1 / 22

The next generation of Treatment for Hepatitis C

The next generation of Treatment for Hepatitis C. Treatment of CHC: Outcomes. Goal of therapy is to render the patient PCR negative for HCV RNA Need to remain PCR negative 6 months after end of therapy Response rates for combination therapy Genotype 1 up to 40% Genotypes 2 or 3 up to 80%.

jerry
Download Presentation

The next generation of Treatment for Hepatitis C

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. The next generation of Treatment for Hepatitis C

  2. Treatment of CHC: Outcomes • Goal of therapy is to render the patient PCR negative for HCV RNA • Need to remain PCR negative 6 months after end of therapy • Response rates for combination therapy • Genotype 1 up to 40% • Genotypes 2 or 3 up to 80%

  3. Evolution of HCV genotype 1 treatment 100 80 • 42–54% Peg-IFN + RBV2–4 • 16–28% 60 IFN + RBV1 SVR rate (%) • 2–7% IFN1 40 20 1990 2000 2020 2010 • IFN: interferon; RBV: ribavirin Peg-IFN: peginterferonDAA: direct-acting antiviralSVR: sustained virologic response 1. McHutchison JG, et al. N Engl J Med 1998;339:1485–92; 2. Fried M, et al. N Engl J Med 2002;347:975–823. Manns MP, et al. Lancet 2001;358:958–65; 4. Hadziyannis SJ, et al. Ann Intern Med 2004;140:346–555. Jacobson IM, et al. Hepatology 2010;52(Suppl):427A; 6. Sherman KE, et al. Hepatology 2010;52(Suppl.):401A7. Poordad F, et al. Hepatology 2010;52(Suppl.):402A; 8. Foster GR, et al. Hepatol Int 2011;5(Suppl.1):14

  4. Treatment Issues • Genotypes 2/3 – nothing new on horizon • Genotype 1 – failure rate 50-60% • No good options for treatment failures

  5. New treatment for Genotype 1 HCV(Rx naïve patients)

  6. Direct Acting Anivirals (DAAs) • DAA-based triple combination therapy led to improved SVR rates over current therapy in Phase II trials • 61–85% SVR with telaprevir-based therapy4–6 • 54–75% SVR with boceprevir-based therapy7 • Telaprevir and boceprevir have recently completed Phase III trials in treatment-naïve patients • Telaprevir: ADVANCE8 and ILLUMINATE9 • Boceprevir: SPRINT-210

  7. Pbo + PR TVR + PR PR PR PR PR Pbo + PR TVR + PR PR ADVANCE (telaprevir): study design (N=1088) PR48 (control)(N=361) SVR Follow-up SVR eRVR+ Follow-up Follow-up T12PR(N=363) eRVR– SVR Follow-up SVR eRVR+ Follow-up Follow-up T8PR(N=364) SVR eRVR– Follow-up 0 8 12 24 36 48 72 Weeks Peg-IFN alfa-2a dose: 180 µg/week; RBV dose: 1000 or 1200 mg/dayeRVR: extended rapid virologic response (undetectable HCV RNA at Weeks 4 and 12); Pbo: placebo; PR: peginterferon/ribavirin; TVR: telaprevir Jacobson IM, et al. Hepatology 2010;52(Suppl.):427A

  8. SVR SVR SVR SVR PRlead-in PRlead-in PRlead-in Follow-up PR + Placebo Follow-up Follow-up Follow-up PR + Boceprevir PR + Boceprevir PR + Placebo SPRINT-2 (boceprevir): study design (N=1097) PR48 ControlN=363 Weeks 8–24 HCV RNA undetectable BOC RGT N=368 Weeks 8–24 HCV RNA detectable* BOC44/ PR48 N=366 24 28 0 4 8 48 72 Weeks *But with undetectable HCV RNA at Week 24 Peg-IFN alfa-2b dose: 1.5 µg/kg/week RBV dose: 600–1400 mg/day in a divided daily doseRGT: response-guided therapy Poordad F, et al. Hepatology 2010;52(Suppl.):402A

  9. eRVR+ T12PR48N=160 eRVR+ T12PR24 N=162 eRVR– T12PR48 N=118 PR PR PR T12PR PR ILLUMINATE (telaprevir): study design (N=540) SVR 72 weeks Follow-up Follow-up Non-inferiority (NI) Randomized Treatments eRVR+ SVR Follow-up Assigned Treatment SVR eRVR– Follow-up 0 12 20 20 24 36 48 60 72 Weeks Patients discontinued for any reason before Week 20 randomization were categorized as ‘Other’ (N=100)Stopping rules were similar to ADVANCE Sherman KE, et al. Hepatology 2010;52(Suppl.):401A

  10. ADVANCE and ILLUMINATE: SVR rates with telaprevir-based therapy versus PR alone 72–75* T12PR 659/903 PR48 158/361 Jacobson IM, et al. Hepatology 2010;52(Suppl.):427A; Sherman KE, et al. CROI 2011. Abstract 957 *p<0.0001 vs PR48 in ADVANCE (75% versus 44%)

