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HCV: Simplifying adapting diagnosis and therapy Dr. Isabelle Andrieux-Meyer MSF Access Campaign IAS Kuala Lumpur, Sunday 30 th June.

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Presentation on theme: "HCV: Simplifying adapting diagnosis and therapy Dr. Isabelle Andrieux-Meyer MSF Access Campaign IAS Kuala Lumpur, Sunday 30 th June."— Presentation transcript:

1 HCV: Simplifying adapting diagnosis and therapy Dr. Isabelle Andrieux-Meyer MSF Access Campaign IAS Kuala Lumpur, Sunday 30 th June.

2 Market opportunity How can we take advantage of the new diagnostics & treatment opportunities to create access to HCV diagnostics and treatment for people living in resource limited settings? How can we take advantage of the new diagnostics & treatment opportunities to create access to HCV diagnostics and treatment for people living in resource limited settings? MSF has performed an independent HCV landscape analysis to map current and future trends in disease burden, product development, and market evolution for diagnostics, and medicines used in HCV care. MSF has performed an independent HCV landscape analysis to map current and future trends in disease burden, product development, and market evolution for diagnostics, and medicines used in HCV care.

3 HCV: Simplifying adapting diagnosis and therapy Epidemiological data Epidemiological data HCV diagnosis landscape HCV diagnosis landscape HCV treatment landscape HCV treatment landscape

4 Epidemiological burden of HIV/HCV coinfection Worldwide between 150 and 170 million people live with hepatitis C infection. (WHO 2012) Worldwide between 150 and 170 million people live with hepatitis C infection. (WHO 2012) The majority of them are not aware of their infection. ( Lavanchy Liver Intl 2009) The majority of them are not aware of their infection. ( Lavanchy Liver Intl 2009) Between 4 and 5 million people living with HIV are currently co- infected with HCV.( Easterbrook Sem Liv Dis 2012) Between 4 and 5 million people living with HIV are currently co- infected with HCV.( Easterbrook Sem Liv Dis 2012) While HIV can be controlled by antiretroviral therapy, co- infected people die from HCV related complications, like liver cirrhosis or liver cancer. ( Nelson Lancet 2011). While HIV can be controlled by antiretroviral therapy, co- infected people die from HCV related complications, like liver cirrhosis or liver cancer. ( Nelson Lancet 2011). Chronic HCV infection is independently associated with a 50% increase in mortality among patients with a diagnosis of AIDS. ( Branch CID 2012) Chronic HCV infection is independently associated with a 50% increase in mortality among patients with a diagnosis of AIDS. ( Branch CID 2012)

5 New HCV /HIV epidemiological data. Center for Disease Analysis 2013 (1)

6 New HCV /HIV epidemiological data. Center for Disease Analysis 2013 (2)

7 HIV / AIDS TREATMENT PROGRAMMES MSF currently provides HIV treatment to 250,000 people in 23 countries.

8 MSF Access Campaign

9 HCV: Simplifying adapting diagnosis and therapy Epidemiological data Epidemiological data HCV diagnosis landscape HCV diagnosis landscape HCV treatment landscape HCV treatment landscape

10 Access to HCV testing: game -changer Globally, 59% of the world s population has no access to hepatitis C diagnosis. These findings correlate with the wealth of the country: Dx using serology is available in 53% of lower middle income countries, and 11% of low income countries ( WHA report 2010). These findings correlate with the wealth of the country: Dx using serology is available in 53% of lower middle income countries, and 11% of low income countries ( WHA report 2010). MSF RDT (rapid diagnostic test) procurement: HCV Scan (EY laboratories) HCV Scan (EY laboratories) HCV Spot (MP Medicals) HCV Spot (MP Medicals) Average price 1-4 EUR per test. Average price 1-4 EUR per test. New line OraQuick (Orasura, USA): Best and most up to date performance but 10-12x more expensive than other RDTs.( MSF HCV landscape analysis 2013) New line OraQuick (Orasura, USA): Best and most up to date performance but 10-12x more expensive than other RDTs.( MSF HCV landscape analysis 2013) => Limited evidence on the accuracy of HCV RDS in HIV/HCV coinfection. ( Shivkumar Ann Intern Med 2012)( Smith J Itl Dis 2011)

