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New Treatment for HCV G4 Towards an End to HCV Epidemic in Egypt

New Treatment for HCV G4 Towards an End to HCV Epidemic in Egypt. Several potential innovative drug targets in HCV. NS3. NS2. NS5A. c. NS5B. E1. E2.

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New Treatment for HCV G4 Towards an End to HCV Epidemic in Egypt

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  1. New Treatment for HCV G4 Towards an End to HCV Epidemic in Egypt

  2. Several potential innovative drug targets in HCV NS3 NS2 NS5A c NS5B E1 E2 1. Rehman S, et al. Genet Vaccines Ther 2011;9:11. 2. http://clinicaltrials.gov/ct2/show/NCT01464827. 3. http://ir.achillion.com/releasedetail.cfm?releaseid=6989383. 4. Gish R & Meanwell NA. Clin Liver Dis 2011;15:627–39. 5. Coelmont L, et al. PLoS One 2010;5:e13678. 6. http://clinicaltrials.gov/ct2/show/NCT01448200. 7. Miller DM, et al. Ann N Y Acad Sci 2009;1182:807. 8. http://clinicaltrials.gov/show/NCT01309932. 9.Poordad F, et al. AASLD 2012, abstract 83. 10. Gane E, et al. EASL 2012, poster 1113. 11. http://clinicaltrials.gov/ct2/show/NCT01030432. 12 . Delang L, et al. Viruses 2010;2:826–66. 13. http://www.gilead.com/research. 14. http://clinicaltrials.gov/ct2/show/NCT01353911. 15. Wedemeyer H, et al. Hepatology 2013 January 24. [Epub ahead of print]. doi: 10.1002/hep.26274. 16. http://www.pipelinereport.org/browse/hcv-treatment/bi-207127. 17. http://www.pipelinereport.org/browse/hcv-treatment/abt-072. 18. http://clinicaltrials.gov/show/NCT01193361. 19. http://www.vrtx.com/research-development/pipeline. 20. http://news.bms.com/press-release/financial-news/bristol-myers-squibbpresent-new-data-hepatitis-c-and-hepatitis-b-compo. [Accessed April 10, 2013]. *On clinical hold, Novartis press release

  3. Characteristics of DAA Average profile Least favorable profile Good profile Schinazi, et al. Liver Int 2014;34 Suppl 1:69-78

  4. Many studies have looked at different ways of combining these compounds NS5A In different patient types NS5A NS3/4A RBV Alfa RBV Alfa • Different genotypes • Treatment-naive • Null-responders to prior therapy • Intolerant to previous therapy NS3/4A Alfa Lambda RBV Lambda NS5A RBV RBV NS5A NS3/4A NS5B (nuc inhibitor) NS5B (non-nuc inhibitor) RBV NS5A Lambda NS3/4A NS3/4A RBV Alfa, peginterferon alfa-2a; lambda, peginterferon lambda-1a; RBV, ribavirin This slide represents just a small selection of studies and regimens in current clinical development – other combinations are therefore possible

  5. Sofo+RBV

  6. Sofo+IFN+RBV

  7. Sofo and other DAA combination trials • Gane (2013), Hepatology 2) Lawitz (2013), Lance, 3) Jacobson (2013), Hepatology

  8. SOF + RBV: In genotype 4 This study done on 60 Egyptians (G4) living in USA 20% of them are cirrhotics. SVR12 (%) 13/15 14/14 11/14 10/17 27/29 21/31 12 WeekSOF + RBV 24 WeekSOF + RBV 12 WeekSOF + RBV 24 WeekSOF + RBV 12 WeekSOF + RBV 24 WeekSOF + RBV Treatment experienced Treatment naïve All Ruane PJ, et al. EASL 2014. P1243 Ruane PJ, et al. EASL 2014. P1243 Ruane PJ, et al. AASLD 2013. Abstract 1090

  9. Sofosbuvir+ Ribavirin in G4 (Egypt) (Esmat, et al AASLD.2014)

  10. In 51 patients GT4, received SOF + RBV for 12 weeks, SVR in 39 (77%) • Pts who were treatment naïve, Fibrosis stage<F3, and baseline viremia <600,000 IU were 9 pts. All showed SVR (100%) • Pts who were either treatment experienced, and/or fibrosis stage >F2 and viremia level >600,000 IU showed SVR (71%) (12 pts of whom 8 were treatment experienced) • P value 0.01 (S)

  11. 0= naïve, Fibrosis <F3, viremial<600,000 IU 1= treatment experienced, and/or fibrosis ≥F3, viremial >600,000 IU

  12. SOF STUDIES 1. Lawitz et al. DDW 2013. 2. Ruane et al. EAS L2014. Poster 1242. 3. Esmat et al,AASLD. 2014 EGYPTIAN

  13. Non invasive detection of hepatic fibrosis Fib-4 Formula http://gihep.com/calculators/hepatology/fibrosis-4-score/

  14. Non invasive detection of hepatic fibrosis Fibroscan

  15. Non invasive diagnosis of Advanced hepatic fibrosis(>F2) *National Committee for control of viral hepatitis, NNTC data , Jan 2014 ♠ Esmat et al, Arab Journal of Gastroenterology 14 (2013) 109–112

