Slide 1 of 8 From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA. IAS–USA Marion G....
8
Slide 1 of 8 From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA. IAS–USA Marion G. Peters, MD John V. Carbone, MD, Endowed Chair Professor of Medicine Chief of Hepatology Research University of California San Francisco Hepatitis C Virus (HCV) Coinfection: New Drugs, New Strategies From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA.
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Transcript of Slide 1 of 8 From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA. IAS–USA Marion G....
Slide 1 of 8
From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA. IAS–USA
Marion G. Peters, MDJohn V. Carbone, MD, Endowed Chair
Professor of MedicineChief of Hepatology Research
University of California San Francisco
Hepatitis C Virus (HCV) Coinfection:
New Drugs, New Strategies
From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA.
Slide 2 of 8
From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA.
The Long-Awaited New Era:Protease Inhibitors for HCV Genotype 1
SVR >70%Genotype 1
Response-guided therapy(RGT)
Side effects Resistance
April 27-28, 2011: FDA Advisory Panel voted 18-0 for approval of boceprevir and telaprevir
Both drugs approved by FDA May 2011
Drug-druginteractions
Slide 3 of 8
From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA.
1
2
3
4
5
6
7
8
0 12 24 36 48 60 72
Week of Treatment
HCV
RN
A (lo
g IU
/ml)
Different Types of “Non-Response”
Null
Partial BreakthroughRelapse
Adapted from M. Shiffman
Slide 4 of 8
From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA.
ETR SVR
724 48
ViralRNA (–)
0 12 24
EVR: Partial versus CompleteRGT= response guided therapy
Wks of Therapy
HC
V R
NA
(lo
g co
pie
s/m
L)
6
cEVR
5
4
3
2
RVR
eRVR: ud at weeks 4 and 12
Slide 5 of 8
From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA.
Similarities/ Differences in Phase III Studies of TVR and BOC in GT1 Naive Mono Pts
Parameter TVR[1] BOC[2]
PR lead-in? No Yes: 4 wks
PegIFN alfa formulation 2a 2b
PI dosing requirements TID; administer with fatty meal
TID with food not low fat
Duration of PI triple therapy 8-12 wks followed by 12-40 wks PR
24-44 wks after 4 wks PR lead-in
Qualification for shortened therapy (response guided)
Undetectable HCV RNA Wk 4 and 12 of
triple therapy
Undetectable HCV RNA w8 and w24 of
triple therapy
Qualified for shortened therapy, % 58 (24 wks) 44 (28 wks)
SVR, % 69-75 63-66
Relapse, % 9 9
Adverse events more frequent in PI arms
Rash, anemia, pruritus, nausea Anemia, dysgeusia
1. Jacobson IM, et al. AASLD 2010. Abstract 211. 2. Poordad F, et al. AASLD 2010. Abstract LB-4. ccoptions.com, Zeuzem
Slide 6 of 8
From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA.
Various Paradigms BeingDeveloped Simultaneously
PEG IFN +Ribavirin + Single DAA
• PIs• Nucs• NS5A• Cyclophilin antagonist
PEG IFN +Ribavirin +
DAA-1 +DAA-2
IFN-freeregimens
• Some trials involve more than one of these designs• PEG IFN lambda being evaluated• Proof of concept for curative potential of IFN-free regimens had been established
Slide 7 of 8
From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA.
Issues in HCV therapy• Genotype differences
– 2 versus 3 versus 1– 1a poorer response than 1b
• Easier to develop resistance
• IL28b response– CC versus TT
• Prior exposure to IFN and DAA• Extent of liver disease• DDI
Slide 8 of 8
From MG Peters, MD, at Los Angeles, CA: April 22, 2013, IAS-USA.
HCV and HIV coinfected• Select who to treat
– Moderate to severe fibrosis F3-4• Assess fibrosis
– Liver biopsy– Serum tests APRI FIB-4– Transient elastography
• Control HIV• Encourage adherence• Avoid alcohol
