1 / 13

Investigational Agents for HCV: I Thought This Was Going To Get Easier

Investigational Agents for HCV: I Thought This Was Going To Get Easier. Susanna Naggie, MD Assistant Professor of Medicine Duke Clinical Research Institute Durham, NC. From S Naggie , MD, at Washington, DC: June 18, 2013, IAS-USA. HIV & HCV. 10 million people worldwide

tao
Download Presentation

Investigational Agents for HCV: I Thought This Was Going To Get Easier

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. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Investigational Agents for HCV: I Thought This Was Going To Get Easier Susanna Naggie, MDAssistant Professor of MedicineDuke Clinical Research InstituteDurham, NC From S Naggie, MD, at Washington, DC: June 18, 2013, IAS-USA.

  2. HIV & HCV • 10 million people worldwide • 30% of US patients with HIV have HCV Hepatitis C 180 million HIV 40 million Staples CT. Clin Infect Dis 1999

  3. D:A:D Study: Liver-Related Deaths in Persons with HIV 14.5% DAD Study Group, Arch Intern Med 2006

  4. HAART Era: Cirrhosis Risk Thein et al. AIDS 2008; 22:1979

  5. Higher Health Care Utilization for HIV/HCV Katrak et al. CROI 2013 Abstract P219

  6. NS3 Protease Inhibitors • Serine protease (HIV aspartyl) • Peptidomimetic • Linear • Macrocyclic • High Potency • Low barrier to resistance • First Wave GT 1 • Second Wave Multigenotypic (GT 3)

  7. NS5B Polymerase Inhibitors • Nucleoside (NI) vs Non-nucleoside (NNI) • Moderate-High Potency • Higher genetic barrier to resistance • Multi- or pangenotypic • Use in combination therapy • 2-3 drugs • Use in IFN-sparing/free

  8. Activity in replication unknown Multiple possible mech of action Multi- to pangenotypic Moderate Potency Barrier to resistance Use in IFN-sparing/free NS5A Inhibitors

  9. Telaprevir and Boceprevir In HCV Mono-Infected Subgroups: Phase III Summary 100 75-83[1,2] 80 63-74[7,8] 68-75[3,4] 53-62[3-4] 60 52-59[1,2] SVR (%) 29-38[1,6] 40 20 14[5]* 0 Relapser Naive White/ Nonblack Naive Black Partial Responder Null Responder Cirrhotic Null Responder HIV-coinfected Naive *Pooled TVR arms of REALIZE trial. ZeuzemS, et al. N Engl J Med. 2011;364:2417-2428. 2. Bacon BR, et al. N Engl J Med. 2011;364:1207-1217. 3. Jacobson IM, et al. N Engl J Med. 2011;364:2405-2416. 4. Poordad F, et al. N Engl J Med. 2011;364:1195-1206. 5. Zeuzem S, et al. EASL 2011. Abstract 5. 6. Vierling JM, et al. AASLD 2011. Abstract 931. 7. Sulkowski MS, et al. Lancet Inf Dis 2013 [Epub]. 8. Sulkowski MS, et al. Ann Int Med 2013 [Epub].

  10. PK Interactions: Telaprevir & ART Van Heeswijk et al. CROI 2011 Ab#119, ICAAC 2011 Ab# A1-1738a; KakudaClin Pharm 2012 Ab# O_18 Johnson Clin Pharm 2013 Ab#O_07, VourvahisClin Pharm 2013 Ab#O_17

  11. PK Interactions: Boceprevir & ART Kasserra et al. 18th CROI 2011 Ab# 118; Hulskotte et al. 19th CROI 2012 Ab# 771LB; Hammond Clin Pharm 2012 Ab# O_15 GarraffoClin Pharm 2013 Ab#O_15, , VourvahisClin Pharm 2013 Ab#O_17

  12. What about SOF in HIV/HCV? • Phase IIB • SOF + P/R X 12W • Naïve, GT 1-3 • NCT01565889 • Phase III • SOF + WBR X 12-24W • Naïve GT 1-4, Experienced GT 2,3 • 20% Cirrhotic Kirby et al. AASLD 2012 Abstract #1877

  13. Simeprevir and ART? Phase III Study: Rilpivirine (15%), Raltegravir (87%), Maraviroc, Enfuvirtide, NRTIs Ouwerkerk-Mahadevan et al. IDSA 2012 Abstract #49

More Related