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Recent HCV treatment developments: In pursuit of perfectovir

Recent HCV treatment developments: In pursuit of perfectovir. Professor Greg Dore Kirby Institute, UNSW Australia; & St Vincent’s Hospital, Sydney. HCV treatment strategies: Australia. PEG-IFN + RBV. PEG-IFN + RBV + DAA. Treatment complexity. IFN-free DAA combination. 2011.

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Recent HCV treatment developments: In pursuit of perfectovir

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  1. Recent HCV treatment developments:In pursuit of perfectovir Professor Greg Dore Kirby Institute, UNSW Australia; & St Vincent’s Hospital, Sydney

  2. HCV treatment strategies: Australia PEG-IFN + RBV PEG-IFN + RBV + DAA Treatment complexity IFN-free DAA combination 2011 2012 2013 2014 2015 2016 Dore GJ. MJA 2012 (revised)

  3. HCV treatment strategies: United States PEG-IFN + RBV PEG-IFN + RBV + DAA Treatment complexity IFN-free DAA combination 2011 2012 2013 2014 2015 2016 Dore GJ. MJA 2012 (revised)

  4. HCV life cycle Liang TJ & Ghany MG. NEJM 2013;368:1907-1917

  5. HCV therapeutic development X X ? Welsch & Zeuzum. Gastroenterology 2012;142:1351-1355

  6. Key recent HCV therapeutic development findings: • Sofosbuvir (nucleotide analogue) and Simeprevir (protease inhibitor) licensure for GT1 has revealed the future = IFN-free dual DAA short duration therapy (12 weeks) • Several highly curative GT1 IFN-free DAA regimens will be available • HCV GT3 therapeutic solution less advanced, but pangenotypic regimens likely • HIV does not impair response to IFN-free DAA therapy • HCV resistance will not be a major clinical issue • Ultimately limited individualisation required

  7. HCV therapeutic development Key attributes of perfectovir • Extremely high efficacy (>95%) • Minimal toxicity • Once daily dosing • Pangenotypic • Short duration (4-6 weeks)

  8. HCV therapeutic development Key attributes of perfectovir • Extremely high efficacy (>95%) • Minimal toxicity • Once daily dosing • Pangenotypic • Short duration (4-6 weeks)

  9. NEUTRINO: PEG-IFN/RBV/Sofosbuvir • Genotype 1 (+4/5/6) treatment naïve, 12 weeks SVR12 % Lawitz E et al. NEJM 2013;368:1878-1887

  10. Abbvie: ABT-450/r/Ombitasvir/Dasabuvir • Genotype 1, treatment naïve and experienced SVR12 % Sapphire-I & II Pearl-IV & Turquoise-II Pearl-II & III Zeuzem S, et al. NEJM 2014;370:1604-1614; Poordad F, et al. NEJM 2014; Feld JJ, et al. NEJM 2014

  11. Gilead: Sofosbuvir/Ledipasvir • Genotype 1, treatment naive and experienced SVR 12 % ION-1 (16% cirrhosis) ION-2 (20% cirrhosis) ION-3 Afdhal N, et al. NEJM 2014;370:1483-1493; Afdhal N, et al. NEJM 2014; Kowdley KV, et al. NEJM 2014

  12. COSMOS: Sofosbuvir/Simeprevir • Genotype 1, treatment naive and experienced, 12 weeks SVR 12 % Jacobson I, et al. AASLD 2013

  13. Sofosbuvir/Ribavirin vs PEG-IFN/RBV • Genotype 2, treatment naive, 12 weeks vs 24 weeks SVR 12 % Lawitz E et al. NEJM 2013;368:1878-1887

  14. Sofosbuvir/Ribavirin • Genotype 3, treatment naïve and experienced, 24 weeks SVR 12 % Zeuzem S et al, AASLD 2013

  15. HCV therapeutic development Key attributes of perfectovir • Extremely high efficacy (>95%) • Minimal toxicity • Once daily dosing • Pangenotypic • Short duration (4-6 weeks)

  16. HCV prevalence and genotype distribution Hajarizadeh B, Grebely J, Dore GJ. Nat Rev GastroenterolHepatol 2013

  17. Sofosbuvir/GS-5816 • Treatment naïve, F0-3, 12 weeks SVR12 % Everson GT, et al. ILC2014

  18. HCV therapeutic development Key attributes of perfectovir • Extremely high efficacy (>95%) • Minimal toxicity • Once daily dosing • Pangenotypic • Short duration (4-6 weeks)

  19. Sofosbuvir/Ledipasvir • Genotype 1, treatment naïve, F0-2 SVR 12 % Lawitz E et al, AASLD 2013; Gane E et al, AASLD 2013

  20. Sofosbuvir/Ledipasvir • Genotype 1, treatment naïve, F0-2 SVR 12 % Lawitz E et al, AASLD 2013; Gane E et al, AASLD 2013

  21. Sofosbuvir/Ledipasvir • Genotype 1, treatment naïve, F0-2 SVR 12 % Lawitz E et al, AASLD 2013; Gane E et al, AASLD 2013

  22. Sofosbuvir/Ledipasvir/3rdDAA • Genotype 1, treatment naïve, F0-3 SVR 12 % Kohli A et al, AASLD 2013

  23. Sofosbuvir/Ledipasvir/3rdDAA • Genotype 1, treatment naïve, F0-3 SVR12 % Kohli A et al, AASLD 2013

  24. HCV regimen approval timelines: Australia

  25. HCV regimen approval timelines: Australia PEG + RBV + TPV/BCP PEG + RBV 2014 2015 2016 2017 2018 2019 2020

  26. HCV regimen approval timelines: Australia TGA PBAC IFN-free: Sofosbuvir + Ribavirin (G2/3) TGA PBAC PEG + RBV + Sofosbuvir / Simeprevir (G1) PEG + RBV + TPV/BCP PEG + RBV 2014 2015 2016 2017 2018 2019 2020

  27. HCV regimen approval timelines: Australia TGA PBAC IFN-free: Sofosbuvir + Ledipasvir(G1) TGA PBAC IFN-free: ABT450/r + Ombitasvir + Dasabuvir +/- Ribavirin (G1) TGA PBAC IFN-free: Sofosbuvir + Ribavirin (G2/3) TGA PBAC PEG + RBV + Sofosbuvir / Simeprevir (G1) PEG + RBV + TPV/BCP PEG + RBV 2014 2015 2016 2017 2018 2019 2020

  28. HCV regimen approval timelines: Australia TGA PBAC IFN-free: Sofosbuvir + GS-5816 (GT1-6) TGA PBAC IFN-free: Sofosbuvir + Ledipasvir(G1) TGA PBAC IFN-free: ABT450/r + Ombitasvir + Dasabuvir +/- Ribavirin (G1) TGA PBAC IFN-free: Sofosbuvir + Ribavirin (G2/3) TGA PBAC PEG + RBV + Sofosbuvir / Simeprevir (G1) PEG + RBV + TPV/BCP PEG + RBV 2014 2015 2016 2017 2018 2019 2020

  29. HCV therapeutic development A few caveats • High drug pricing • Probable disease stage restriction for IFN-free DAA therapy • Potential treatment caps But • Several pharma companies should ensure competitive pricing • Ability to cure close to 100% should empower the sector

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