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Response Guided Vs.Response Unguided Therapy

Response Guided Vs.Response Unguided Therapy. K.Rajender Reddy M.D Professor of Medicine University of Pennsylvania Philadelphia, USA. Factors in Complexity of HCV Therapy. Race/ethnicity. No Lead In. IL28B. Partial Responder. Obesity. Lead In. Relapser. Treatment Na ï ve.

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Response Guided Vs.Response Unguided Therapy

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  1. Response Guided Vs.Response Unguided Therapy K.Rajender Reddy M.D Professor of Medicine University of Pennsylvania Philadelphia, USA

  2. Factors in Complexity of HCV Therapy Race/ethnicity No Lead In IL28B Partial Responder Obesity Lead In Relapser Treatment Naïve Age/Gender Null Responder Viral load/Genotype

  3. Easy to Treat Low viral load Women Younger age Absence of fibrosis IL 28 B CC Interferon sensitive Relapsers Difficult to Treat High viral load Obesity/Metabolic syndrome Blacks IL 28 B-C/T, T/T Cirrhosis Older population Interferon insensitive Partial and Null Responders Protease Inhibitor Based HCV Therapy:Easy to Treat and Difficult to Treat Genotype 1 Patient Populations Response Guided Therapy Response Unguided Therapy

  4. Protease Inhibitor Trials: Summary • Treatment Naïve • Telaprevir (TPV) • ADVANCE -- RGT • ILLUMINATE • RGT and RUGT • Boceprevir (BOC) • SPRINT-2 • RGT + RUGT • Treatment Experienced • Telaprevir (TPV) • REALIZE • RUGT • Boceprevir (BOC) • RESPOND-2 • RGT + RUGT

  5. Limitations and Unique Aspects of the Trials • In both TPV and BOC studies, small number of • Patients with cirrhosis • Older population • High BMI patients ( Post-Hoc Analyses) • IL-28B • Boceprevir – limited data • Telaprevir – limited data • Blacks • Boceprevir • Prospective study • Telaprevir • Post-hoc analysis • Prior Treatment Experienced • Boceprevir – RGT + RUGT • Telaprevir – RUGT

  6. ADVANCE: Overall SVR and Relapse Rates According to Treatment Arm T12PR T8PR PR % of Patients 271/363 168/361 250/364 51/189 18/247 17/264 Jacobson IM et al. N Engl J Med 2011;364:2405-2416.

  7. ADVANCE: SVR for T12PR in Selected Subgroups SVR (%) 112/ 149 150/ 214 16/ 26 159/ 214 118/ 142 244/ 325 Jacobson IM et al. N Engl J Med 2011;364:2405-2416.

  8. ADVANCE: SVR for T12PR in Selected Subgroups SVR (%) 26/ 35 245/ 328 152/ 213 118/ 149 64/ 82 207/ 281 Jacobson IM et al. N Engl J Med 2011;364:2405-2416.

  9. ADVANCE: SVR for T12PR in Selected Subgroups SVR % 109/ 134 117/ 156 32/ 52 13/ 21 129/ 155 87/ 129 55/ 77 Jacobson IM et al. N Engl J Med 2011;364:2405-2416.

  10. Cirrhosis

  11. ILLUMINATE(TPV): SVR in Cirrhosis and Blacks in those with eRVR ( T12/PR24 Vs.T12/PR48) RUGT SVR % 12/18 11/12 15/17 16/17 FDA analysis and Sherman KE, et al. N Engl J Med 2011;365:1014-24 10

  12. SPRINT-2: SVR and Relapse Rate by Fibrosis Score N=313 N=328 N=319 N=24 N=34 N=42 N=158 N=233 N=231 N=12 N=17 N=25 SPRINT-2 and RESPOND-2: BOC + PegIFN/RBV in HCV GT 1 with Advanced Fibrosis/Cirrhosis Bruno S, et al. 46th EASL; Berlin, Germany; March 30-April 3, 2011; Abst. 7.

  13. RESPOND-2: SVR by Cirrhotics (F4) vs. Non-Cirrhotics (F0/1/2/3) According to Treatment Arm PR 48 RGT BOC/PR48 RUGT % of Patients 0/10 6/17 17/22 16/66 85/132 85/128 Bacon BR et al. N Engl J Med 2011;364:1207-1217.

  14. Treatment Naïve-Blacks

  15. SPRINT-2: SVR in Primary Patient Cohorts According to Treatment Arm PR48 RGT BOC/PR48 p<0.001 RUGT p<0.001 p<0.001 p<0.001 p=0.004 p=0.04 SVR (%) 137/ 363 233/ 368 242/ 366 125/ 311 211/ 316 213/ 311 12/ 52 22/ 52 29/ 53 137/ 363 All Patients (Both Cohorts) Nonblack Cohort Black Cohort Poordad F et al. N Engl J Med 2011:364:1195-1206.

  16. Prior Treatment Experienced

  17. RESPOND-2: SVR and Relapse Rates for All Subjects According to Treatment Arm PR48 RGT BOC/PR48 % of Patients n=80 n=162 n=161 n=25 n=111 n=121 Bacon BR et al. N Engl J Med 2011;364:1207-1217.

  18. RESPOND-2: SVR by Response to Previous Peg-IFN/RBV Therapy According to Treatment Arm* PR 48 RGT BOC/PR48 RUGT SVR (%) 16/51 73/105 77/103 23/57 30/58 2/29 Bacon BR et al. N Engl J Med 2011;364:1207-1217.

  19. RESPOND-2: SVR According to Viral Load PR48 RGT BOC/PR48 RGT vs RUGT SVR (%) 6/15 12/15 16/20 11/65 83/147 91/141  Bacon BR et al. N Engl J Med 2011;364:1207-1217.

  20. Interferon Response

  21. SPRINT-2 and RESPOND-2: Evaluation of Predictive Value of PegIFN/RBV 4-week Lead-in Therapy Relationships Between Week 4 Lead-in and SVR Responsive to interferon ≥1.0 log10 viral load decline at treatment Week 4 Poorly responsive to interferon <1.0 log10 viral load decline at treatment Week 4 133/ 203/ 200/ 3/83 27/97 36/95 0/12 15/46 15/44 260 252 254 17/67 80/110 90/114 Vierling JM, et al. 46th EASL; Berlin, Germany; March 30-April 3, 2011: Abst. 481.

  22. IL 28 B

  23. SPRINT-2 ( Treatment Naïve): SVR by IL28B Polymorphism RGT vs RUGT % SVR 50 64 63 77 44 55 33 116 67 103 82 115 10 37 23 42 26 44 * * ~90% eligible for short duration therapy Poordad F, et al. EASL 2011, Abst..

  24. RESPOND-2( Treatment Experienced): SVR by IL28B Polymorphism RUGT % SVR 6 13 22 28 17 22 5 29 38 62 48 66 5 10 6 11 13 18 * * ~80% eligible for short duration therapy Poordad F, et al. EASL 2011, Abst..

  25. Easy to Treat Absence of fibrosis Low viral load Younger age Women IL 28 B CC Interferon sensitive Relapsers Difficult to Treat High viral load Obesity/Metabolic syndrome Blacks IL 28 B-C/T, T/T-Treatment Experienced Cirrhosis Older population Interferon insensitive Null and Partial Responders Response Unguided Therapy HCV Therapy:Candidates for Response Unguided Therapy

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