Translating clinical trial promise into real world HCV treatment success. Dr K Agarwal Kings College Hospital London

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1 Translating clinical trial promise into real world HCV treatment success Dr K Agarwal Kings College Hospital London

2 Disclosures: BoJo Pharma support: AbbVie/Achillion/ Astellas/ BI/ BMS/ Gilead/ GSK/ Intercept/Janssen/ Merck/ Novartis/ Roche Spectrum in audience I will take the Why not viewpoint I am fascinated by your election!

3 A moderated discussion?

4 Areas of discussion with a European flavour The drugs work! Do niche populations exist - expectation The size of the problem? Cost and access issues Policy makers and traction System delivery issues Who is doing it well? What s the end game? eradication / elimination Disruptive technologies micro RNA, vaccine NB Yoda the future is always in motion

5 Treatment outcomes with 8-, 12- and 24-week regimens of SOF/LDV: Analysis of a multicenter prospective, observational study TARGET Registry: Pts treated according to local standards of care at academic (n=44) and community medical centers (n=17) in North America and Europe: N=2321 started Tx, virologic outcome known for % male, mean age 60 yrs, 20% black, 65% G1a, 27% G1b; 53% TN 38% cirrhotics (13% decomp), 3% HIV coinfection, 10% had received LT Pts who received RBV more likely to be Tx-experienced (69%), have cirrhosis (63%), have received LT (44%) SVR, by regimen SVR, by use of proton pump inhibitor (PPI) at Regimen SVR12, n/n (%) SOF/LDV 8 wks 150/154 (97) SOF/LDV 12 wks 607/627 (97) SOF/LDV 24 wks 153/161 (95) SOF/LDV 12 wks + RBV 86/89 (97) SOF/LDV 24 wks + RBV 12/13 (92) SVR12 (%) BL 323 pts qualified for 8-wk Tx duration, of these wk, wk: SVR 97% for both Tx durations Safety: SAEs reported in 114/2321 of all pts who started therapy (5%) AEs reported in 65% of pts (headache 24%, fatigue 22%, nausea 8%, diarrhea 7%, insomnia 7%) SOF/LDV-containing 8 and 12-wk treatment regimens are generally safe, well tolerated, and highly effective across a broad spectrum of patients and clinical practices 8-week regimen underutilized Overall SVR rates high, although PPI use associated with higher rate of VF 122/ / / 464 Terrault N, et al. AASLD 2015, San Francisco. #94 151/ 163

6 SVR12 (%) Real-World Cohorts at AASLD Support Clinical Trial Data GT 1: LDV/SOF 8 weeks 97% 95% 97% 100% 99% Phase 3 Studies TRIO Cohort HCV- TARGET 97% (638/658) overall SVR for LDV/SOF 8 weeks IFI GECCO Kowdley KV, et al. N Engl J Med 2014;370: ; Curry M, et al AASLD 2015; Terrault N, et al AASLD 2015; Buggisch P, et al. AASLD 2015; Christensen, et al. AASLD 2015;

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9 Diagnosis & Education remain critical Show me the numbers Mrs Landingham, that s how you win the argument and convince me, Show me the numbers J Bartlett West Wing

10 HCV-associated complications will increase markedly over the next 5 10 years Germany France Spain England Razavi et al., J of Viral Hepatitis 2014 HCC, hepatocellular carcinoma. Razavi H, et al. J Viral Hepat 2014;21(Suppl. 1):34 59.

11 Lancet 2015 Lifestyle = Liver = silent

12 Don t believe everything you read in the BMJ

13 Who is best placed to treat? Location? Outcomes of Treatment for Hepatitis C Virus Infection by Primary Care Providers Sanjeev Arora, M.D., Karla Thornton, M.D., Glen Murata, M.D., Paulina Deming, Pharm.D., Summers Kalishman, Ph.D., Denise Dion, Ph.D., Brooke Parish, M.D., Thomas Burke, B.S., Wesley Pak, M.B.A., Jeffrey Dunkelberg, M.D., Martin Kistin, M.D., John Brown, M.A., Steven Jenkusky, M.D., Miriam Komaromy, M.D., and Clifford Qualls, Ph.D. The results of this study show that the ECHO model is an effective way to treat HCV infection in underserved communities. Implementation of this model would allow other states and nations to treat a greater number of patients infected with HCV than they are currently able to treat. N Engl J Med Volume 364(23): June 9, 2011

14 New players such as Zepatier

15 Approaches to HCV Clinical approach Individual management CURE Primary prevention Early Detection Clinical management Follow up Ticketing? Rx Shouldn t Rx be a right? R Benjoa

16 Approaches to HCV Comprehensive approach Population management CURE Primary prevention Early Detection Clinical management Follow up Awareness Screening Surveillance Risk group Harm reduction Access/ Diagnostics Rx Standards of care Training Outcomes Pathways Package

17 Outcome Strategic Map for Hepatitis C Services Reduction in premature mortality from liver disease Reduction in Mortality for people with Hepatitis C Outcomes Improvement Drivers Strategy Stakeholders Improvement Opportunities Reduction in Health Inequalities Reduction in Liver cancer and transplantation Reduction in decompensated cirrhosis and hospital admissions Increase in public awareness Increase in Prevention Needle exchange services Drug enforcement Increase in screening and testing of Hep C to improve early diagnosis Social marketing campaign for key messages of hepatitis C Education of patients and carers Education of Health Professionals in primary and secondary care Treatment for active injectors with hepatitis C infection Liver function testing in PC Hep C in Prison Health Services Pharmacy testing Screening and testing of new immigrants Nursing competencies NICE Guidance - TA 106, TA 200, TA 75, PH 18 Increase in the treatment and management of Patients with Hepatitis C MDT treatment service based In secondary care Case finding and timely referral in Primary Care Outreach point of care testing Hepatitis C prominent in Alcohol, homelessness, obesity, and sexual health services and other high risk behaviours National Liver Strategy and Hepatitis C Action Plan Diagnostic services Community outreach Treatment service Transplantation services Primary, secondary and tertiary care, CCG, HWBB, NCB, HCV Action, Police, LA, LPC, Networks (formal/informal), Patient groups

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19 Danish model

20 Number of incident liver failures Prevalence(%) Modelled number of: (A) incident liver failures among persons with chronic HCV infection, and (B) prevalence of chronic HCV infection among persons actively injecting drugs, in Scotland, , according to treatment strategy (A) Treating patients per annum Post interferon-free strategy applied (B) Treating patients per annum Post interferon-free strategy applied YEAR YEAR Strategy-1 (treat 2,000 per annum; maintain status quo patient composition) Strategy-2 (treat 2,000 per annum; treat a greater proportion of active injectors) Strategy-3 (treat 2,000 per annum; treat a greater proportion of patients with moderate/advanced fibrosis). Prof. David Goldberg. February 2014

21 I like thinking big If you re going to think anything, you might as well think big D Trump