Scaling up screening, diagnostic and treatments for people living with HCV in 2014?

Transcription

1 Scaling up screening, diagnostic and treatments for people living with HCV in 2014? Isabelle Andrieux-Meyer, MD Médecins Sans Frontières Access Campaign WHO Technical Briefing Seminar November 6 th,2014 Isabelle.andrieux-meyer@geneva.msf.org

2 Scaling up screening and diagnostics for people living with HCV - Access to reliable epidemiological data - Access to HCV screening & diagnostic - Who is the most at risk? - Access to HCV treatments in 2014 in LMIC?

3 Global Prevalence of Hepatitis C

4 New HCV /HIV epidemiological data. Center for Disease Analysis 2013

5 Access to HCV screening: a game changer Globally, 59% of the world s population has no access to hepatitis C diagnosis. Dx using serology is available in 53% of lower middle income countries, and 11% of low income countries ( WHA report 2010). HCV Scan (EY laboratories) sensibility: 100%, specificity: 93.7% ( WHO 2001) or HCV Spot (MP Medicals) : average price 1-4 eur per test MSF recommends OraQuick (Orasure, USA): Best and most up to date performance but 10-12x more expensive than other RDTs.( 14 euros/test) (sensibility: 99.2%, specificity: 99.8% ( Lee 2010) Can be done onwholeblood(e.gfingerprick)ororalfluid. (MSFHCVlandscapeanalysis2014) Limited evidence on the accuracy of HCV RDTs in HIV/HCV coinfection. ( ShivkumarAnnInternMed2012)( SmithJItlDis2011)

6 Primary prevention /HCV transmission Blood to blood contact. Transmission in developed countries: 90% chronic HCV infection were infected through transfusion of unscreened blood ( Alter JAMA 1990) Or sharing contaminated needles or other drug injection equipment ( Villano SA, Drug and Alcohol Dependance 2009).HCV seroprevalence among drug users(idu):60%(nelsonpk,lancet2011) Less commonly HCV is transmitted by sexual contact with an infected person, including MSM, or birth to an infected mother.( Wandeler G CID 2013) In developing countries: the primary sources of HCV infection are unsterilized injection equipment and infusion of inadequately screened blood and blood product.

7 MSF UNITAID HIV-HCV grant HCV public health problem, prevalence HCV HIV co-infection 52.3% HCV-HIV co-infected patients in NE India (Devi KS,I nis,2005) 67.2%inIDUinIran (SeyedAlinaghiS,ActaMedIran2011) 10.3% in Nairobi, Kenya (Muriuki BM, BMC Research notes 2013) 15.7% in Mozambique( Rodrigues, 2008) 29%inNorthMyanmar (MSFOCA2014,unpublisheddata) 53.3%amongIDUinUkraine (MSFOCB,unpublisheddata)

8 Who is the most at risk?preliminary investigation India: transgender people, people using drugs (IDU), commercial sex workers( CSW) Myanmar: Migrants, IDU Ukraine: prisoners, complex HIV patients, MDRTB, TB patients,menwhohavesexwithmen(msm) Iran: commercial sex workers, IDU Mozambique &Kenya: IDU, CSW?, blood recipient, invasive medical dental surgical procedure, tatoos, health care workers, prisoners, mobile populations ( migrant workers, miners) Need to investigate patterns of transmission at country level, collect epidemiological datas

9

10 HCV confirmation test: Detection of HCV RNA HCV PCR is the most common method to detect viral RNA. It is also used to quantify the virus for treatment monitoring purpose. Usually: Abbott, Roche, Siemens quantitative VL. HCV PCR is hardly accessible and costs >=100 USD per test. We need affordable : POC HCV Viral load : pipeline Wave 80, Alere, Cepheid, IQuum, Daktari. Flexible PCR platforms ( Multitest: HBV-HIV-HCV) like Sacace generic open platform test, or Qiagen. ( MSF HCV landscape analysis 2014) Prohibitive Costs: Georgia: serology+ PCR RNA HCV+ genotype=usd135 Nigeria, India: package=500 USD

11 3. Genotyping & Fibrosis evaluation The required length of peg-ifn-ribavirin treatment, or oral treatments, and the expected outcome from treatment, is dependent on the HCV genotype. Tests, using a range of different technologies: Abbott, Roche, Siemens tests Sacace: generic open platform test (real time PCR) Pipeline point-of-care test: Wave80 New oral drugs will allow for simplification, if we have access to pan-genotypic treatment then genotyping may not be needed Liver fibrosis can be assessed at field level using Transient elastography: Fibroscan, or serum biomarkers like APRI( Lin ZH. Hepatol 2011) ( WHO HCV Guidelines 2014).

