable HCV RNA Discontinue all therapy
Any Discontinuation of PR for any reason Discontinue BOC
Boceprevir [package insert]. May 2011. EMA. Boceprevir [package insert] 2011.

12. How Hepatitis C Drugs in Development May Affect Practice Today and Tomorrow
clinicaloptions.com/hepatitis
SVR Rates With BOC or TVR in
Genotype 1 Treatment-Naive Patients
100
80 63-75
60
SVR (%)
38-44
40
20
0
PegIFN/RBV BOC or TVR +
PegIFN/RBV
Poordad F, et al. N Engl J Med. 2011;364:1195-1206.
Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416.

13. How Hepatitis C Drugs in Development May Affect Practice Today and Tomorrow
clinicaloptions.com/hepatitis
High SVR Rates Across Baseline Patient
and Virus Factors
ADVANCE: TVR + PegIFN/RBV in Treatment-Naive Genotype 1
Data from T12PR arm only
100
79 78 78
74
75 71
62
SVR (%)
50
25
n/ 118/ 152/ 64/ 207/ 226/ 45/
N = 149 213 82 281 290 73
0
1b 1a < 800K ≥ 800K F0-2 F3-F4
Genotype HCV RNA (IU/mL) Fibrosis
Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416.

14. How Hepatitis C Drugs in Development May Affect Practice Today and Tomorrow
clinicaloptions.com/hepatitis
SVR Rates With BOC or TVR in
GT1 Treatment-Experienced Patients
100
PegIFN + RBV
69-83
80 BOC or TVR + PegIFN + RBV
60 40-59
SVR (%)
40 29-38
24-29
20 7-15
5
0
Relapsers Partial Responders Null
Responders
Bacon BR, et al. N Engl J Med. 2011;364:1207-1217. Zeuzem S, et al. N Engl J Med.
2011;364:2417-2428.
Vierling JM, et al. AASLD 2011. Abstract 931.

15. What New Challenges Have
Boceprevir and Telaprevir
Presented?

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