11 HCV confirmation test: Detection of HCV RNA Anti-HCV antibodies indicate exposure to the virus, but cannot determine if infection is present or if the infection has cleared spontaneously. Anti-HCV antibodies indicate exposure to the virus, but cannot determine if infection is present or if the infection has cleared spontaneously. All persons with positive anti-HCV antibody test must undergo additional testing for the presence of the HCV itself to determine whether current infection is present and whether there is an indication for treatment All persons with positive anti-HCV antibody test must undergo additional testing for the presence of the HCV itself to determine whether current infection is present and whether there is an indication for treatment 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 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. HCV PCR is hardly accessible and costs >=100 USD per test. We need affordable : We need affordable : POC HCV Viral load : pipeline Wave 80, Alere, Cepheid, IQuum, Daktari. 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) Flexible PCR platforms ( Multitest: HBV-HIV-HCV) like Sacace generic open platform test, or Qiagen. ( MSF HCV landscape analysis)

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13 Genotyping & Fibrosis evaluation The required length of peg-IFN-ribavirin treatment, the current standard of care, and the expected outcome from treatment, is dependent on the HCV genotype. The required length of peg-IFN-ribavirin treatment, the current standard of care, and the expected outcome from treatment, is dependent on the HCV genotype. Tests, using a range of different technologies: Tests, using a range of different technologies: Abbott, Roche, Siemens tests Abbott, Roche, Siemens tests Sacace: generic open platform test (real time PCR) Sacace: generic open platform test (real time PCR) Pipeline point-of-care test: Wave80 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 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) Liver fibrosis can be assessed at field level using Transient elastography: Fibroscan®, or serum biomarkers like APRI.(Lin ZH. Hepatol 2011)

14 HCV: Simplifying adapting diagnosis and therapy Epidemiological data Epidemiological data HCV diagnosis landscape HCV diagnosis landscape HCV treatment landscape HCV treatment landscape

15 PegIFN-Ribavirin Treatment Outcomes in LMICs very similar to high income settings Ford et al, Bull WHO 2012

16 Sustained virological response (SVR) in patients co-infected with HCV and HIV by disease, patient and treatment covariates. Sustained virological response (SVR) in patients co-infected with HCV and HIV by disease, patient and treatment covariates. Davies A, et al. PLoS ONE HCV genotypes 1 or 4 (pooled SVR 24.5%) vs genotypes 2 or 3 (pooled SVR 59.8%)

17 CHANGING HCV TREATMENT LANDSCAPE Dore GJ Med J Aust, 2012.

18 Novel drugs against HCV: DAA, HTA and their combinations IDX-320 Phase I Phase II Phase III Approved DAA: Nuc- Polymerase inhibitors DAA: Non Nuc- Polymerase inhibitors DAA: Protease inhibitors DAA: NS5A inhibitor HTA: Cyclophilin Inhibitors DAA combinations AZD07295 BMS BMS Telaprevir + VX-222 BMS BMS R ITMN-191 GS GS-9256 Boceprevir TMC435 ABT-450 MK5172 MK7009 (vaniprevir) Telaprevir BMS BI ACH1625 ITMN-191/R7227 GS-9190 ANA-598 VX-222 BI ABT IDX-184 R7128 PSI-7977 BI DAA = direct-acting antiviral HTA = host-targeting antiviral; Nuc = nucleos(t)ide SCY635 DEBIO-025 (Novartis) NOT EXHAUSTIVE BMS PSI-7792 BI BI IDX IDX-320 PSI PSI-938 VX-985 PF MK-0608 RG7348 TMC BMS ABT-072 ABT-333