12

13 Treatment should be simple, highly effective, pan-genotypic, potent, at affordable cost, easy to take ( MSF HCV landscape analysis 2014) Drug /combination Overall Results Sofosbuvir (SOF) ribavirin ( RBV) GT2, phase III 12weeks SVR12: 93% SOF RBV GT3, phase III 24 weeks SVR12: 85% SOF RBV GT1 phase III 24 weeks SVR12: 76% Peg-IFN +SOF+RBV GT1 phase III 12 weeks SVR12: 90% SOF + LDV(ledipasvir) GT1 phase III 12 weeks SVR % SOF+LDV GT1 phase III 8 weeks SVR12: 94% SOF+ LDV+GS 9669 GT1 phase II 6 weeks SVR12 95% ( N=20) SOF+LDV+GS 9451 GT1 phase II 6 weeks SVR12 100% ( N= 20)

14 Drug/combination Overall 3. Update results EASL 2014 Sofosbuvir+ GS weeks (Everson EASL 2014) Sofosbuvir+ledipasvir HIV+HCV, N=50 ( Osinusi A.EASL 2014) SOF 400mg+GS mg N= 77 GT1: SVR12 28/28 :100% GT2: 10/10 : 100% GT3: 25/27 : 93% GT4: 7/7 GT5: -- Gt6: 5/5 GT1 no ART: SVR12: 10/10 GT1 on ART: SVR4: 21/21 SOF 400mg+GS mg N=77 GT1 : SVR12: 26/27 : 96% GT2: 10/11 : 91% GT3: 25/27: 93% GT4: 6/7 GT5: 1/1 Gt6: 4/4 Sofosbuvir ledipasvir 400/90 mg Electron 2 ( EASL 2014 oral6) GT3 12 weeks SOF+LDP+RBV : SVR12: 19/19 ( 100%) GT3 12 weeks SOF+LDP: SVR12: 16/26 ( 64%) Sofosbuvir ledipasvir Electron 2 ( EASL 2014 oral6) GT1 prior failure peg IFN +RBV: SOF+LDP+RBV: SVR12: 19/19 GT1 decompensated cirrhosis or Child B: SOF+LDP no RBV: SVR12: 13/20 well tolerated

15 LDV/SOF STR Study* regimen SVR12 ION-1(n=865) GT1 naive 16% cirrhosis ION-2 (n=440) GT1 experienced 20% cirrhosis ION-3 (n=647) GT1 naive no cirrhosis LDV/SOF STR 12 weeks 99% 94% LDV/SOF STR 12 weeks LDV/SOF 8 weeks 94% 94% Adding ribavirin did not increase SVR12 LDV/SOF STR was safe and well tolerated Addition of RBV contributed to higher incidence of AE and lab abnormalities, including mean hemoglobin levles over time. ION-1 and 2: 24 weeks results are similar to 12 weeks results ION-3: 8 weeks and 12 weeks results are similar

16 The best components should be studied in combination and selected for market impact (MSF HCV landscape analysis 2014) Drug /combination SOF+simeprevir SOF+simeprevir + RBV SOF+Daclatasvir (DCV) SOF+DCV+RBV Overall results GT 1phase II 12 weeks SVR12 100% (n=14) SVR12 100% (n=12 GT1 phase II 12 or 24 weeks SVR12 100% ( n=14) SVR12 95% ( n=15) SOF +DCV GT1 Naïve SVR12 98% GT1 Experienced SVR12 98% SOF+DCV SOF+DCV DCV+ asunepravir+ BMS DCV 30mg+ simeprevir (SMV)+/- RBV ABT 450/ +-ABT ABT333+-RBV GT2 SVR12 92% (n=26) GT3 SVR12 89% (n=18) GT1 phase II -12 or 24 weeks SVR12 94% GT1 SVR12= 75-85% in treatment naïve SVR 12 = 65-95% in prior null responders phase III, GT1, tt naïve, 12 weeks: 3 DAA+ RBV : SVR12: 99.5%,3 DAA: SVR12: 99%