  11. SPRINT-2: SVR rates with boceprevir-based therapy versus PR alone BOC44/PR48 242/366 PR48 137/363 BOC RGT 233/368 For non-Black patients, p<0.0001 for both boceprevir arms versus PR48; for Black patients, p=0.044 and p=0.004 for BOC RGT and BOC44/PR48, respectively, versus PR48 Adapted from Poordad F, et al. Hepatology 2010;52(Suppl.):402A

  12. Tripple therapy works in advanced fibrosisADVANCE (telaprevir): SVR rates by fibrosis stage ADVANCE1 No, minimal or portal fibrosis Bridging fibrosis or cirrhosis SVR (%) PR48134/288 T12PR226/290 PR4824/73 T12PR45/73 n/N= 1. Jacobson IM, et al. Hepatology 2010;52(Suppl.):427A;

  13. Tripple therapy works in all IL28B genotypesADVANCE (telaprevir): SVR rates by IL28B genotype CC CT TT SVR (%) PR4820/80 T12PR48/68 PR4835/55 T12PR45/50 PR486/26 T12PR16/22 n/N= Samples were available for 454/1088 (42%) patients enrolled in ADVANCE Jacobson IM, et al. J Hepatol 2011;54(Suppl.):S542

  14. Safety and tolerability with DAAs • Common AEs with PR include:1–3 • Fatigue, headache, nausea, pyrexia and myalgia • Anemia and neutropenia • Depression, irritability and insomnia • Rash • Additional management considerations with DAAs • Telaprevir:4–6 rash, anemia • Boceprevir:7,8 anemia and dysgeusia 1. Pegintron EMA Summary of Product Characteristics; 2. Pegasys EMA Summary of Product Characteristics3. Rebetol EMA Summary of Product Characteristics; 4. Jacobson IM, et al. Hepatology 2010;52(Suppl.):427A 5. Sherman KE, et al. Hepatology 2010;52(Suppl.):401A; 6. Foster GR, et al. Hepatol Int 2011;5(Suppl. 1):147. Poordad F, et al. Hepatology 2010;52(Suppl.):402A; 8. Bacon BR, et al. Hepatology 2010;52(Suppl.):430A AE: adverse event

  15. Evolution of HCV genotype 1 treatment 100 • 59–75% DAA+Peg-IFN + RBV5–8 80 • 42–54% Peg-IFN + RBV2–4 • 16–28% 60 IFN + RBV1 SVR rate (%) • 2–7% IFN1 40 20 1990 2000 2020 2010 • IFN: interferon; RBV: ribavirin Peg-IFN: peginterferonDAA: direct-acting antiviralSVR: sustained virologic response 1. McHutchison JG, et al. N Engl J Med 1998;339:1485–92; 2. Fried M, et al. N Engl J Med 2002;347:975–823. Manns MP, et al. Lancet 2001;358:958–65; 4. Hadziyannis SJ, et al. Ann Intern Med 2004;140:346–555. Jacobson IM, et al. Hepatology 2010;52(Suppl):427A; 6. Sherman KE, et al. Hepatology 2010;52(Suppl.):401A7. Poordad F, et al. Hepatology 2010;52(Suppl.):402A; 8. Foster GR, et al. Hepatol Int 2011;5(Suppl.1):14

  16. What about Genotype 1 patients with previous treatment failure?

  17. Definitions of failure on prior Peg-IFN/RBV therapy Null response Relapse Non-response 2 log10 drop HCV RNA level Partial response Detection limit Treatment Adapted from Shiffman M. Curr Gastroenterol Rep 2006;8:46–52Neumann A, et al. Science 1998;282:103–7; De Bruijne J, et al. Neth J Med 2008;66:311–22

  18. REALIZE (telaprevir): SVR in prior relapsers, partial responders and null responders Prior relapsers Prior partialresponders Prior null responders * * * * SVR (%) * * LI T12/PR4826/48 T12/PR4829/49 PR48 4/27 PR48 2/37 LI T12/PR4825/75 T12/PR4821/72 PR48 16/68 LI T12/PR48124/141 T12/PR48121/145 n/N= *p<0.001 vs PR48; post-hoc analysis Foster GR, et al. Hepatol Int 2011;5(Suppl. 1):14

  19. RESPOND-2 (boceprevir): SVR in prior relapsers and partial responders Prior relapsers Prior partialresponders Prior null responders were excluded from RESPOND-2 SVR (%) BOCRGT 23/57 BOC44/PR4830/58 PR48 2/29 PR48 15/51 BOC RGT 72/105 BOC44/PR4877/103 n/N= Bacon BR, et al. Hepatology 2010;52(Suppl.):430A

  20. Summary of Tripple therapy with DAAs • Only for Genotype 1 Hepatitis C • Uses Peg Inf + Ribavirin + DDA • Improved response in naïve patients (65-75%) • Improved response in prior non-responders • Improved response in difficult to treat groups

  21. COST • Cost of treatment • genotype 1 £12,782 for 48 weeks treatment • genotype 2 or 3 £5,233 for 24 weeks • Supportive therapy with: • Epoetin - 8000 units twice weekly = £3,216 for 6 months • G-CSF - Neupogen 30million units/wk = £1752 for 6 months • Cost of addition of DAA £14,000 - £24,000 • To be confirmed Sept 2011

  22. Who will get the new drugs?

More Related