19 HCV pipeline drugs (1) Several pharmaceutical companies are in a position to develop their own FDC. We need phase III trial results to confirm the positive preliminary results: Several pharmaceutical companies are in a position to develop their own FDC. We need phase III trial results to confirm the positive preliminary results: Gilead: SOFOSBUVIR based ( SOF-GS 5885-RBV) Gilead: SOFOSBUVIR based ( SOF-GS 5885-RBV) Sofosbuvir: FDA registration submitted April 10 th 2013 for GT1 ( IFN sparing) and for GT2 and 3 all oral. Sofosbuvir: FDA registration submitted April 10 th 2013 for GT1 ( IFN sparing) and for GT2 and 3 all oral. Sofosbuvir-Ledipasvir: Plan to submit 2014 Sofosbuvir-Ledipasvir: Plan to submit 2014 Abbott: ABT 450/r + ABT ABT RBV Abbott: ABT 450/r + ABT ABT RBV BMS: Daclatasvir- Asunaprevir based BMS: Daclatasvir- Asunaprevir based Boerhinger- Ingelheim: BI OD + BI /-RBV Boerhinger- Ingelheim: BI OD + BI /-RBV Janssen: Simeprevir Janssen: Simeprevir

20 Sofosbuvir ( ex- GS 7677) Gilead. Nucleoside/nucleotide polymerase inhibitor. Gilead. Nucleoside/nucleotide polymerase inhibitor. 400 mg once daily 400 mg once daily Phase III Phase III Potent, high genetic barrier to resistance Potent, high genetic barrier to resistance Pan genotype: GT 1,2,3,4,5,6. Pan genotype: GT 1,2,3,4,5,6. Simple, good safety and tolerability profile: common adverse events: fatigue, headache, nausea, insomnia, dizziness, no need of food intake, no significant drug interaction, no rash, less anemia. Simple, good safety and tolerability profile: common adverse events: fatigue, headache, nausea, insomnia, dizziness, no need of food intake, no significant drug interaction, no rash, less anemia. Under study in HIV-HCV co-infected people. Under study in HIV-HCV co-infected people. The initial indication in GT1,4,5,6 will be SOF + peg IFN/RBV for 12 to 24 weeks. The initial indication in GT1,4,5,6 will be SOF + peg IFN/RBV for 12 to 24 weeks. In GT 2 and 3 : SOF with or without RBV. In GT 2 and 3 : SOF with or without RBV.

21 Sofosbuvir in GT1 treatment naive Study name CombinationOutcomes ATOMIC 1 SOF+pIFN + RBV 12 or 24 weeks SVR 90% NEUTRINO 2 SOF + pIFN + RBV SVR 12: 89% ELECTRON 3 SOF+ Ledipasvir + RBV SVR 12 : 100% ( 34/34) ION-1 4 SOF+ Ledipasvir +/-RBV ongoing xxxxx 5 SOF+ Daclatasvir +/-RBV 12 or 24 weeks SVR 100% ELECTRON 6 SOF +RBV 12 weeks SVR4:88% QUANTUM 7 SOF +RBV 12 vs 24 weeks 12 weeks: SVR: 59% (10/17) SPARE 8 SOF +RBV (weight based or 600mg RBV) 12 weeks SVR12: 90%

22 Update Sofosbuvir EASL 2013 phase III StudyPopulation Treatment groups SVR12 rates Neutrino 910 GT 1/4/5/6 treatment-na ï ve treatment-na ï ve GT4:28 cases GT5:1case GT6:6 cases Sofosbuvir + RBV + Peg-IFN for 12 weeks 90% (295/327) GT 1a: 92% GT 1b: 82% Cirrhotic: 81% Fission 910 GT 2/3 treatment naive SOF + RBV for 12 weeks Or Peg IFN+RBV for 24 weeks 67% ( 107/253) GT2:97%GT3:56% 67% ( 162/243) Positron 910 GT2/3, IFN intolerant, ineligible or unwilling SOF+RBV for 12 weeks Or Placebo for 12 wks 78% ( 161/207) 0% (0/71) Fusion 910 GT2/3 treatment experienced SOF+RBV for 12 weeks Or SOF+RBV for 16 weeks 50% ( 50/100) GT2: 86% GT3: 30% GT3 non cirrhotics:37% GT3 cirrhotic: 19% 73% (69/95) GT2: 94% GT3: 62% GT3 non cirrhotic: 63%, cirrhotic: 61%

