HCV : TRANSFORMING MANAGEMENT IN EGYPT

1. HCV: TRANSFORMING MANAGEMENT IN EGYPT Dr-MOHAMMED EMAM Zagazig university-2014

4. “We're all really excited that for the first time we have curative therapies for hepatitis C which are much more effective than what we had before and much easier to tolerate,“

5. “We think the move away from interferon and toward a high probability of success is remarkably encouraging for all of us.... Suddenly, it's true to think that we can cure most patients with hepatitis C,"

6. WHERE WE ARE NOW?

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12. Sofosbuvir is a game-changer and will allow high cure rates with just 12-week regimens,"

13. sofosbuvir holds numerous advantages over current therapy because of its: -Efficacy profile, -Safety, -Tolerability across many different patient populations and HCV genotypes, -Dosing simplicity. ....

14. INDICATIONS AND USAGE : SOVALDI is Indicated for : -Treatment of chronic hepatitis C (CHC) infection as a part of a combination antiviral treatment regimen.

16. Sofosbuvir and Ribavirin in HCV Genotype 4Egyptian Ancestry Trial: Study Features Source: Ruane P, et al. 49th EASL. April 2014: Abstract P1243.

17. Sofosbuvir and Ribavirin in HCV Genotype 4Egyptian Ancestry Trial: Baseline Characteristics Source: Ruane P, et al. 49th EASL. April 2014: Abstract P1243.

18. Sofosbuvir and Ribavirin in HCV Genotype 4Egyptian Ancestry Trial: Design Week 0 12 24 36 GT 4 Naïveor Experienced Sofosbuvir +RBV(n = 32) SVR12 Sofosbuvir + RBV(n = 28) SVR12 Drug DosingSofosbuvir: 400 mg once dailyWeight-Based Ribavirin (in 2 divided doses): 1000 mg/day if < 75 kg or 1200 mg/day if ≥ 75 kg Source: Ruane P, et al. 49th EASL. April 2014: Abstract P1243.

19. Sofosbuvir and Ribavirin in HCV Genotype 4Egyptian Ancestry Trial: Results SVR 12 by Regimen Duration and Treatment Experience 11/14 14/14 10/17 13/15 Treatment Naive Treatment Experienced Source: RuaneP, et al. 49th EASL. April 2014: Abstract P1243.

20. Phase III NEUTRINO study: 96% SVR12 rate in patients with genotype4 HCV treated with sofosbuvir plus pegIFN/RBV for 12 weeks Current pilot study evaluating sofosbuvir plus RBV in immigrants of full Egyptian ancestry in the US infected with genotype 4 HCV

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23. HCV FREE WORLD

24. NO DREAMS WITHOUT PROBLEMS

25. Guidelines for low and middle income countries Most of the existing guidelines for the treatment of hepatitis C have been developed by specialist medical organizations and relate to the treatment of persons with different genotypes and living in high-income countries. There are no evidence-based treatment guidelines that focus on persons living in low- and middle-income countries. .

26. The suggestive objective of these guidelines These guidelines will provide a framework for the development or strengthening of hepatitis C treatment programmers' in low- and middle-income countries(especially in Egypt) according to evidence-based recommendations on screening for HCV infection, and the care and treatment of persons with HCV infection aiming to achieve a mass treatment in our locality

27. Price of medicines HCV treatment is expensive. Prices range from US$ 5 000 in Egypt for 48-weeks of PEG/IFN RBV to as much as US$84 000 in the US for a single 12-week course of sofosbuvir. At these prices, these treatments will remain unaffordable for most persons who need treatment. A concerted effort is needed to reduce the price of HCV medicines. The experience with HIV, where the price of antiretrovirals was reduced by nearly a hundred fold through the introduction of generic drugs, has shown that the key to achieving low prices for medicines is to use a multipronged approach..

28. key to achieving low prices for medicines :This can include 1- Voluntary licensing (where the patent owner licenses the medicine to generics-producing companies or a patent pool), 2-Tiered pricing (where the manufacturer sets different prices for different countries based on their income level and disease burden), 3-compulsory licensing (where a national government grants a license to companies producing generic drugs or importing the product 4-National governments, international agencies, donors, civil-society organizations, and the pharmaceutical industry will need to work together to help assure that hepatitis C treatment is affordable and accessible for all those who need treatment.

30. The primary goal of HCV therapy is to cure the infection. A sustained virological response (SVR) is defined as undetectable HCV RNA 12 weeks (SVR12) or 24 weeks (SVR24) after treatment completion. The infection is cured in more than 99% of patients who achieve an SVR. The SVR is generally associated with resolution of liver disease in patients without cirrhosis. .