  16. PEARL 1 INTERFERON-FREE REGIMENS OF ABT-450/R + ABT-267 WITH OR WITHOUT RIBAVIRIN In 135 Ch HCV GENOTYPE 4 Patients Treatment-naive and Peginterferon/RBV-experienced patients with chronic HCV GT4 infection were enrolled. Treatment-naive patients received ABT-450/r (150/100mg QD) + ABT-267 (25mg QD) ± weight-based RBV for 12 weeks. Experienced patients received the RBV-containing regimen for 12 weeks. Hezode EASL 2014 Ab 58

  17. Current and future regimens containing the new DAAs for genotype 4 patients Phase III Phase IIb Experienced Experienced Naive Experienced Naive Naive Naive Experienced Naive Naive Experienced 100 100 No data for DCV/PR SVR (%) 12/12 12/12 10/17 27/28 14/14 13/15 11/14 42/42 37/37 29/35 41/72 SOF/RBV2 12 wk SOF/PR1NEUTRINO SOF/RBV2 24 wk ABT-450/r + Ombitasvir +RBV*4 PEARL-I (SVR4 only in experienced) DCV 60 mg/PR*5COMMAND-1 SMV/PR*3RESTORE 1. Lawitz et al. DDW 2013. 2. Ruane et al. EAS L2014. Poster 1242. 3. Moreno et al. EASL 2014. Poster 1319. 4.Hézode et al.EASL2014. 4. Hézode et al. AASLD 2012. Poster 755.

  18. EASL Guidelines: Treatment of HCV GT 4 infection

  19. COST EFFECTIVENESS CHART 120,000 L.E SVR % 12,000 L.E 9600 L.E 12,600 L.E 6600 L.E COST/PT *NAÏVE, NON CIRRHOTIC, LOW VIREMIA,

  20. Eradication of HCV in EgyptOvercoming the Barriers

  21. Annual mortality assumed at: 50/100,000 Or 5/1000 for HCV positive patients

  22. Annual mortality assumed at: 50/100,000 Or 5/1000 for HCV positive patients

  23. Overcome the Barriers • Ideal drug • Decrease incidence • Mass treatment

  24. Ideal Drug It is important for patients treatment but more important for control and eradication of any infectious disease

  25. Decrease incidence • Blood safety. • Avoid unneeded injection. • Auto destructive syringes. • Infection control. • Media awareness. • Case detection and treatment by Ideal drug

  26. HCV in EGYPTfrom Control to Eradication To decrease HCV prevalence to< 2 % in Egypt in 10 years(Mathematical modeling) Effective treatment SVR > 90% Annual treatment of 250.000 to 300.000 patients Decrease incidence by prioritize treatment to most frequent injectors J.viral hepatitis,2014

  27. HCV Treatment guidelines(Draft)

  28. Priority for treatment will be directed towards patients with F3 and F4. • No differentiation in treatment priority will be established based on the previous treatment experience.

  29. Assessment of fibrosis stage will be performed by using a combination of both Fibroscan results and FIB 4 score. F3-4 stage will be considered if both Fibroscan result is more than 9.5 and FIB4 score is more than 1.45. If both results are below these cut-off values, patient will not be assigned as a treatment priority . If one of these two methods is above the cut-off value while the other is below, performing liver biopsy or re-assessment after one year is recommended to rule out the fibrosis stage of the patient.

  30. Upper GI endoscopy is mandatory in the following circumstances: a. Histological evidence of cirrhosis by liver biopsy b. Fibroscan > 19.2 K.Pa c. Platelet count < 100,000

  31. Patients who are eligible to receive Interferon (according to the currently used inclusion/exclusion criteria for combined IFN/RBV treatment)will be treated with daily Sofosbuvir (400 mg) and weight-based RBV (1000 mg [<75 kg] to 1200 mg [>75 kg]) plus weekly PEG for 12 weeks. • Recommended regimen for patients who are not eligible to receive IFN is daily Sofosbuvir (400 mg) plus weight-based RBV (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 24 weeks

  32. Inclusion criteria for treatment will be expanded to adapt for more advanced liver fibrosis patients (who will be treated with Interferon free regimen) as defined with the presence of one or more of the following; • Child score up to 8 • Total bilirubin ≤ 3 • Albumin ≥ 2.5 • Platelet count ≥ 50,000 • Prtothrombin concentration ≥ 50% • Hemoglobin concentration ≥ 10 mg • Otherwise, waiting for new DAAs combination is advised.

  33. Patients with more decompensated liver disease will be excluded from treatment until enough data will be available and this will be applied to: • Child C patients with scores ≥ 9 • Presence of ascites (except after control) • Patients with HCC except after successful radical curative intervention (4 months after resection or successful local ablation) evident by triphasic CT. • Presence of large risky esophageal varices (except after prophylactic management)

  34. Age limits for treatment legibility will be above 18 years and below 70 years for all patients while BMI will be accepted up to 35. • The same rules will be applied for all patients regardless the source of payment and there will be no role for patients' preferences in deciding the treatment regimen.

  35. For special population groups; priority for treatment will be offered for post liver transplantation, post kidney transplantation patients and combined HCV/HBV infection regardless the fibrosis stage • . Other groups like Pediatric age group and kidney disease patients will be kept for discussion after the availability of enough data.

  36. Patients with documented extra-hepatic manifestations will be prioritized for treatment according to the same guidelines. • Treatment experienced patients should not start evaluation for new treatment regimens except after 6 months from cessation of interferon therapy.

  37. Gamal Esmat

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