23 GS 5885= Ledipasvir Gilead. NS5a Inhibitor Gilead. NS5a Inhibitor In combination with Sofosbuvir and RBV for 12 weeks: SVR12 100% in GT1. In combination with Sofosbuvir and RBV for 12 weeks: SVR12 100% in GT1. Fixed dose combination Fixed dose combination In treatment experienced people: same protocol: SVR12: 100% In treatment experienced people: same protocol: SVR12: 100% SOF Ledipasvir registration expected SOF Ledipasvir registration expected Under study in HIV-HCV co-infected people. Under study in HIV-HCV co-infected people.

24 Daclatasvir (DCV) BMS. NS5a Inhibitor. BMS. NS5a Inhibitor. 60mg once daily 60mg once daily Phase III Phase III Potent, high genetic barrier to resistance Potent, high genetic barrier to resistance Genotype: 1,2,3,4. Genotype: 1,2,3,4. Simple, AE: fatigue, headache, nausea. No safety signal. Simple, AE: fatigue, headache, nausea. No safety signal. No data yet in HIV-HCV co-infected No data yet in HIV-HCV co-infected SVR: SVR: GT1 DCV +SOF +/-RBV 12 weeks: SVR12: 95% GT1 DCV +SOF +/-RBV 12 weeks: SVR12: 95% GT2 &3: DCV +SOF +/-RBV 12 weeks: SVR12: % GT2 &3: DCV +SOF +/-RBV 12 weeks: SVR12: % GT1 DCV +Asunaprevir +/-BMS or 24 weeks: SVR12: 94% GT1 DCV +Asunaprevir +/-BMS or 24 weeks: SVR12: 94% Studied with SOF, but collaboration stopped. Studied with SOF, but collaboration stopped. Limited data in liver advanced diseases, in HIV-HCV co-infected people and in treatment experienced people. Limited data in liver advanced diseases, in HIV-HCV co-infected people and in treatment experienced people.

25 ABT-450/ritonavir Abbott. Protease Inhibitor. Abbott. Protease Inhibitor. In Combination with ABT-267 +/-ABT-333 +/-RBV : In Combination with ABT-267 +/-ABT-333 +/-RBV : 100/100 mg, 200/100mg twice daily 100/100 mg, 200/100mg twice daily Phase III Phase III GT 1, under study in GT2 and GT3. GT 1, under study in GT2 and GT3. Potent, low genetic barrier to resistance Potent, low genetic barrier to resistance Genotype: 1. Under study in 2 and 3,no results yet. Genotype: 1. Under study in 2 and 3,no results yet. Simple, hyperbilirubinemia, fatigue, headache, pain, vomiting, some drug interaction expected, no safety signal. Simple, hyperbilirubinemia, fatigue, headache, pain, vomiting, some drug interaction expected, no safety signal. SVR : SVR : GT1 naïve: SVR12: 87-97% GT1 naïve: SVR12: 87-97% GT1 null responders: 87-93% GT1 null responders: 87-93% No data yet in HIV-HCV co-infected people, in treatment experienced people and in case of liver advanced disease. No data yet in HIV-HCV co-infected people, in treatment experienced people and in case of liver advanced disease.

26 SIMEPREVIR Janssen/Medivir/ Tibotec. Protease inhibitor. Janssen/Medivir/ Tibotec. Protease inhibitor. Phase III Phase III GT1and 4 GT1and 4 AE: flu-like symptoms, rash, neutropenia, transient elevation of bilirubin. AE: flu-like symptoms, rash, neutropenia, transient elevation of bilirubin. Can be interesting for treatment GT1 experienced people, or GT4 in addition to peg IFN RBV. Can be interesting for treatment GT1 experienced people, or GT4 in addition to peg IFN RBV. Under study with Daclatasvir and Sofosbuvir. Under study with Daclatasvir and Sofosbuvir.

