Interferon free therapy Are we getting there? Graham R Foster Queen Marys University of London

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1 Interferon free therapy Are we getting there? Graham R Foster Queen Marys University of London

2 IFN free therapy Disclosures I have received personal and institutional funding from companies that sell drug to treat hepatitis C including Roche, Novartis, Janssen, Gilead, Merck, BI, BMS and GSK

3 IFN free therapy IFN free therapy means ALL patients are going to receive IFN free treatment We are a long way from this

4 Clinical Trials Clinical trials are designed to show a drug at its best

5 Clinical Trials How many trials have you seen in: Patients with portal hypertension Patients with immunosuppression Injection drug users

6 Clinical Trials How many trials have you seen in: Patients with portal hypertension Patients with immunosuppression Injection drug users People who are likely to fail

7 Clinical Trials Clinical trials show a drug at its best...

8 GS RBV in Genotype 1 HCV GS mg QD + RBV SVR4 (%) n=25 n=19 n=19 n= New Zealand Cirrhotics excluded 56% non CC USA Cirrhotics (fibrosis stage 2) not excluded 84% non CC USA Mainly African Americans RBV, ribavirin; SVR4, sustained virological response at 4 weeks; TN, treatment naïve; QD, once daily 1. EASL, Barcelona, Spain, April 2012; Abstract 1113; 2. Press release, Gilead Sciences, 19 July 2012

9 Daclatasvir + GS 7977 ± RBV in Tx Naive GT1, 2/3 Pts Wk 1 Wk 24 Wk 48 Treatment naive patients with GT1a or 1b HCV infection (n = 44) A B C GS 7977 (n = 15) Daclatasvir + GS 7977 Daclatasvir + GS 7977 (n = 14) Daclatasvir + GS Ribavirin (n = 15) Follow up Follow up Follow up Treatment naive patients with GT2 or 3 HCV infection (n = 44) D E F GS 7977 (n = 16) Daclatasvir + GS 7977 Daclatasvir + GS 7977 (n = 14) Daclatasvir + GS Ribavirin (n = 14) Follow up Follow up Follow up GS 7977 dosed 400 mg QD. Daclatasvir dosed 60 mg QD. RBV dosed by body weight for GT1 pts ( mg/day); 800 mg/day for GT 2/3 pts. Sulkowski M, et al. EASL Abstract 1422.

10 Daclatasvir + GS 7977 ± RBV: Efficacy Analysis According to Genotype Genotype 1a/1b HCV Genotype 2/3 HCV Patients (%) n = Wk 4 Wk 24 (EOT) SVR4 Group A Group B Group C Light: < LOD Dark: < LLOQ and detectable Patients (%) n = * Wk 4 Wk 24 (EOT) SVR4 Group D Group E Group F Light: < LOD Dark: < LLOQ and detectable mitt analysis, bars not reaching 100% after Wk 4 reflect missing values. mitt analysis, bars not reaching 100% after Wk 4 reflect missing values. *1 patient required addition of pegifn alfa/rbv (tx intensification), 1 patient with relapse at posttreatment Wk 4 2 patients lost to follow up (following Wk 12 and 24 visits). Sulkowski M, et al. EASL Abstract 1422.

11 Co Pilot: 12 Wk ABT 450/r + ABT RBV in Tx Naive and Exp d GT1 Patients Interim analysis of nonrandomized, prospective, open label phase II trial Wk 12 Treatment naive patients infected with genotype 1 HCV (n = 33) Treatment experienced* patients infected with genotype 1 HCV (n = 17) ABT 450/Ritonavir 250/100 mg QD + ABT mg BID + RBV mg QD (n = 19) ABT 450/Ritonavir 150/100 mg QD + ABT mg BID + RBV mg QD (n = 14) ABT 450/Ritonavir 150/100 mg QD + ABT mg BID + RBV mg QD (n = 17) 48 wks of follow up *Previous null response (< 2 log 10 decrease in HCV RNA by Wk 12) or partial response (HCV RNA above limit of detection during treatment) Poordad F, et al. EASL Abstract 1399.

12 Co Pilot: Virologic Outcomes SVR12 in 94% of treatment naive and 47% of treatment experienced patients Responses independent of IL28B genotype RVR ervr SVR4 SVR12 Patients (%) ABT 450/r 250/100 mg QD + ABT RBV Treatment naive (n = 19) ABT 450/r 150/100 mg QD + ABT RBV Treatment naive (n = 14) ABT 450/r 150/100 mg QD + ABT RBV Nonresponders (n = 17) Poordad F, et al. EASL Abstract 1399.

13 Interferon Free Trials Encouraging results BUT

14 Interferon Free Trials Encouraging results BUT Easy to treat populations Motivated, closely monitored patients

15 Interferon Free How will these drugs work in the real world? Compliance PegIFN has a long half life Ribavirin lasts for ever A few missed doses does not matter

16 Cumulative ribavirin exposure week after full exposure week 1 12: SVR n=325 ETR SVR >97% >80 97% >60 80% 0 60 % Cumulative Ribavirin Exposure P= Reddy KR et al Clin Gastroenterol Hepatol 2007

17 Compliance with new drugs Unstudied Unknown (How many of your HBV patients are fully compliant?)

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19 Costs The new drugs won t be cheap Everyone is broke

20 Costs 2015 choice of therapy PegIFN + Riba G2/3 non cirrhotic E6,000 Oral combo G2/3 non cirrhotic E30,000 PegIFN + Riba G1 IL 28 CC E6,000 Oral combo G1 IL 28 CC E60,000

21 Costs The new drugs won t be cheap Everyone is broke Who will pay for the new drugs?

22 Madame Sosotris, famous clairvoyant

23 HCV patients cheap oral drugs Everyone gets IFN free Failures (20%) go on to IFN plus regimes

24 HCV patients expensive oral drugs Poor people with easy to cure disease IFN REGIMES Rich people with easy to cure disease ALL ORAL REGIMES Poor people with challenging disease Viral specific therapy

25 All Oral Therapy for HCV Are we nearly there? Success with IFN free regimes depends upon: Virological success Economic success Successful delivery

26 All Oral Therapy for HCV Are we nearly there? Success with IFN free regimes depends upon: Virological success Economic success Successful delivery (easy cases)

27 IFN free regimes Are we nearly there? NO