WHY CHOOSE TELAPREVIR Mitchell L Shiffman MD Liver

WHY CHOOSE TELAPREVIR Mitchell L Shiffman, MD Liver Institute of Virginia Bon Secours Health System Richmond and Newport News, VA, USA Liver Institute of Virginia IVer Education, Research and Treatment for Patients with Liver Disease Bon Secours Health System

TELAPREVIR TREATMENT NAÏVE AND RELAPSE HCV RNA UD RVR No RVR UD Telaprevir PEGINF Ribavirin UD PEGINF Ribavirin PEGINF-RBV Log HCV <3 <3 UD Stop Rule >3 >3 + Week 4 8 12 ML Shiffman, R Estaban Liver Intl 2012; 32 (suppl 1): 54 -60. 16 20 24 28 32 36 40 44 48 IVer

TELAPREVIR NON-RESPONSE AND CIRRHOSIS RVR HCV RNA No RVR Telaprevir PEGINF Ribavirin PEGINF-RBV Log HCV <3 <3 UD Stop Rule >3 >3 + Week 4 8 12 ML Shiffman, R Estaban Liver Intl 2012; 32 (suppl 1): 54 -60. 16 20 24 28 32 36 40 44 48 IVer

SVR RATES VERY COMPARABLE Boceprevir Telaprevir Treatment Naïve: e. RVR Delayed response % with e. RVR 96% 66 -75% 56% 89 -92% 64% 58 -60% Retreatment: Relapse Partial response Null response INF sensitive (lead-in) INF insensitive (lead-in) 69 -75% 40 -52% NA 73 -79% 33 -34% 84 -88% 56 -61% 31 -33% NA NA IVer

SVR RATES VERY COMPARABLE Boceprevir Telaprevir Treatment Naïve: e. RVR Delayed response % with e. RVR 96% 66 -75% 56% 89 -92% 64% 58 -60% Retreatment: Relapse Partial response Null response INF sensitive (lead-in) INF insensitive (lead-in) 69 -75% 40 -52% NA 73 -79% 33 -34% 84 -88% 56 -61% 31 -33% NA NA IVer

SVR RATES VERY COMPARABLE Boceprevir Telaprevir Treatment Naïve: e. RVR Delayed response % with e. RVR 96% 66 -75% 56% 89 -92% 64% 58 -60% Retreatment: Relapse Partial response Null response INF sensitive (lead-in) INF insensitive (lead-in) 69 -75% 40 -52% NA 73 -79% 33 -34% 84 -88% 56 -61% 31 -33% NA NA IVer

TELAPREVIR WHY CHOOSE THIS REGIMEN? It is just an easier treatment regimen IVer

TELAPREVIR ITS JUST EASIER • • All three medications are started at the same time All patients get 12 weeks of telaprevir • Treatment naïve • Prior relapse • Prior non-response • Cirrhosis IVer

TELAPREVIR ITS JUST EASIER • If you have to stop telaprevir at week 8 for adverse events the SVR is only marginally reduced. If e. RVR: PEGINF + Ribavirin Telaprevir PEGIFN-2 a Ribavirin If NO e. RVR: PEGINF + Ribavirin Telaprevir PEGIFN-2 a Ribavirin 0 8 Week of TPV 8 12 83% 89% 12 Weeks IM Jacobson et al. N Engl J Med 2011; 364: 2405 -16. 24 50% 54% 48 IVer

TELAPREVIR ITS JUST EASIER • • • Only 2 treatment durations Treatment naïve and prior relapsers: • 24 weeks if achieve extended rapid response • 48 weeks with delayed response Prior non-response and cirrhosis • 48 weeks IVer

TELAPREVIR ITS JUST EASIER • • • 60% achieve e. RVR. Treated for 24 weeks 21% have delayed response. Treated 48 weeks. 81% of patients become HCV RNA undetectable during treatment IVer

TELAPREVIR ITS JUST EASIER • • • Smaller pill burden 2 capsules TID = 6/day Randomized controlled trial suggests telaprevir can be dosed 3 capsules BID without impacting SVR P Marcellin et al. Gastroenterol 2011; 140: 459 -468. = IVer

TELAPREVIR ITS JUST EASIER • • • Stop rules at weeks 4 and 12. Allows resistant virus to be recognized earlier. Resistance monitoring uses the same cutt-off. • Week 4 >Log 3 • Week 12 >Log • Week 24 negative IVer

TELAPREVIR NEGATIVE FEATURES • • • Side effects of therapy Side effects of peginterferon and ribavirin Side effects of telaprevir • Anemia • Rash • GI symptoms IVer

RASH UNIQUE TO TELAPREVIR • • • Appears in over half of patients treated with telaprevir Typically appears during first 4 weeks of treatment Worsens progressively during treatment Most patients never reach stage 3 -4 If severe, can stop telaprevir a few weeks early The decline in SVR is minimal even in patients with delayed virologic response IVer

TELAPREVIR GRADE 2 RASH IVer

TELAPREVIR GRADE 3 RASH IVer

TELAPREVIR GRADE 4 RASH IVer

TELAPREVIR SIDE EFFCTS • GI toxicity: • Nausea • Vomiting • Diarrhea • Anal-rectal burning IVer

TELAPREVIR SUMMARY To treat HCV with Incevik Is not a trick. Just start it with PEG and Riba together. Treat for 12 weeks and see it get better. If negative at week 4. Its virtually a cure. Continue PEG and riba for sure. Till week 24. And then dash straight through the door. IVer

TELAPREVIR SUMMARY However, If the response is delayed. Do not be dismayed. For if less than a thousand by month 3. A cure can still be. Adhere to the stop rules at 4 and 12 weeks. This is important and so do not cheat. And you will see. This rule will keep you mutant free. IVer

TELAPREVIR SUMMARY AEs include rash, anemia and a sore bum. This is not fun. This make patients glum. And their physicians run. And so my friends, When treating with telaprevir there is no reason to quiver. Because its dam good at getting HCV Out of the liver. IVer