31. Patients with cirrhosis remain at risk of life-threatening complications; however hepatic fibrosis mayregress and the risk of complications such as hepatic failure and portal hypertension is reduced. More data is required to ascertain the lifetime residual risk of hepatocellular carcinoma after viral infection has been eradicated .

32. In addition to pegylated IFN-α and ribavirin, three new HCV DAAs licensed in the first half of 2014, for use as part Of combination therapies for HCV infection. 1-Sofosbuvir,a nucleotide analogue inhibitor of HCV RNA-dependent RNA polymerase, has been approved in January 2014. 2-Simeprevir, a second-wave, first generation NS3/4A protease inhibitor approved in May 2014. 3-Daclatasvir, an NS5A inhibitor, is likely to be approved in August or September 2014. Other drugs may be approved later in 2014 or in 2015.

33. Who should be treated? All treatment-naïve and -experienced patients with compensated disease due to HCV should be considered for therapy (Recommendation A1) • Treatment should be prioritized for patients with significant fibrosis (METAVIR score F3 to F4) (Recommendation A1) • Treatment is justified in patients with moderate fibrosis (METAVIR score F2) (Recommendation A2)

34. • In patients with no or mild disease (METAVIR score F0-F1), the indication for and timing of therapy can be individualized. • Patients with decompensated cirrhosis who are on the transplant list should be considered for IFN-free, ideally ribavirin-free therapy

35. Available drugs (approved by before the end of 2014 Pegylated IFN-α2a should be used at the dose of 180 μg/week, whereas pegylated IFN-α2b should be used at the weight-based dose of 1.5 μg/kg/week. Ribavirin dose should be 1000 or 1200 mg/ day, based on body weight (<75 kg or ≥75 kg, respectively). Sofosbuvir should be administered at the dose of 400 mg (one tablet).

36. Sofosbuvirshould be administered at the dose of 400 mg (one tablet) Once per day., No dose recommendation can be given for patients with severe renal impairment (estimated glomerular filtration rate <30 ml/min/1.73m2) or with end-stage renal disease due to higher exposures (up to 20-fold) of the predominant sofosbuvir metabolite. .

37. Sofosbuvir. Sofosbuvir is well tolerated over 12 to 24 weeks of administration. The most common adverse events (≥20%) observed in combination with ribavirin were fatigue and headache. The most common adverse events (≥20%) observed in combination with pegylated IFN-α and ribavirin were fatigue ,headache, nausea, insomnia, and anaemia.

38. Simeprevir should be administered at the dose of 150 mg (one capsule) once per day. No dose recommendation can be Given for patients with Child-Pugh Class B or C cirrhosis, due to Higher simeprevir exposures (particularly in Child-Pugh C patients) that may be associated with increased frequency of adverse reactions. .

39. Simeprevir. is well tolerated. Adverse reactions With at least 3%higher frequency in patients receiving simeprevir in Combination with pegylated IFN-α and ribavirin were rash(including photosensitivity), pruritus and nausea. Because simeprevir is an inhibitor of the transporters ( MRP2,) mild, transient Hyper bilirubinaemia not accompanied by changes in other liver parameters was observed in 10% of cases.

40. Daclatasvirshould be administered at the dose of 60 mg (one tablet) once per day. It is overall well tolerated. Dose adjustments are not needed in patients with Child B or C disease. The most frequently reported side effects with daclatasvir were fatigue, headache, and nausea. Little information has been released on daclatasvir drug-drug interactions.

41. 2014 Treatment of chronic hepatitis C -G4 Broad choice of drug combinations

42. 2014 Genotype 4 , 6 Options

43. Genotype 4 , Option 1

44. Genotype 4 , Option 1 Comments: This combination has been evaluated in the NEUTRINO Phase III trial in treatment-naïve patients The SVR rate in genotype 4 patients was 96% . Whether longer treatment duration would be needed in the most difficult-to-treat population is unknown

45. Genotype 4 , Option 2

46. Genotype 4 , Option 2 Comments: Indeed, SVR was achieved in 89% (31/35) of treatment-naïve patients, 86% (19/22) of prior relapsers, 100% (10/10) of prior partial responders, and 75%, (30/40) of prior null responders.

47. Genotype 4 , Option 3

48. Genotype 4 , Option 3 Comments: Although this combination is theoretically effective, few data is available. The SVR rate was 100% (12/12) in the COMMAND-1 trial

49. Genotype 4 , Option 4

50. Genotype 4 , Option 4 Comment: Only preliminary data is available (SVR at week 4 post-treatment) in a small number of American patients of Egyptian ancestry The preliminary SVR rates were 79% (11/14) and 100% (14/14) after 12 and 24 weeks of treatment, respectively, in treatment-naïve patients, and 59% (10/17) and 93% (14/15) after 12 and 24 weeks, respectively, in treatment-experienced patients