17 Merck pipeline Phase 1b Phase 2 Phase 3 Reg review MK-3682 ( NS5b PI) Ex Idenix MK-8408 (NS5a I) MK-1894 ( NS5a I) Samatasvir MK-5172 ( NS3/4 PI) MK-8742 ( NS5a I) Vamiprevir ( Japan) (NS3/4Pi)

18 Daclatasvir: European Commission Approval August 2014 (1) GT 1 or 4 no cirrhosis Daclatasvir (Daklinza)sofosbuvir GT1 or 4 compensated cirrhosis 12 weeks, consider prolongation to 24 weeks with prior treatment including NS3a/4 protease inhibitor Daclatasvir sofosbuvir Shortening treatment to 12 weeks may be considered for patients previously untreated with cirrhosis and positive prognosis factors such as IL28B CC genotype and /or low baseline viral load Consider add ribavirin with patients with very advanced liver disease or with negative prognosis factor such as prior treatment experience

19 Daclatasvir approval (2) GT 3 with compensated cirrhosisand/or treatment experienced GT4 Daclatasvir sofosbuvir ribavirin Daklinza peginterferon ribavirin 24 weeks 24 weeksdaclatasvirin combinationwith24-48 weks of peginterferon ribavirin.

20 Daclatasvir access issues Voluntary licensing program for 90 countries has been announced last Friday Tiered pricing strategy No commitment on registration Concerns about market diversion

21 Basic regimen: Specific drug requirements for MSF projects GT1,3,4: SOF RBV, 24weeks GT2: SOF RBV,12 weeks GT5, 6: pegifn SOF RBV 12 weeks - Compatible with Atripla, no data/ nevirapine and lopinavir based regimen. Alternatives needed for : Intolerants to ribavirin ( anemia) Advanced liver disease Sofosbuvir ledipasvir, no need RBV, Gt1,2,3 Or Sofosbuvir daclatasvir combinations w/wo RBV (pan GT)

22 Sovaldi : USD for 12 weeks USA, euros for 12 weeks in France France, 1700 dollars in Egypt.

23 Gilead Access program : 60 countries belong to the lowest tiered pricing category, price negotiations for sofosbuvir s price start at USD per bottle of 28 tablets USD for 12 weeks. ( Gilead PR, February 2014) If you need to buy peginterferon: Merck: negotiate the Egyptian price: 40 USD per vial, including ribavirin! If you need to buy ribavirin to combine to sofosbuvir: Zydus: minimal quantity 750,000 caps, price per caps: 0.30 USD.

24 COST PER PERSON, FOR12 WEEK COURSE OFHCV DAA Agent Daily Dose (mg) Overall dose for 12wks (g) Production cost estimate ($/g) Predicted cost ($) Ribavirin * 50** Daclatasvir Sofosbuvir MK MK Ledipasvir * current mid-point cost of API from 3 Chinese suppliers **shows cost for 1200mg daily dose; $41 for 1000mg daily dose of ribavirin Courtesy Andrew Hill. Poster LBPE12. IAC 2014.

25 BUNDLEOFCARE COSTS-A. HILL-

26 Interventions to overcome access barriers to HCV treatment Access to reliable epidemiological data, investigation of the patterns of transmission. Access to reliable and affordable diagnostics ( WHO pre-qualified, rapid diagnostic tests, multi-analytic PCR platforms, Point of Care HCV viral load). Access to care without discrimination, including people who use drugs. Demonstration projects: performance & feasibility at large scale, simplification, task shifting, training, including screeningprevention-harm reduction-treatment in different epidemiological contexts. Free generic competition Goal: diagnostic treatment package< 500 USD per cure.