update on the hcv antiviral pipeline n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Update on the HCV Antiviral Pipeline PowerPoint Presentation
Download Presentation
Update on the HCV Antiviral Pipeline

Loading in 2 Seconds...

play fullscreen
1 / 14

Update on the HCV Antiviral Pipeline - PowerPoint PPT Presentation


  • 68 Views
  • Uploaded on

Update on the HCV Antiviral Pipeline. Todd S. Wills, MD SPNS HCV Treatment Expansion Initiative Evaluation and Technical Assistance Center Infectious Disease Specialist. HCV Response Rates in HIV+ and HIV- Patients Treated With PegIFN /RBV. APRICOT HIV Positive Overall SVR: 40%. PRESCO

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Update on the HCV Antiviral Pipeline' - palma


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
update on the hcv antiviral pipeline

Update on the HCV Antiviral Pipeline

Todd S. Wills, MD

SPNS HCV Treatment Expansion Initiative

Evaluation and Technical Assistance Center

Infectious Disease Specialist

hcv response rates in hiv and hiv patients treated with pegifn rbv
HCV Response Rates in HIV+ and HIV- Patients Treated With PegIFN/RBV

APRICOT

HIV Positive

Overall SVR: 40%

PRESCO

HIV Positive

Overall SVR: 50%

FRIED

HIV Negative

Overall SVR: 56%

100

76

80

72

62

60

46

Patients With SVR (%)

36

40

29

20

176 95 191 152 298 140

n =

0

GT1/4

GT2/3

GT1/4

GT2/3

GT1/4

GT2/3

48 Wks of Therapy,600 mg RBV

24, 48, or 72 Wks of Therapy,Weight-Based RBV

48 Wks of Therapy,Weight-Based RBV

Soriano V, et al. Care of patients coinfected with HIV and hepatitis C virus: 2007 updated recommendations from the HCV–HIV International Panel AIDS. 2007;21:1073-1089.

slide3

Potential HCV antiviral targets

C

E1

E2/NS1

NS2

NS3

NS4A

NS4B

NS5A

NS5B

5’

3’

Internal

ribosomal

entry site

RNA

binding

site

Envelope

glyco-

proteins

Signal

peptide

Serine protease/

helicase

RNA dependent

RNA polymerase

telaprevir, boceprevir

adherence
Adherence
  • Triple therapy presents challenges with already busy schedules[143]
    • TID dosing
    • Food requirements
  • Data show pegIFN/RBV adherence decreases over time[5]
    • Addition of PIs may exacerbate this trend

1. Telaprevir [package insert]. May 2011. 2. Boceprevir [package insert]. May 2011. 3. EMA. Boceprevir [package insert] 2011.4. EMA. Telaprevir [package insert] 2011. 5. Lo Re V 3rd, et al. Ann Intern Med. 2011;155:353-360.

from Clinical Care Options

study 110 high rates of early response with tvr pr in coinfected patients
Study 110: High Rates of Early Response With TVR + PR in Coinfected Patients
  • Similar efficacy results observed with or without concurrent ART
  • Nausea, pruritus, dizziness, fever more common with TVR vs placebo
  • Pharmacokinetic interactions with ATV or EFV not clinically significant

Undetectable HCV RNA, Week 4 (ITT)

Undetectable HCV RNA, Week 12 (ITT)

No ART

ATV/RTV-based ART

EFV-based ART

Total

100

100

75

75

71

71

80

80

70

68

64

57

60

60

Undetectable HCV RNA (%)

Undetectable HCV RNA (%)

40

40

17

14

12

20

12

12

20

5

0

0

0

0

12/16

9/14

26/37

5/7

0/6

1/8

0/8

1/22

12/16

8/14

25/37

n/N =

5/7

1/6

1/8

1/8

3/22

n/N =

Telaprevir + PR

PR

Telaprevir + PR

PR

Sulkowski M, et al. CROI 2011. Abstract 146LB.

study 110 svr 12 data
Study 110 – SVR 12 Data

Dieterich D, et al. CROI 2012 Abstract 46

telaprevir plus peginf and ribavirin in hiv hcv infected patients side effects
Telaprevir plus PegINF and Ribavirin in HIV/HCV Infected Patients – Side Effects

*no cases of severe rash

Sherman, KE et al.. AASLD Conference November 2011 – Late Breaker Abstract 8

boceprevir in addition to pegylated inf alfa 2a in hiv hcv patients on arvs
Boceprevir in Addition to Pegylated INF alfa 2a in HIV/HCV Patients on ARVs

Sulkowski, M. CROI 2012 Abstract 47

psi 7977 phase ii trial data
PSI-7977 – Phase II Trial Data

HCV uridine nucleotide analogue

Genotype 1

Genotype 2/3

Lawritz, E. et al. J of Hepatology 54 (s1) 2012

tmc 435 phase iib trial data
TMC-435 – Phase IIb trial data
  • HCV NS3/4A Protease Inhibitor (Once-Daily)
  • Prior Treatment Failures

100 mg

Zeuzem S., et al. J of Hepatology 54 (s1) 2012

150 mg

P<0.001 vs placebo

interferon sparing strategies
Interferon Sparing Strategies
  • ABT 450/r – ritonovir boosted HCV PI +
  • ABT 072 – HCV polymerase inhibitor +
  • Weight-based ribavirin
  • Open label 12 week treatment trial 11 patients
  • Interferon sparing
  • 91% SVR24
  • One patient relapsed 8 weeks post Rx
  • All patients were IL28B CC

Lawitz, E. et al. Of Hepatology 56(s1) 2012

interferon and ribavirin sparing strategies
Interferon AND Ribavirin Sparing Strategies
  • Daclatasvir (NS5A replication complex inhibitor) +
  • Asunaprevir (HCV NS3 PI)
  • Open label trial of both drugs in 43 prior null responders or with IFN/R intolerance

Suzuki, F. et al. J of Hepatology 56 (s1) 2012