27 Transformative Current Care Lab Requirements Lab Requirements Pre-treatment: Serology, VL, genotype, staging (ultrasound or markers), potential prognostic markers Pre-treatment: Serology, VL, genotype, staging (ultrasound or markers), potential prognostic markers Monitoring: 5 VL; CBC, Cr, ALT weeks 1,2,4 and monthly; TSH, T4 q3 month Monitoring: 5 VL; CBC, Cr, ALT weeks 1,2,4 and monthly; TSH, T4 q3 month Treatment Treatment (24-)48 weeks weekly injections, daily pills (24-)48 weeks weekly injections, daily pills High rates of side effects High rates of side effects Efficacy: about 50% Efficacy: about 50% Costs: Minimum $2500 Costs: Minimum $2500 The Future Lab Requirements Lab Requirements Pre-treatment: Serology, VL, genotype(?) Pre-treatment: Serology, VL, genotype(?) Monitoring: 3 VL, Monthly Creat/Hg/ALT Monitoring: 3 VL, Monthly Creat/Hg/ALT Treatment Treatment weeks 2 pills daily weeks 2 pills daily Efficacy: % Efficacy: % Costs: oral regimen should be < 500 USD per diagnostic +treatment package Costs: oral regimen should be < 500 USD per diagnostic +treatment package

28 Key programmatic components for provision of HCV treatment An adequate clinic infrastructure An adequate clinic infrastructure Laboratory and diagnostic services Laboratory and diagnostic services Drug Supply Drug Supply Human Resources (doctors,nurses and psychosocial support) Human Resources (doctors,nurses and psychosocial support) Referral system Referral system Monitoring and Evaluation Monitoring and Evaluation Civil society participation Civil society participation

29 Conclusion More data are needed for people living with HIV-HCV co-infection, and advanced liver disease. More data are needed for people living with HIV-HCV co-infection, and advanced liver disease. Simplified diagnosis procedures and 2nd generation DAA treatment regimen will substantially increase impact and feasibility of treatment, and treatment as prevention ( Gane E, NEJM 2013, Poordad F, NEJM 2013) Simplified diagnosis procedures and 2nd generation DAA treatment regimen will substantially increase impact and feasibility of treatment, and treatment as prevention ( Gane E, NEJM 2013, Poordad F, NEJM 2013) Enhanced efficacy (likely >90% all genotypes) Enhanced efficacy (likely >90% all genotypes) Once/twice-daily oral-only dosing Once/twice-daily oral-only dosing Reduced toxicity Reduced toxicity High barrier to resistance High barrier to resistance Shortened treatment duration (~12 weeks) Shortened treatment duration (~12 weeks) May lead to: May lead to: Higher uptake/adherence/completion Higher uptake/adherence/completion Integration, decentralization and scaling –up of HIV-HCV services, including vulnerable groups like injection drug users. Integration, decentralization and scaling –up of HIV-HCV services, including vulnerable groups like injection drug users. If the package of diagnosis and treatment can be largely available at affordable cost : < 500 usd. If the package of diagnosis and treatment can be largely available at affordable cost : < 500 usd.

30 MSF new report: /content/diagnosis- and-treatment -hepatitis-c- technical-landscape

31 Acknowledgments MSF viral hepatitis team: MSF viral hepatitis team: D.Donchuk, H.Bygrave, Marcio Fonseca da Silveira, M.Serafini, P.Du Cros, S.Balkan. D.Donchuk, H.Bygrave, Marcio Fonseca da Silveira, M.Serafini, P.Du Cros, S.Balkan. MSF hepatitis access team: MSF hepatitis access team: J.Cohn, T.Roberts, M.Balasegaram,R.Malpani, B.Milani, A.Rehman, K.Athersuch, N.Ernoult, L.Menghaney, P.Cawthorne, J.Rius. J.Cohn, T.Roberts, M.Balasegaram,R.Malpani, B.Milani, A.Rehman, K.Athersuch, N.Ernoult, L.Menghaney, P.Cawthorne, J.Rius. Questions: Questions:


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