HCV disease: treatment or deferral? Antonio Craxì Gastroenterologia & Epatologia, Di.Bi.M.I.S., Università di Palermo

Transcription

1 HCV disease: treatment or deferral? Antonio Craxì Gastroenterologia & Epatologia, Di.Bi.M.I.S., Università di Palermo

2 Key factors in deciding to treat or wait Patient factors Urgency to treat Likelihood of response HCV genotype Treatment experience IL28B genotype Degree of fibrosis Patient motivation Treatment factors Efficacy of current options Safety of current options Duration of therapy Pill burden, dosing frequency Future options and their timelines

3 What will be the future? One Size Fits All? Same treatment regardless of fibrosis level, previous treatment experience, or HCV genotype?

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5 Problems with allocation to treatment Cost Overtreatment of some Simplicity One size fits all Cost Priorities Fewest drugs Tailored regimen for each population Shortest duration

6 HCV infection in Italy: who are we treating? Mild disease (chronic hepatitis F0-F1) Significant disease (chronic hepatitis F2-F3; Cirrhosis F4, Child A) Advanced disease (Cirrhosis, Child B-C, HCC, post-olt) P/R based regimens +/- boceprevir or telaprevir Knowledge of HCV carrier status

7 IFN free DAA will expand the pool of treatable patients Mild Severe Decomp HCV chronic disease spectrum Currently treated

8 2 nd generation DAAs: timeline to availability for clinical use (FDA EMA) IFN based regimen Sofosbuvir + P/R Gt1 Simeprevir+ P/R IFN free regimen Sofosbuvir IFN free Gt2 & 3 Daclatasvir ABT 450/R + ABT ABT 333 Sofosbuvir + ledipasvir Gt 1 Timeline assumes: -EMA approval 3 months after FDA approval - AIFA reimbursement granted 9 months after EMA approval Source: Internal assessment 2010 / 2011 MK5172+ MK8742?

9 2 nd generation DAAs: timeline to availability for clinical use in Italy (?) IFN based regimen Sofosbuvir + P/R Gt1 Simeprevir+ P/R IFN free regimen Sofosbuvir IFN free Gt2 & 3 Daclatasvir ABT 450/R + ABT ABT 333 Sofosbuvir+ ledipasvir Gt1 MK5172+ MK8742? Source: Internal assessment 2010 / 2011

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16 Treatment of HCV-1 in Italy: current status 7000 patients treated each year with a 10% yearly trend to decrease ¼ of HCV-1 patients were re-treatments: warehousing for triple therapy Yearly expenditure (2011) for dual therapy: 220,000,000 Aging population of naives (48 years) with 25-30% of F3/F4 At least 20,000 patients with previous P/R failures: usually unclassified, mean age > 55 years and 40% F3/F Gt 1 patients have received TT in 2013

17 Triple therapy regional access: main regions Region Regional Decree # Centres Centres accreditat ion Triple Therapy Estimate Start Estimate Triple Pts Pts. on treatment in Triple Lombardia Yes Feb Veneto Yes 9 8 Mar Emilia R. Yes 14 9 May Piemonte/VA Yes Feb Toscana Yes Mar Lazio Yes Feb Campania Yes Feb Puglia Yes May Sicilia Yes 12 8 June Other Regions ITALY * %BOC 54% TEL # Centers able to prescribe: 249/480 ( 52%) * Starting Therapy Pts; Full Year pts 28%with BOC 72% with TEL

18 Treat now or wait: issues to consider Treat now Defer Triple therapy increases SVR Earlier treatment has higher success rates Successful treatment may arrest progression of liver disease Uncertainty about timelines for approval and reimbursement of new DAAs First-generation PIs complex, associated with adverse events Potential for higher SVR, including difficult populations Potential for simpler regimens, QD or BID, fewer adverse effects, eventually IFN-free Activity in non genotype 1

19 Severity of Disease Increases Need for HCV Therapy but Also Impairs Response May not need immediate treatment BUT Easier to treat High likelihood of response Greater need for treatment BUT Response may be impaired Perhaps more effective options in future, but efficacy of some investigational agents may be unclear due to trial eligibility criteria Mild disease Advanced fibrosis/ cirrhosis

20 HCV infection in Italy: what patients are we aiming to cure? Mild disease (chronic hepatitis F0-F1) Significant disease (chronic hepatitis F2-F3; Cirrhosis F4, Child A) Advanced disease (Cirrhosis, Child B-C, HCC, post-olt) Cost effectiveness? IFN free DAAs +/- ribavirin Knowledge of HCV carrier status Screening

21 Global costs of HCV Gt1 therapy in naïves (assuming treatment of F2 to F4) Cost PegIFN/ RBV 48 wks BOC/TPV + P/R wks Sofosbuvir + P/R 12 wks Simeprevir + P/R 12 wks Sofosbuvir + RBV 24 wks Sofosbuvir+ simeprevir ± RBV 12 wks -drugs monitoring EPO, G-CSF, blood tx, others TOTAL Expected efficacy 40% 65% >90% >90% >90% >95% Eurosfor 1 SVR

22 Global costs of HCV Gt2 therapy in naïves (assuming treatment of F2 to F4) Cost -drugs -monitoring -EPO, G-CSF, blood tx, others TOTAL Expected efficacy Cost(Eu) for 1 cure PegIFN/RBV 24 wks % Sofosbuvir+ RBV 12 wks >90%

23 Dave Nelson, AASLD 2013

24 HCV patients: treatment decisions for 2014 Can be treatednowwith P/R (all naives): Expected SVR Urgency for cure Gt1, "easy to cure": F0 to F2 plus IL 28 cc or RVR after lead-in, no factors reducing IFN responsiveness(obesity, metabolic syndrome) >80% Modest Gt2 and 3, F3 to F4 Gt4, 5, 6, F3 to F4 50 to 70% Moderate to high 40 to 60% Moderate to high

25 HCV patients: treatment decisions for 2014 Can be treated nowwith P/R plus a 1 st generation PI (BOC or TPV): Expected SVR Need for cure NaiveGt1, "difficultto cure": F2 to F4 plus IL 28 non cc or no RVR afterlead-in, presenceof factorsreducingifn responsiveness(obesity, metabolic syndrome) AllGt1 relapsersto P/R, regardlessof stage Gt1 partialrespondersto P/R, F2 to F4 NaiveGt1 with HIV coinfection, F3 to F4 Gt1 with severe post-olt relapse (onlyifeap sofosbuvir+ DCV unobtainable) 50 to 65% Moderate to high 75 to 90% Modest to moderate 40 to 50% Moderate to high 50 to 70% High 30 to 50% Very high

26 HCV patients: treatment decisions for 2014 Shouldbe deferredfor new DAAs(+ P/R or IFN free; IFN free onlyfor F4 and OLT): Naive, allgenotypes, F0 to F1 Gt 1 null responders to P/R, F0 to F4 Gt1, failuresof triple therapywith P/R plus PI Gt 2 and 3, F0 to F4, naïvesand P/R failures Gt 4, 5, 6, F0 to F4, naïvesand P/R failures All decompensated patients All post OLT patients All patients with HIV coinfection Expected SVR Need for cure > 90% Modest > 90% Moderate to high > 90% Moderate to high > 90% Modest to high > 90% Modest to high??? Very high >70% Very high > 90% Very high

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